- Email: [email protected]
Corticosteroids as potential mechanism regulating variability in reproductive success in monogamous oldfield mice (Peromyscus polionotus)
Physiology & Behavior 86 (2005) 96 – 102
Corticosteroids as potential mechanism regulating variability in reproductive success in monogamous oldfield mice (Peromyscus polionotus) Tatjana C. Good *, Kendra K. Harris, Chioma A. Ihunnah Department of Ecology and Evolutionary Biology, Princeton University, USA Received 26 May 2005; accepted 24 June 2005
Abstract Male and female mammals undergo profound hormonal changes during pregnancy, some of which are sufficiently dramatic to influence offspring survival. In order to understand the proximate mechanisms regulating the variability in reproductive success within and between individuals, we monitored changes in fecal corticosteroid concentrations over the reproductive cycle in male and female oldfield mice (Peromyscus polionotus subgriseus) to test whether corticosteroid concentrations during pregnancy were associated with offspring survival. In females that successfully raised litters to weaning, fecal corticosteroid concentrations were low until mid-gestation and increased significantly towards term; in females that did not raise their pups to weaning, fecal corticosteroid concentrations were significantly higher at mid-gestation, and remained high until late gestation. The difference in fecal corticosteroid concentrations at mid-gestation between successful and unsuccessful females can be explained by the fact that successful females were lactating. Lactation has been associated with a down-regulation of the hypothalamic – pituitary – adrenal (HPA) axis and, accordingly, a decrease in plasma corticosterone (CORT) in several species, including humans. Males that successfully raised their litters had low fecal corticosteroid concentrations throughout their partner’s pregnancy. Unsuccessful males, however, had significantly higher fecal corticosteroid concentrations at term than males that raised their pups to weaning. While these preliminary data require further investigation, we suggest that pre-partum fecal corticosteroid concentrations in males were responsible for the variability in reproductive success. D 2005 Elsevier Inc. All rights reserved. Keywords: Cannibalism; Fecal corticosteroids; Gestation; Hypothalamic – pituitary – adrenal axis (HPA); Infanticide; Paternal behavior; Pregnancy; Offspring survival; Oxytocin (OT)
1. Introduction Natural changes in the hypothalamic –pituitary – adrenal (HPA) axis in female mammals during pregnancy are well documented [9,25,51] and increases in corticosterone (CORT) near term are essential for the normal development of the fetus [18,33]. During rodent pregnancies, CORT
* Corresponding author. Centro de Ecologı´a Instituto Venezolano de Investigaciones Cientı´ficas, Apdo. 21827, Caracas 1020-A, Venezuela. Tel.: +58 212 504 1886; fax: +58 212 504 1197. E-mail address: [email protected] (T.C. Good). 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.06.030
concentrations typically increase from mid-gestation onwards, then drop dramatically at term [2,15,17,49]. The increase in maternal plasma CORT concentrations is most likely triggered by increasing metabolic demands of the pregnancy [22]. This increase in CORT secretion towards the end of pregnancy has several different functions: (1) it is essential for the maturation of several organs in the fetus, especially the lung and gut [18,33], (2) it plays a role in the onset of parturition (reviewed in Ref [25]) and (3) it is critical for the initiation and maintenance of lactation [10,41] at the end of pregnancy. However, the HPA axis can also exert multiple inhibitory effects on the female reproductive system when activated by
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
excessive stressors [51]. Glucocorticoids secreted from the adrenal cortex act at the levels of the hypothalamic, pituitary and gonadal tissues to suppress the gonadal axis [9], which can lead to adverse effects on reproductive functions (ovarian cyclicity, embryo development, neonatal weight, litter size, etc. [23]). Prenatal stress studies have demonstrated that high concentrations of CORT at specific times of the pregnancy can also have detrimental effects on the offspring (e.g. growth rates and memory: [27]). Glucocorticoids can also affect changes in parenting behaviors: stress during pregnancy has been demonstrated to decrease nurturing/nesting behaviors and pup retrieval in Swiss Webster mice [32]. Changes in corticosteroid concentrations may even play a role in mediating infanticidal and/or cannibalistic behavior [35]. With the recent development of non-invasive endocrine techniques such as the measurement of fecal steroids [19,50,52], it is now possible to monitor corticosteroid concentrations over the reproductive cycle of females without introducing artificial stress into the sampling procedure. In this study, we monitored fecal corticosteroid concentrations in male and female oldfield mice (Peromyscus polionotus subgriseus) over the female’s reproductive cycle to examine whether fecal corticosteroid concentrations could be regulating variability in reproductive success in these mice. Oldfield mice are socially and reproductively monogamous, mate for life and raise several litters together [14]. Furthermore, males and females exhibit extensive parental care in captivity [28,39]. Studies of naturally paternal species have demonstrated that hormones play a role in the onset and maintenance of male parental behavior [reviewed in Refs. [54] and [55]]. Particularly in species that form monogamous pair bonds, endocrinological changes in the male occur when cohabitating with the female [4,5,20,21,43]. However, the relationship between glucocorticosteroids and paternal care is not yet clear. Changes in cortisol concentrations before and after the birth of a litter did not differ between the biparental Djungarian hamster (P. campbelli) and the uniparental Siberian dwarf hamster (P. sungorus, [37]). In cotton-top tamarins (Saguinus oedipus), males showed an increase in urinary glucocorticosteroid concentrations possibly in response to the midpregnancy rise in glucocorticoids in females. This signal could potentially activate other hormonal changes in males to prepare them for their parenting role [56]. In men, cortisol concentrations also increased before births [43]. Elevated cortisol in men during late pregnancy and labor may help new fathers become attached to their newborns, as was shown for new mothers [13]. We hypothesized that fecal corticosteroid concentrations during the oldfield mouse pregnancy would differ between pairs that successfully raised all their litters to weaning and those pairs that never managed to raise pups. Based on the well-known temporal pattern of CORT during pregnancy in rodents, we predicted that successful females would
97
have lower corticosteroid concentrations than unsuccessful females until late gestation. Furthermore, we predicted that successful males would have higher corticosteroid concentrations than unsuccessful males during the latter half of their partners’ pregnancy in preparation for their parenting role.
2. Methods 2.1. Animals A total of 10 pairs of mice were used for this study. Pairs were housed together for 120 days, which corresponds to the average adult life expectancy in the field [36]. Animal care is explained in detail in Ref. [19]. All pups were raised with both parents and weaned by the experimenter at 20 days of age. ‘‘Successful’’ pairs (n = 4) were pairs that successfully raised four consecutive litters to weaning (20 days of age). ‘‘Unsuccessful’’ pairs never managed to raise pups to weaning (n = 4). Two pairs failed to raise their first litter, but eventually managed to raise the subsequent three litters (‘‘mixed-success’’ pairs). Births usually occur during the early daylight hours [26]. Pups were counted on the day of birth. Litters of unsuccessful pairs were all cannibalized within 24 h of birth. The parent responsible for the infanticide and/or cannibalism was unknown. 2.2. Fecal sample collection In order to minimize disturbance of the pair during the female’s pregnancy, we collected fecal samples rather than blood samples to monitor changes in corticosteroid concentrations in males and females through time. To avoid triggering any human-related cannibalism, sample collection began the day after the birth of the second litter and was never carried out on the day of birth of any litter. For 8 of 10 pairs, samples were collected during two consecutive gestation periods, beginning the day after the birth of the second litter until the birth of the fourth litter. For these pair, daily corticosteroid concentrations were averaged across the two gestation periods. For two pairs (one reproductively successful and one mixed-success pair), a complete set of fecal samples were available for the third gestation period only. Samples were collected daily between 8 and 10 am to avoid diel variations in corticosteroid concentrations [19]. Fecal samples were collected by holding the mice briefly in one hand and catching the pellets in a micro-centrifuge tube as they fell while avoiding urine contamination. Fecal samples were then stored in micro-centrifuge tubes at 20 -C until extraction. All animals were used to being handled daily since they were weaned. Therefore, we believe that the effect of restraint stress on corticosteroid concentrations during this study is negligible.
98
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
2.3. Fecal corticosteroid analysis
3. Results
All samples were assayed in duplicate at one-half volume by using a double-anti-body 125I-radioimmunoassay kit (ICN Pharmaceuticals, Costa Mesa, Calif.; catalog no. 07120102 for corticosterone) and counted on a Hewlett Packard Cobra II Auto Gamma Counter. Fecal samples were diluted 1:5 in the assay buffer prior to radioimmunoassay. Detailed information on fecal extraction and assay procedures are given elsewhere [19]. Intra- and inter-assay coefficient of variation was 7.4% and 18.5% for the low concentration fecal pool, and 7.6% and 14.0% for the high concentration fecal pool (n = 26). We ascertained that there was equal representation of different individuals and time points across assays. Corticosteroid concentrations are expressed as nanograms of hormone per gram of fecal matter.
3.1. Latency to birth of first litter, gestation period and number of pups born
2.4. Data analysis
3.2. Changes in corticosteroid concentrations in females
The gestation period was divided into three distinct time periods that reflect changes in circulating maternal CORT concentrations in the mouse: early gestation: days 1 – 10 (little CORT production by mother), mid-gestation: days 11– 15 (increased CORT production by mother) and late gestation: days 16– 19 (substantial CORT production by fetuses [2]). Due to their postpartum estrus, females conceive the day they give birth. Therefore, interbirth interval is equal to gestation period in this species. In oldfield mice, the mean gestation period is 23.8 days for non-lactating females and 28 days for lactating females [26]. Furthermore, the variability in gestation period is larger in the lactating females than in non-lactating females (see [45]) and is probably due to the competing energetic demands on the mother by the developing fetuses and nursing pups. To calculate the ‘‘trimester’’ lengths for females with different gestation periods, we divided each gestation period in proportion to the ‘‘trimester’’ lengths for a 19 day mouse gestation described above. All data were analyzed using the SPSS for Windows statistical package (Version 10.0.5). Differences in latency to birth of first litter, gestation period, number of pups born, and corticosteroid concentrations between successful and unsuccessful individuals were compared with Mann – Whitney U test. Due to the non-normality of errors introduced by limited sample sizes, we were unable to use a mixed between – within ANOVA to statistically evaluate the differences between successful and unsuccessful individuals across the three time periods. Unfortunately, there is no non-parametric equivalent to this test. Rather, changes in the temporal pattern of corticosteroid concentration across those three time periods were tested using the non-parametric equivalent of one-way repeated measures ANOVA (Friedman test). Tukey HSD post-hoc tests were conducted to determine differences between time periods within groups. P-values of less than 0.05 were considered significant.
Corticosteroid concentrations of the second and third successful pregnancies of the mixed-success females followed the same temporal pattern as those of successful females and were therefore pooled with the successful females for further analyses.
Successful pairs did not differ from unsuccessful pairs in latency to birth of first litter (Fig. 1A; U = 7.5; p = 0.89). However, raising a litter successfully to weaning affected the length of the gestation period of the next litter. The average gestation period of females that successfully raised their pups to weaning was significantly longer that that of females that did not raise their litters to weaning (Fig. 1B; U = 0; p = 0.03). The number of pups born in litters 1– 4 did not differ between successful and unsuccessful pairs (Fig. 2; U = 7.0; p = 0.89).
A
Latency to birth of first litter
35 30 25 20 15 10 5 0
B
successful
35
*
30
Gestation period
unsuccessful
25 20 15 10 5 0
successful
unsuccessful
Fig. 1. (A) Latency (+STDEV) to birth of first litter and (B) gestation period (+STDEV) for litters 2 – 4 in successful (n = 4) and unsuccessful (n = 4) pairs. *p < 0.05.
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102 6
difference between successful and unsuccessful females with respect to latency to birth of first litter or number of pups born. This suggests that there is no inherent difference in the ability of females to conceive or maintain a pregnancy. Successful (i.e. lactating) females had a longer gestation period than unsuccessful (i.e. non-lactating) females, which stands in agreement with Layne [26].
5 4 3 2
4.1. Changes in corticosteroid concentrations during pregnancy in the females
0
successful
unsuccessful
Fig. 2. Number of pups (+STDEV) born across all litters in successful (n = 4) and unsuccessful (n = 4) pairs.
There was a significant change in fecal corticosteroid concentrations across the three time periods for both successful (Friedman’s test: F (2, 23) = 5.01, p = 0.016) and unsuccessful (Friedman’s test: F (2, 20) = 11.31, p = 0.001) females. However, the increase in corticosteroid concentrations occurred at different times: There was a significant increase between mid- and late gestation (Tukey HSD test: p = 0.016) in successful females, whereas the significant increase in corticosteroid concentrations in unsuccessful females occurred between early and mid-gestation (Tukey HSD test: p = 0.009). Fecal corticosteroid concentrations did not differ significantly between successful and unsuccessful females at early (Fig. 3A; U = 78.0; p = 0.76) or late gestation (U = 11.0; p = 0.91). Fecal corticosteroid concentrations of unsuccessful females were significantly higher than those of successful and mixed-success females combined at midgestation (Fig. 3A; U = 1.0; p = 0.001). 3.3. Changes in corticosteroid concentrations in males There was no significant change in fecal corticosteroid concentration across the three time periods in successful (Friedman’s test: F (2, 23) = 2.39; p = 0.1) or in unsuccessful males (Friedman’s test: F (2, 20) = 0.56; p = 0.6). Fecal corticosteroid concentrations did not differ significantly between successful and unsuccessful males at early (Fig. 3B; U = 59.0; p = 0.32) or mid-gestation (U = 28.0; p = 0.88). However, fecal corticosteroid concentrations in unsuccessful males were significantly higher than in successful males at late gestation (Fig. 3B; U = 0; p = 0.01).
4. Discussion In this study, we monitored changes in fecal corticosteroid concentrations over the reproductive cycle in male and female oldfield mice (Peromyscus polionotus) to test whether corticosteroid concentrations during pregnancy were associated with offspring survival. There was no
In our study, successful and unsuccessful females did not differ in their corticosteroid concentrations in early gestation. Studies on rodent fetal organogenesis [38,47] and on the expression of genes responsible for the production of
A 140
Corticosteroid concentrations [ng/g]
1
120
successful females (n=6) unsuccessful females (n=4)
*
100 80 60 40 20 0 early
mid
late
Gestation
B 140
Corticosteroid concentrations [ng/g]
Number of pups born
99
120
successful males (n=6) unsuccessful males (n=4)
*
100 80 60 40 20 0 early
mid
late
Gestation Fig. 3. Fecal corticosteroid concentrations (+STDEV) throughout gestation in (A) females and (B) males. Note that corticosteroid concentrations for individuals with two gestation periods were averaged for each of the three time periods. *p < 0.05. (A) Successful (dark bars, n = 6) and unsuccessful (light bars, n = 4) females. Note that mixed-success females were added to the reproductively successful females for these analyses. (B) Successful (dark bars, n = 6) and unsuccessful (light bars, n = 4) males. Note that mixed-success males were added to the reproductively successful males for these analyses. High corticosteroid concentrations at term were associated with the loss of the litter immediately after parturition.
100
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
hormones along the HPA axis in the fetus [3,6,24,42,48] have demonstrated that circulating plasma CORT in early gestation is solely of maternal origin. Since early lactation is not yet energetically demanding [30,40], we did not expect differences in corticosteroid concentrations between successful and unsuccessful females at this time. Studies investigating adrenalectomy at various stages of the pregnancy [2,7] have demonstrated that the fetus produces much of the circulating CORT near term. In fact, the human fetus is responsible for at least two thirds of maternal plasma CORT concentrations at term [11]. The lack of significant difference in corticosteroid concentrations between successful and unsuccessful females at term can be explained by the fact that the majority of circulating maternal plasma CORT at this time is produced by the pups and that successful and unsuccessful females did not differ in the number of pups born. At mid-gestation, circulating CORT in mice is of maternal origin [2]. In our study, unsuccessful females had significantly higher corticosteroid concentrations at midgestation than successful females. Successful and unsuccessful females differed in one physiological condition: lactation. Successful females were simultaneously pregnant and lactating, whereas unsuccessful females were never lactating. During lactation, the HPA axis is down-regulated in several species, including humans [1,53], which could explain why corticosteroid concentrations in successful females were significantly lower than those of unsuccessful females. The HPA axis could be inhibited by oxytocin (OT), the hormone responsible for the stimulation of milk ejection during lactation [8,34,46].
previously presumed in mediating infanticidal behavior. However, there are alternative explanations for the observed patterns of increased corticosteroid concentration in the unsuccessful males at term: (1) corticosterone could indicate some other quality of the pairs, such as the ability to form pair bonds [37,43,56], and may only be indirectly related to infanticide; (2) changes in corticosterone concentrations in the males could trigger the release of other hormones, that in turn trigger infanticide. Detailed observation of parental behavior during gestation as well as during the first 24 h after parturition, and the monitoring of additional hormones such as prolactin [20], estrogen [12] or testosterone [31] throughout the female’s pregnancy in males and females would be necessary to determine the relationship between hormonal changes, parental behaviors and the resulting consequences for offspring survival.
4.2. Changes in corticosteroid concentrations during pregnancy in the males
Acknowledgments
In males of biparental mammalian species, paternal behavior is associated with changes in hormone concentrations over the reproductive cycle [54,55]. In oldfield mice, successful and unsuccessful males did not differ in corticosteroid concentrations until late gestation. Rather than triggering the onset of other hormonal changes in males to prepare them for their role in parenting, such as was found in male cotton-top tamarins [56] and men [43], high corticosteroid concentrations at term were associated with the loss of the litter. While most of the literature on the proximate mechanisms for the expression and inhibition of infanticide has focused on androgens, testosterone in particular [16,44], little research has been done on the effects of the HPA axis on infanticidal behavior. Available results are conflicting: while McCarthy et al. [29] reported that infanticidal behavior was not influenced by adrenalectomy in sexually inexperienced, adult female mice, Poley [35] demonstrated that cannibalistic females were more prone to auditory stress than non-cannibalistic ones. We hypothesize that corticosteroid concentrations may indeed play a bigger role than
4.3. Concluding remarks We were able to confirm the well-known patterns of corticosterone in females during lactation despite the limitations of small sample size and the choice of statistical analyses in this study. Therefore, we believe that the detected patterns of corticosteroid concentrations in males reflect true changes in the males’ physiology. These results therefore suggest a potential role of the HPA axis in infanticidal behavior. Clearly, this raises myriad new hypotheses, which should stimulate further research in this area.
Jeanne Altmann, Michaela Hau, Henry Horn, Memuna Khan, Lynn Martin, Martin Wikelski and three anonymous reviewers provided excellent comments on the manuscript. Ariana Renick assisted in many aspects of the lab work. Support was provided by the Princeton University, the Animal Behavior Society and the Society for Integrative and Comparative Biology to TCG and by a Mellon Summer Research Fellowship to KKH and CAI.
References [1] Amico JA, Johnston JM, Vagnucci AH. Suckling-induced attenuation of plasma cortisol concentrations in postpartum lactating women. Endocr Rev 1994;20:79 – 87. [2] Barlow SM, Morrison PJ, Sullivan FM. Plasma corticosterone levels during pregnancy in the mouse: the relative contributions of the adrenal glands and foeto – placental units. J Endocrinol 1974; 60:473 – 83. [3] Boudouresque F, Guillaume V, Grino M, Strbak V, Chautard T, ConteDevolx B, et al. Maturation of the pituitary – adrenal function in rat fetuses. Neuroendocrinology 1988;48:417 – 22. [4] Brown RE, Moger WH. Hormonal correlates of parental behavior in male rats. Horm Behav 1983;17:356 – 65.
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102 [5] Brown RE, Murdoch T, Murphy PR, Moger WH. Hormonal responses of male gerbils to stimuli from their mate and pups. Horm Behav 1995;29:474 – 91. [6] Bugnon C, Fellmann D, Gouget A, Cardot J. Ontogeny of the corticoliberin neuroglandular system in the rat brain. Nature 1982;298: 159 – 61. [7] Chatelain A, Dupouy JP, Allaume P. Fetal – maternal adrenocorticotropin and corticosterone relationships in the rat: effects of maternal adrenalectomy. Endocrinology 1980;106:1297 – 303. [8] Chiodera P, Salvarani C, Bacchi MA, Spallanzani R, Cigarini C, Gardini E, et al. Relationship between plasma profiles of oxytocin and adrenocorticotropin hormone during suckling or breast stimulation in women. Horm Res 1991;35:119 – 23. [9] Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic – pituitary – adrenal axis and the female reproductive system: clinical implication. Ann Intern Med 1998;129:229 – 40. [10] De Greef WJ, Van der Schoot P. Effect of adrenalectomy on the regulation of ovarian function during lactation. J Endocrinol 1983; 98:233 – 40. [11] Fencl MD, Stillman RJ, Cohen J, Tulchinsky D. Direct evidence of sudden rise in fetal corticoids late in human gestation. Nature 1980; 287:225 – 6. [12] Fite JE, French JA. Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is there a link with infant survivorship and maternal behavior? Horm Behav 2000;38:1 – 12. [13] Fleming AS, Ruble D, Krieger H, Wong PY. Hormonal and experiential correlates of maternal responsiveness during pregnancy and the puerperium in human mothers. Horm Behav 1997;31: 145 – 58. [14] Foltz DW. Genetic evidence for long-term monogamy in a small rodent, Peromyscus polionotus. Am Nat 1981;117:665 – 75. [15] Gala RR, Westphal U. Corticosteroid-binding activity in serum of mouse, rabbit and guinea pig during pregnancy and lactation: possible involvement in the initiation of lactation. Acta Endocrinol 1967;55: 47 – 61. [16] Gandelman R. Hormones and infanticide. In: Svare BB, editor. Hormones and aggressive behavior. New York’ Plenum Press; 1983. p. 105 – 18. [17] Garland HO, Atherton JC, Baylis C, Moran MRA, Milne CM. Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies. J Endocrinol 1987;113:435 – 44. [18] Gartner H, Graul MC, Oesterreicher TJ, Finegold MJ, Henning SJ. Development of the fetal intestine in mice lacking the glucocorticoid receptor (GR). J Cell Physiol 2002;194:80 – 7. [19] Good T, Khan MZ, Lynch JW. Biochemical and physiological validation of a corticosteroid radioimmunoassay for plasma and fecal samples in oldfield mice (Peromyscus polionotus). Physiol Behav 2003;80:405 – 11. [20] Gubernick DJ, Nelson RJ. Prolactin and paternal behavior in the biparental California mouse, Peromyscus californicus. Horm Behav 1989;23:203 – 10. [21] Gubernick DJ, Winslow JT, Jensen P, Jeanotte L, Bowen J. Oxytocin changes in males over the reproductive cycle in the monogamous, biparental California mouse Peromyscus californicus. Horm Behav 1995;29:59 – 73. [22] Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia’ W.B. Saunders Company; 2000. [23] Herrenkohl LR. Prenatal stress reduces fertility and fecundity in female offspring. Science 1979;206:1097 – 9. [24] Keegan CE, Herman JP, Karolyi J, O’Shea KS, Camper SA, Seasholtz AF. Differential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain. Endocrinology 1994;134: 2547 – 55. [25] Keller-Wood ME, Wood CE. Pituitary – adrenal physiology during pregnancy. Endocrinologist 2001;11:159 – 70.
101
[26] Layne JN. Ontogeny. In: King JA, editor. Biology of Peromyscus (Rodentia). The American Society of Mammalogists. p. 148 – 253. [27] Lordi B, Patin V, Protais P, Mellier D, Caston J. Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring. Int J Psychophysiol 2000;37:195 – 205. [28] Margulis SW. Relationships among parental inbreeding, parental behavior and offspring viability in oldfield mice. Anim Behav 1998;55:427 – 38. [29] McCarthy MM, Bare J, Vom Saal FS. Infanticide and parental behavior in wild female house mice: effects of ovariectomy, adrenalectomy and administration of oxytocin and prostaglandin F2alpha. Physiol Behav 1986;36:17 – 23. [30] Millar JS. Tactics of energy partitioning in breeding in Peromyscus. Can J Zool 1975;53:967 – 76. [31] Nunes S, Fite JE, Patera KJ, French JA. Interactions among paternal behavior, steroid hormones, and paternal experience in male marmosets (Callithrix kuhli). Horm Behav 2001;39:70 – 82. [32] Patin V, Lordi B, Vincent A, Thomas JL, Vaudry H, Caston J. Effects of prenatal stress on maternal behavior in the rat. Dev Brain Res 2002;139:1 – 8. [33] Pepe GJ, Albrecht ED. Actions of placental and fetal adrenal steroid hormones in primate pregnancy. Endocr Rev 1995;16:608 – 48. [34] Petersson M, Hulting AL, Uvnas MK. Oxytocin causes a sustained decrease in plasma levels of corticosterone in rats. Neurosci Lett 1999;264:41 – 4. [35] Poley W. Emotionality related to maternal cannibalism in BALB and C57BL mice. Anim Learn Behav 1974;2:241 – 4. [36] Rave EH, Holler NR. Population dynamics of beach mice (Peromyscus polionotus ammobates) in southern Alabama. J Mammal 1992;73:347 – 55. [37] Reburn CJ, Wynne-Edwards KE. Hormonal changes in males of a naturally biparental and a uniparental mammal. Horm Behav 1999;35:163 – 76. [38] Rugh R. The mouse. Its reproduction and development. Oxford’ Oxford University Press; 1990. [39] Smith MH. The evolutionary significance of certain behavioral, physiological and morphological adaptations of the old-field mouse, Peromyscus polionotus. Ph.D. thesis, University of Florida. 1966. [40] Stebbins LL. Energy requirements during reproduction of Peromyscus maniculatus. Can J Zool 1977;55:1701 – 4. [41] Stern JM, Goldman L, Levine S. Pituitary – adrenal responsiveness during lactation in rats. Neuroendocrinology 1973;12:179 – 91. [42] Stocco DM. The role of the StAR protein in steroidogenesis: challenges for the future. J Endocrinol 2000;164:247 – 53. [43] Storey AE, Walsh CJ, Quinton RL, Wynne-Edwards KE. Hormonal correlates of paternal responsiveness in new and expectant fathers. Evol Hum Behav 2000;21:79 – 95. [44] Svare BB, Broida J, Kinsley C, Mann M. Psychobiological determinants underlying infanticide in mice. In: Hausfater G, Hrdy S, editors. Infanticide. New York’ Aldine Publishing Company; 1984. p. 387 – 400. [45] Svihla A. A comparative life history study of the mice of the genus Peromyscus. University of Michigan Museum of Zoology. Misc Publ 1932;24:1 – 39. [46] Uvnas MK. Oxytocin linked antistress effects: the relaxation and growth response. Acta Physiol Scand 1997;161(Suppl. 640):38 – 42. [47] Van Dijk JP, Challis JRG. Control and ontogeny of hypothalamic – pituitary – adrenal function in the fetal rat. J Dev Physiol 1989;12: 1 – 9. [48] Venihaki M, Carrigan A, Dikkes P, Majzoub JA. Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. Proc Nat Acad Sci U S A 2000; 97:7336 – 41. [49] Waddell BJ, Atkinson HC. Production rate, metabolic clearance rate and uterine extraction of corticosterone during the rat pregnancy. J Endocrinol 1994;143:183 – 90.
102
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
[50] Wasser SK, Hunt KE, Brown JL, Cooper K, Crockett CS, Bechert U, et al. A generalized fecal glucocorticoid assay for use in a diverse array of nondomestic mammalian and avian species. Gen Comp Endocrinol 2000;120:260 – 75. [51] Welsh TH, Kemper-Green CN, Livingston KN. Stress and reproduction. Encyclopedia of reproduction, vol. 4. Academic Press; 1999. p. 662 – 74. [52] Whitten PL, Brockman DK, Stavisky RC. Recent advances in noninvasive techniques to monitor hormone – behavior interactions. Yearb Phys Anthropol 1998;41:1 – 23. [53] Windle RJ, Shanks N, Lightman SL, Ingram CD. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 1997;138:2829 – 34.
[54] Wynne-Edwards KE, Reburn CJ. Behavioral endocrinology of mammalian fatherhood. Trends Ecol Evol 2000;15:464 – 8. [55] Ziegler TE. Hormones associated with non-maternal infant care: a review of mammalian and avian studies. Folia Primatol 2000;71: 6 – 21. [56] Ziegler TE, Washabaugh K.F, Snowdon CT. Responsiveness of expectant male cotton-top tamarins, Saguinus oedipus, to mate’s pregnancy. Horm Behav 2004;45:84 – 92.
Corticosteroids as potential mechanism regulating variability in reproductive success in monogamous oldfield mice (Peromyscus polionotus) Tatjana C. Good *, Kendra K. Harris, Chioma A. Ihunnah Department of Ecology and Evolutionary Biology, Princeton University, USA Received 26 May 2005; accepted 24 June 2005
Abstract Male and female mammals undergo profound hormonal changes during pregnancy, some of which are sufficiently dramatic to influence offspring survival. In order to understand the proximate mechanisms regulating the variability in reproductive success within and between individuals, we monitored changes in fecal corticosteroid concentrations over the reproductive cycle in male and female oldfield mice (Peromyscus polionotus subgriseus) to test whether corticosteroid concentrations during pregnancy were associated with offspring survival. In females that successfully raised litters to weaning, fecal corticosteroid concentrations were low until mid-gestation and increased significantly towards term; in females that did not raise their pups to weaning, fecal corticosteroid concentrations were significantly higher at mid-gestation, and remained high until late gestation. The difference in fecal corticosteroid concentrations at mid-gestation between successful and unsuccessful females can be explained by the fact that successful females were lactating. Lactation has been associated with a down-regulation of the hypothalamic – pituitary – adrenal (HPA) axis and, accordingly, a decrease in plasma corticosterone (CORT) in several species, including humans. Males that successfully raised their litters had low fecal corticosteroid concentrations throughout their partner’s pregnancy. Unsuccessful males, however, had significantly higher fecal corticosteroid concentrations at term than males that raised their pups to weaning. While these preliminary data require further investigation, we suggest that pre-partum fecal corticosteroid concentrations in males were responsible for the variability in reproductive success. D 2005 Elsevier Inc. All rights reserved. Keywords: Cannibalism; Fecal corticosteroids; Gestation; Hypothalamic – pituitary – adrenal axis (HPA); Infanticide; Paternal behavior; Pregnancy; Offspring survival; Oxytocin (OT)
1. Introduction Natural changes in the hypothalamic –pituitary – adrenal (HPA) axis in female mammals during pregnancy are well documented [9,25,51] and increases in corticosterone (CORT) near term are essential for the normal development of the fetus [18,33]. During rodent pregnancies, CORT
* Corresponding author. Centro de Ecologı´a Instituto Venezolano de Investigaciones Cientı´ficas, Apdo. 21827, Caracas 1020-A, Venezuela. Tel.: +58 212 504 1886; fax: +58 212 504 1197. E-mail address: [email protected] (T.C. Good). 0031-9384/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2005.06.030
concentrations typically increase from mid-gestation onwards, then drop dramatically at term [2,15,17,49]. The increase in maternal plasma CORT concentrations is most likely triggered by increasing metabolic demands of the pregnancy [22]. This increase in CORT secretion towards the end of pregnancy has several different functions: (1) it is essential for the maturation of several organs in the fetus, especially the lung and gut [18,33], (2) it plays a role in the onset of parturition (reviewed in Ref [25]) and (3) it is critical for the initiation and maintenance of lactation [10,41] at the end of pregnancy. However, the HPA axis can also exert multiple inhibitory effects on the female reproductive system when activated by
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
excessive stressors [51]. Glucocorticoids secreted from the adrenal cortex act at the levels of the hypothalamic, pituitary and gonadal tissues to suppress the gonadal axis [9], which can lead to adverse effects on reproductive functions (ovarian cyclicity, embryo development, neonatal weight, litter size, etc. [23]). Prenatal stress studies have demonstrated that high concentrations of CORT at specific times of the pregnancy can also have detrimental effects on the offspring (e.g. growth rates and memory: [27]). Glucocorticoids can also affect changes in parenting behaviors: stress during pregnancy has been demonstrated to decrease nurturing/nesting behaviors and pup retrieval in Swiss Webster mice [32]. Changes in corticosteroid concentrations may even play a role in mediating infanticidal and/or cannibalistic behavior [35]. With the recent development of non-invasive endocrine techniques such as the measurement of fecal steroids [19,50,52], it is now possible to monitor corticosteroid concentrations over the reproductive cycle of females without introducing artificial stress into the sampling procedure. In this study, we monitored fecal corticosteroid concentrations in male and female oldfield mice (Peromyscus polionotus subgriseus) over the female’s reproductive cycle to examine whether fecal corticosteroid concentrations could be regulating variability in reproductive success in these mice. Oldfield mice are socially and reproductively monogamous, mate for life and raise several litters together [14]. Furthermore, males and females exhibit extensive parental care in captivity [28,39]. Studies of naturally paternal species have demonstrated that hormones play a role in the onset and maintenance of male parental behavior [reviewed in Refs. [54] and [55]]. Particularly in species that form monogamous pair bonds, endocrinological changes in the male occur when cohabitating with the female [4,5,20,21,43]. However, the relationship between glucocorticosteroids and paternal care is not yet clear. Changes in cortisol concentrations before and after the birth of a litter did not differ between the biparental Djungarian hamster (P. campbelli) and the uniparental Siberian dwarf hamster (P. sungorus, [37]). In cotton-top tamarins (Saguinus oedipus), males showed an increase in urinary glucocorticosteroid concentrations possibly in response to the midpregnancy rise in glucocorticoids in females. This signal could potentially activate other hormonal changes in males to prepare them for their parenting role [56]. In men, cortisol concentrations also increased before births [43]. Elevated cortisol in men during late pregnancy and labor may help new fathers become attached to their newborns, as was shown for new mothers [13]. We hypothesized that fecal corticosteroid concentrations during the oldfield mouse pregnancy would differ between pairs that successfully raised all their litters to weaning and those pairs that never managed to raise pups. Based on the well-known temporal pattern of CORT during pregnancy in rodents, we predicted that successful females would
97
have lower corticosteroid concentrations than unsuccessful females until late gestation. Furthermore, we predicted that successful males would have higher corticosteroid concentrations than unsuccessful males during the latter half of their partners’ pregnancy in preparation for their parenting role.
2. Methods 2.1. Animals A total of 10 pairs of mice were used for this study. Pairs were housed together for 120 days, which corresponds to the average adult life expectancy in the field [36]. Animal care is explained in detail in Ref. [19]. All pups were raised with both parents and weaned by the experimenter at 20 days of age. ‘‘Successful’’ pairs (n = 4) were pairs that successfully raised four consecutive litters to weaning (20 days of age). ‘‘Unsuccessful’’ pairs never managed to raise pups to weaning (n = 4). Two pairs failed to raise their first litter, but eventually managed to raise the subsequent three litters (‘‘mixed-success’’ pairs). Births usually occur during the early daylight hours [26]. Pups were counted on the day of birth. Litters of unsuccessful pairs were all cannibalized within 24 h of birth. The parent responsible for the infanticide and/or cannibalism was unknown. 2.2. Fecal sample collection In order to minimize disturbance of the pair during the female’s pregnancy, we collected fecal samples rather than blood samples to monitor changes in corticosteroid concentrations in males and females through time. To avoid triggering any human-related cannibalism, sample collection began the day after the birth of the second litter and was never carried out on the day of birth of any litter. For 8 of 10 pairs, samples were collected during two consecutive gestation periods, beginning the day after the birth of the second litter until the birth of the fourth litter. For these pair, daily corticosteroid concentrations were averaged across the two gestation periods. For two pairs (one reproductively successful and one mixed-success pair), a complete set of fecal samples were available for the third gestation period only. Samples were collected daily between 8 and 10 am to avoid diel variations in corticosteroid concentrations [19]. Fecal samples were collected by holding the mice briefly in one hand and catching the pellets in a micro-centrifuge tube as they fell while avoiding urine contamination. Fecal samples were then stored in micro-centrifuge tubes at 20 -C until extraction. All animals were used to being handled daily since they were weaned. Therefore, we believe that the effect of restraint stress on corticosteroid concentrations during this study is negligible.
98
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
2.3. Fecal corticosteroid analysis
3. Results
All samples were assayed in duplicate at one-half volume by using a double-anti-body 125I-radioimmunoassay kit (ICN Pharmaceuticals, Costa Mesa, Calif.; catalog no. 07120102 for corticosterone) and counted on a Hewlett Packard Cobra II Auto Gamma Counter. Fecal samples were diluted 1:5 in the assay buffer prior to radioimmunoassay. Detailed information on fecal extraction and assay procedures are given elsewhere [19]. Intra- and inter-assay coefficient of variation was 7.4% and 18.5% for the low concentration fecal pool, and 7.6% and 14.0% for the high concentration fecal pool (n = 26). We ascertained that there was equal representation of different individuals and time points across assays. Corticosteroid concentrations are expressed as nanograms of hormone per gram of fecal matter.
3.1. Latency to birth of first litter, gestation period and number of pups born
2.4. Data analysis
3.2. Changes in corticosteroid concentrations in females
The gestation period was divided into three distinct time periods that reflect changes in circulating maternal CORT concentrations in the mouse: early gestation: days 1 – 10 (little CORT production by mother), mid-gestation: days 11– 15 (increased CORT production by mother) and late gestation: days 16– 19 (substantial CORT production by fetuses [2]). Due to their postpartum estrus, females conceive the day they give birth. Therefore, interbirth interval is equal to gestation period in this species. In oldfield mice, the mean gestation period is 23.8 days for non-lactating females and 28 days for lactating females [26]. Furthermore, the variability in gestation period is larger in the lactating females than in non-lactating females (see [45]) and is probably due to the competing energetic demands on the mother by the developing fetuses and nursing pups. To calculate the ‘‘trimester’’ lengths for females with different gestation periods, we divided each gestation period in proportion to the ‘‘trimester’’ lengths for a 19 day mouse gestation described above. All data were analyzed using the SPSS for Windows statistical package (Version 10.0.5). Differences in latency to birth of first litter, gestation period, number of pups born, and corticosteroid concentrations between successful and unsuccessful individuals were compared with Mann – Whitney U test. Due to the non-normality of errors introduced by limited sample sizes, we were unable to use a mixed between – within ANOVA to statistically evaluate the differences between successful and unsuccessful individuals across the three time periods. Unfortunately, there is no non-parametric equivalent to this test. Rather, changes in the temporal pattern of corticosteroid concentration across those three time periods were tested using the non-parametric equivalent of one-way repeated measures ANOVA (Friedman test). Tukey HSD post-hoc tests were conducted to determine differences between time periods within groups. P-values of less than 0.05 were considered significant.
Corticosteroid concentrations of the second and third successful pregnancies of the mixed-success females followed the same temporal pattern as those of successful females and were therefore pooled with the successful females for further analyses.
Successful pairs did not differ from unsuccessful pairs in latency to birth of first litter (Fig. 1A; U = 7.5; p = 0.89). However, raising a litter successfully to weaning affected the length of the gestation period of the next litter. The average gestation period of females that successfully raised their pups to weaning was significantly longer that that of females that did not raise their litters to weaning (Fig. 1B; U = 0; p = 0.03). The number of pups born in litters 1– 4 did not differ between successful and unsuccessful pairs (Fig. 2; U = 7.0; p = 0.89).
A
Latency to birth of first litter
35 30 25 20 15 10 5 0
B
successful
35
*
30
Gestation period
unsuccessful
25 20 15 10 5 0
successful
unsuccessful
Fig. 1. (A) Latency (+STDEV) to birth of first litter and (B) gestation period (+STDEV) for litters 2 – 4 in successful (n = 4) and unsuccessful (n = 4) pairs. *p < 0.05.
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102 6
difference between successful and unsuccessful females with respect to latency to birth of first litter or number of pups born. This suggests that there is no inherent difference in the ability of females to conceive or maintain a pregnancy. Successful (i.e. lactating) females had a longer gestation period than unsuccessful (i.e. non-lactating) females, which stands in agreement with Layne [26].
5 4 3 2
4.1. Changes in corticosteroid concentrations during pregnancy in the females
0
successful
unsuccessful
Fig. 2. Number of pups (+STDEV) born across all litters in successful (n = 4) and unsuccessful (n = 4) pairs.
There was a significant change in fecal corticosteroid concentrations across the three time periods for both successful (Friedman’s test: F (2, 23) = 5.01, p = 0.016) and unsuccessful (Friedman’s test: F (2, 20) = 11.31, p = 0.001) females. However, the increase in corticosteroid concentrations occurred at different times: There was a significant increase between mid- and late gestation (Tukey HSD test: p = 0.016) in successful females, whereas the significant increase in corticosteroid concentrations in unsuccessful females occurred between early and mid-gestation (Tukey HSD test: p = 0.009). Fecal corticosteroid concentrations did not differ significantly between successful and unsuccessful females at early (Fig. 3A; U = 78.0; p = 0.76) or late gestation (U = 11.0; p = 0.91). Fecal corticosteroid concentrations of unsuccessful females were significantly higher than those of successful and mixed-success females combined at midgestation (Fig. 3A; U = 1.0; p = 0.001). 3.3. Changes in corticosteroid concentrations in males There was no significant change in fecal corticosteroid concentration across the three time periods in successful (Friedman’s test: F (2, 23) = 2.39; p = 0.1) or in unsuccessful males (Friedman’s test: F (2, 20) = 0.56; p = 0.6). Fecal corticosteroid concentrations did not differ significantly between successful and unsuccessful males at early (Fig. 3B; U = 59.0; p = 0.32) or mid-gestation (U = 28.0; p = 0.88). However, fecal corticosteroid concentrations in unsuccessful males were significantly higher than in successful males at late gestation (Fig. 3B; U = 0; p = 0.01).
4. Discussion In this study, we monitored changes in fecal corticosteroid concentrations over the reproductive cycle in male and female oldfield mice (Peromyscus polionotus) to test whether corticosteroid concentrations during pregnancy were associated with offspring survival. There was no
In our study, successful and unsuccessful females did not differ in their corticosteroid concentrations in early gestation. Studies on rodent fetal organogenesis [38,47] and on the expression of genes responsible for the production of
A 140
Corticosteroid concentrations [ng/g]
1
120
successful females (n=6) unsuccessful females (n=4)
*
100 80 60 40 20 0 early
mid
late
Gestation
B 140
Corticosteroid concentrations [ng/g]
Number of pups born
99
120
successful males (n=6) unsuccessful males (n=4)
*
100 80 60 40 20 0 early
mid
late
Gestation Fig. 3. Fecal corticosteroid concentrations (+STDEV) throughout gestation in (A) females and (B) males. Note that corticosteroid concentrations for individuals with two gestation periods were averaged for each of the three time periods. *p < 0.05. (A) Successful (dark bars, n = 6) and unsuccessful (light bars, n = 4) females. Note that mixed-success females were added to the reproductively successful females for these analyses. (B) Successful (dark bars, n = 6) and unsuccessful (light bars, n = 4) males. Note that mixed-success males were added to the reproductively successful males for these analyses. High corticosteroid concentrations at term were associated with the loss of the litter immediately after parturition.
100
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
hormones along the HPA axis in the fetus [3,6,24,42,48] have demonstrated that circulating plasma CORT in early gestation is solely of maternal origin. Since early lactation is not yet energetically demanding [30,40], we did not expect differences in corticosteroid concentrations between successful and unsuccessful females at this time. Studies investigating adrenalectomy at various stages of the pregnancy [2,7] have demonstrated that the fetus produces much of the circulating CORT near term. In fact, the human fetus is responsible for at least two thirds of maternal plasma CORT concentrations at term [11]. The lack of significant difference in corticosteroid concentrations between successful and unsuccessful females at term can be explained by the fact that the majority of circulating maternal plasma CORT at this time is produced by the pups and that successful and unsuccessful females did not differ in the number of pups born. At mid-gestation, circulating CORT in mice is of maternal origin [2]. In our study, unsuccessful females had significantly higher corticosteroid concentrations at midgestation than successful females. Successful and unsuccessful females differed in one physiological condition: lactation. Successful females were simultaneously pregnant and lactating, whereas unsuccessful females were never lactating. During lactation, the HPA axis is down-regulated in several species, including humans [1,53], which could explain why corticosteroid concentrations in successful females were significantly lower than those of unsuccessful females. The HPA axis could be inhibited by oxytocin (OT), the hormone responsible for the stimulation of milk ejection during lactation [8,34,46].
previously presumed in mediating infanticidal behavior. However, there are alternative explanations for the observed patterns of increased corticosteroid concentration in the unsuccessful males at term: (1) corticosterone could indicate some other quality of the pairs, such as the ability to form pair bonds [37,43,56], and may only be indirectly related to infanticide; (2) changes in corticosterone concentrations in the males could trigger the release of other hormones, that in turn trigger infanticide. Detailed observation of parental behavior during gestation as well as during the first 24 h after parturition, and the monitoring of additional hormones such as prolactin [20], estrogen [12] or testosterone [31] throughout the female’s pregnancy in males and females would be necessary to determine the relationship between hormonal changes, parental behaviors and the resulting consequences for offspring survival.
4.2. Changes in corticosteroid concentrations during pregnancy in the males
Acknowledgments
In males of biparental mammalian species, paternal behavior is associated with changes in hormone concentrations over the reproductive cycle [54,55]. In oldfield mice, successful and unsuccessful males did not differ in corticosteroid concentrations until late gestation. Rather than triggering the onset of other hormonal changes in males to prepare them for their role in parenting, such as was found in male cotton-top tamarins [56] and men [43], high corticosteroid concentrations at term were associated with the loss of the litter. While most of the literature on the proximate mechanisms for the expression and inhibition of infanticide has focused on androgens, testosterone in particular [16,44], little research has been done on the effects of the HPA axis on infanticidal behavior. Available results are conflicting: while McCarthy et al. [29] reported that infanticidal behavior was not influenced by adrenalectomy in sexually inexperienced, adult female mice, Poley [35] demonstrated that cannibalistic females were more prone to auditory stress than non-cannibalistic ones. We hypothesize that corticosteroid concentrations may indeed play a bigger role than
4.3. Concluding remarks We were able to confirm the well-known patterns of corticosterone in females during lactation despite the limitations of small sample size and the choice of statistical analyses in this study. Therefore, we believe that the detected patterns of corticosteroid concentrations in males reflect true changes in the males’ physiology. These results therefore suggest a potential role of the HPA axis in infanticidal behavior. Clearly, this raises myriad new hypotheses, which should stimulate further research in this area.
Jeanne Altmann, Michaela Hau, Henry Horn, Memuna Khan, Lynn Martin, Martin Wikelski and three anonymous reviewers provided excellent comments on the manuscript. Ariana Renick assisted in many aspects of the lab work. Support was provided by the Princeton University, the Animal Behavior Society and the Society for Integrative and Comparative Biology to TCG and by a Mellon Summer Research Fellowship to KKH and CAI.
References [1] Amico JA, Johnston JM, Vagnucci AH. Suckling-induced attenuation of plasma cortisol concentrations in postpartum lactating women. Endocr Rev 1994;20:79 – 87. [2] Barlow SM, Morrison PJ, Sullivan FM. Plasma corticosterone levels during pregnancy in the mouse: the relative contributions of the adrenal glands and foeto – placental units. J Endocrinol 1974; 60:473 – 83. [3] Boudouresque F, Guillaume V, Grino M, Strbak V, Chautard T, ConteDevolx B, et al. Maturation of the pituitary – adrenal function in rat fetuses. Neuroendocrinology 1988;48:417 – 22. [4] Brown RE, Moger WH. Hormonal correlates of parental behavior in male rats. Horm Behav 1983;17:356 – 65.
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102 [5] Brown RE, Murdoch T, Murphy PR, Moger WH. Hormonal responses of male gerbils to stimuli from their mate and pups. Horm Behav 1995;29:474 – 91. [6] Bugnon C, Fellmann D, Gouget A, Cardot J. Ontogeny of the corticoliberin neuroglandular system in the rat brain. Nature 1982;298: 159 – 61. [7] Chatelain A, Dupouy JP, Allaume P. Fetal – maternal adrenocorticotropin and corticosterone relationships in the rat: effects of maternal adrenalectomy. Endocrinology 1980;106:1297 – 303. [8] Chiodera P, Salvarani C, Bacchi MA, Spallanzani R, Cigarini C, Gardini E, et al. Relationship between plasma profiles of oxytocin and adrenocorticotropin hormone during suckling or breast stimulation in women. Horm Res 1991;35:119 – 23. [9] Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic – pituitary – adrenal axis and the female reproductive system: clinical implication. Ann Intern Med 1998;129:229 – 40. [10] De Greef WJ, Van der Schoot P. Effect of adrenalectomy on the regulation of ovarian function during lactation. J Endocrinol 1983; 98:233 – 40. [11] Fencl MD, Stillman RJ, Cohen J, Tulchinsky D. Direct evidence of sudden rise in fetal corticoids late in human gestation. Nature 1980; 287:225 – 6. [12] Fite JE, French JA. Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is there a link with infant survivorship and maternal behavior? Horm Behav 2000;38:1 – 12. [13] Fleming AS, Ruble D, Krieger H, Wong PY. Hormonal and experiential correlates of maternal responsiveness during pregnancy and the puerperium in human mothers. Horm Behav 1997;31: 145 – 58. [14] Foltz DW. Genetic evidence for long-term monogamy in a small rodent, Peromyscus polionotus. Am Nat 1981;117:665 – 75. [15] Gala RR, Westphal U. Corticosteroid-binding activity in serum of mouse, rabbit and guinea pig during pregnancy and lactation: possible involvement in the initiation of lactation. Acta Endocrinol 1967;55: 47 – 61. [16] Gandelman R. Hormones and infanticide. In: Svare BB, editor. Hormones and aggressive behavior. New York’ Plenum Press; 1983. p. 105 – 18. [17] Garland HO, Atherton JC, Baylis C, Moran MRA, Milne CM. Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies. J Endocrinol 1987;113:435 – 44. [18] Gartner H, Graul MC, Oesterreicher TJ, Finegold MJ, Henning SJ. Development of the fetal intestine in mice lacking the glucocorticoid receptor (GR). J Cell Physiol 2002;194:80 – 7. [19] Good T, Khan MZ, Lynch JW. Biochemical and physiological validation of a corticosteroid radioimmunoassay for plasma and fecal samples in oldfield mice (Peromyscus polionotus). Physiol Behav 2003;80:405 – 11. [20] Gubernick DJ, Nelson RJ. Prolactin and paternal behavior in the biparental California mouse, Peromyscus californicus. Horm Behav 1989;23:203 – 10. [21] Gubernick DJ, Winslow JT, Jensen P, Jeanotte L, Bowen J. Oxytocin changes in males over the reproductive cycle in the monogamous, biparental California mouse Peromyscus californicus. Horm Behav 1995;29:59 – 73. [22] Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia’ W.B. Saunders Company; 2000. [23] Herrenkohl LR. Prenatal stress reduces fertility and fecundity in female offspring. Science 1979;206:1097 – 9. [24] Keegan CE, Herman JP, Karolyi J, O’Shea KS, Camper SA, Seasholtz AF. Differential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain. Endocrinology 1994;134: 2547 – 55. [25] Keller-Wood ME, Wood CE. Pituitary – adrenal physiology during pregnancy. Endocrinologist 2001;11:159 – 70.
101
[26] Layne JN. Ontogeny. In: King JA, editor. Biology of Peromyscus (Rodentia). The American Society of Mammalogists. p. 148 – 253. [27] Lordi B, Patin V, Protais P, Mellier D, Caston J. Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring. Int J Psychophysiol 2000;37:195 – 205. [28] Margulis SW. Relationships among parental inbreeding, parental behavior and offspring viability in oldfield mice. Anim Behav 1998;55:427 – 38. [29] McCarthy MM, Bare J, Vom Saal FS. Infanticide and parental behavior in wild female house mice: effects of ovariectomy, adrenalectomy and administration of oxytocin and prostaglandin F2alpha. Physiol Behav 1986;36:17 – 23. [30] Millar JS. Tactics of energy partitioning in breeding in Peromyscus. Can J Zool 1975;53:967 – 76. [31] Nunes S, Fite JE, Patera KJ, French JA. Interactions among paternal behavior, steroid hormones, and paternal experience in male marmosets (Callithrix kuhli). Horm Behav 2001;39:70 – 82. [32] Patin V, Lordi B, Vincent A, Thomas JL, Vaudry H, Caston J. Effects of prenatal stress on maternal behavior in the rat. Dev Brain Res 2002;139:1 – 8. [33] Pepe GJ, Albrecht ED. Actions of placental and fetal adrenal steroid hormones in primate pregnancy. Endocr Rev 1995;16:608 – 48. [34] Petersson M, Hulting AL, Uvnas MK. Oxytocin causes a sustained decrease in plasma levels of corticosterone in rats. Neurosci Lett 1999;264:41 – 4. [35] Poley W. Emotionality related to maternal cannibalism in BALB and C57BL mice. Anim Learn Behav 1974;2:241 – 4. [36] Rave EH, Holler NR. Population dynamics of beach mice (Peromyscus polionotus ammobates) in southern Alabama. J Mammal 1992;73:347 – 55. [37] Reburn CJ, Wynne-Edwards KE. Hormonal changes in males of a naturally biparental and a uniparental mammal. Horm Behav 1999;35:163 – 76. [38] Rugh R. The mouse. Its reproduction and development. Oxford’ Oxford University Press; 1990. [39] Smith MH. The evolutionary significance of certain behavioral, physiological and morphological adaptations of the old-field mouse, Peromyscus polionotus. Ph.D. thesis, University of Florida. 1966. [40] Stebbins LL. Energy requirements during reproduction of Peromyscus maniculatus. Can J Zool 1977;55:1701 – 4. [41] Stern JM, Goldman L, Levine S. Pituitary – adrenal responsiveness during lactation in rats. Neuroendocrinology 1973;12:179 – 91. [42] Stocco DM. The role of the StAR protein in steroidogenesis: challenges for the future. J Endocrinol 2000;164:247 – 53. [43] Storey AE, Walsh CJ, Quinton RL, Wynne-Edwards KE. Hormonal correlates of paternal responsiveness in new and expectant fathers. Evol Hum Behav 2000;21:79 – 95. [44] Svare BB, Broida J, Kinsley C, Mann M. Psychobiological determinants underlying infanticide in mice. In: Hausfater G, Hrdy S, editors. Infanticide. New York’ Aldine Publishing Company; 1984. p. 387 – 400. [45] Svihla A. A comparative life history study of the mice of the genus Peromyscus. University of Michigan Museum of Zoology. Misc Publ 1932;24:1 – 39. [46] Uvnas MK. Oxytocin linked antistress effects: the relaxation and growth response. Acta Physiol Scand 1997;161(Suppl. 640):38 – 42. [47] Van Dijk JP, Challis JRG. Control and ontogeny of hypothalamic – pituitary – adrenal function in the fetal rat. J Dev Physiol 1989;12: 1 – 9. [48] Venihaki M, Carrigan A, Dikkes P, Majzoub JA. Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. Proc Nat Acad Sci U S A 2000; 97:7336 – 41. [49] Waddell BJ, Atkinson HC. Production rate, metabolic clearance rate and uterine extraction of corticosterone during the rat pregnancy. J Endocrinol 1994;143:183 – 90.
102
T.C. Good et al. / Physiology & Behavior 86 (2005) 96 – 102
[50] Wasser SK, Hunt KE, Brown JL, Cooper K, Crockett CS, Bechert U, et al. A generalized fecal glucocorticoid assay for use in a diverse array of nondomestic mammalian and avian species. Gen Comp Endocrinol 2000;120:260 – 75. [51] Welsh TH, Kemper-Green CN, Livingston KN. Stress and reproduction. Encyclopedia of reproduction, vol. 4. Academic Press; 1999. p. 662 – 74. [52] Whitten PL, Brockman DK, Stavisky RC. Recent advances in noninvasive techniques to monitor hormone – behavior interactions. Yearb Phys Anthropol 1998;41:1 – 23. [53] Windle RJ, Shanks N, Lightman SL, Ingram CD. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 1997;138:2829 – 34.
[54] Wynne-Edwards KE, Reburn CJ. Behavioral endocrinology of mammalian fatherhood. Trends Ecol Evol 2000;15:464 – 8. [55] Ziegler TE. Hormones associated with non-maternal infant care: a review of mammalian and avian studies. Folia Primatol 2000;71: 6 – 21. [56] Ziegler TE, Washabaugh K.F, Snowdon CT. Responsiveness of expectant male cotton-top tamarins, Saguinus oedipus, to mate’s pregnancy. Horm Behav 2004;45:84 – 92.