Prostaglandin F2α and control of reproduction in female swine: A review

Available online at www.sciencedirect.com

Theriogenology 77 (2012) 1–11 www.theriojournal.com

Review

Prostaglandin F2␣ and control of reproduction in female swine: A review F. De Rensisa,*, R. Saleria, P. Tummarukb, M. Techakumphub, R.N. Kirkwoodc b

a Faculty of Veterinary Medicine, University of Parma, Italy Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand c School of Animal and Veterinary Sciences, University of Adelaide, Australia 5005

Received 6 April 2011; received in revised form 22 July 2011; accepted 25 July 2011

Abstract In female swine, PGF2␣ is an important regulator of corpora luteal (CL) function, uterine contractility, ovulation, and embryo attachment. High affinity PGF2␣ receptors are present in the CL at all stages of the estrous cycle and they are functional. Therefore, a lack of luteolytic capacity of PGF2␣ is related to other factors that have not been well identified. In female pigs, a single exogenous PGF2␣ injection produces a short lasting decrease in plasma progesterone levels but does not induce luteolysis before day 12 of the estrous cycle. However, multiple injections of PGF2␣ can induce luteolysis before day 12 of the estrous cycle and may be utilized in the development of protocols for ovulation synchronization and timed AI. Most commonly, PGF2␣ is used for the induction of farrowing and so facilitation of cross fostering. Further, since PGF2␣ is a smooth muscle stimulant, treatment to stimulate myometrial contractions and uterine evacuation of residual products from parturition or infectious debris, may have beneficial effects on post-weaning fertility. Administration of PGF2␣ at the moment of insemination has been shown to improve reproductive performances when fertility is otherwise low, such as in sow under summer heat stress. © 2012 Elsevier Inc. All rights reserved.

Contents 1. 2. 3.

Introduction ................................................................................................................................ Synthetic PGF2␣ .......................................................................................................................... PGF2␣ receptors .......................................................................................................................... 3.1. Presence and distribution of FPr ............................................................................................... 3.2. The effects of PGF2␣ administration on the CL ............................................................................ 3.3. Conclusion ......................................................................................................................... 4. PGF2␣ During the estrous cycle ....................................................................................................... 4.1. Pattern of PGF2␣ secretion ..................................................................................................... 4.2. Conclusion ......................................................................................................................... 5. PGF2␣ and pregnancy maintenance ................................................................................................... 6. PGF2␣ and induction of farrowing .................................................................................................... 7. PGF2␣ and periparturient behaviour in pregnant sows ............................................................................. 8. PGF2␣ treatment during early postpartum period ................................................................................... 9. PGF2␣ administration at insemination ................................................................................................ 10. Conclusion .................................................................................................................................

* Corresponding author: Tel.: 00390521902659; fax: 00390521902798. E-mail address: [email protected] F. (F. De Rensis) 0093-691X/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.theriogenology.2011.07.035

2 2 2 2 3 3 4 4 4 5 5 6 6 6 7

2

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

References ........................................................................................................................................

1. Introduction The purpose of this paper is to review the activities of PGF2␣ in female swine and discuss some practical applications in swine reproduction. In the 1960s it was demonstrated that uterine flushing collected from gilts in their late luteal phase had an in vitro luteolytic effect [1]. Thereafter, in vivo studies demonstrated that the endometrium of cycling gilts around day 15 of their estrous cycle contained a luteolytic substance, PGF2␣, and that the uterine endometrium was the most important source [2–5]. In sows, as in cows and ewes, the uterine PGF2␣ is secreted into the uterine vein and then moved by counter current transfer to the ovarian artery and then to the ipsilateral ovary and to the systemic circulation [6,7]. Many studies have demonstrated that PGF2␣ is an important regulator of CL function, uterine contractility, ovulation, and embryo attachment. Therefore, PGF2␣ administration becomes an important tool for control of swine reproduction. The goals of this paper are to describe in female swine the pattern of PGF2␣ secretion during different reproductive stages and the main applications of PGF2␣ administration in the control of reproduction. The first part of this review briefly describes the characteristics, distribution, and function of PGF2␣ receptors and some of the mechanisms by which PGF2␣ controls CL activity. 2. Synthetic PGF2␣ The first PGF2␣ product became available in 1979 (Lutalyse or Dinoprost) and, thereafter, several agonists and generic PGF2␣ products became available. The major difference in available products is that some are chemically the same as uterine-derived PGF2␣ [8] and others are chemically the same as its agonist, cloprostenol sodium [9]. Cloprostenol exists as two optically active isomers (D- and L-cloprostenol) and a racemic mixture, DL-cloprostenol [10]. Most commercial products contain the racemic mixture which is obtained by chemical synthesis [9]. Both DL-cloprostenol and the pure D-cloprostenol are used in veterinary medical products; however, only the D-isomer of cloprostenol binds to the PGF2␣ receptors in bovine CL and myometrial cells and exhibits luteolytic activity [11]. Dcloprostenol is approximately 10-fold more potent than

7

DL-cloprostenol [12], so when D-cloprostenol is used a lower dosage is effective. Compared to Dinoprost, cloprostenol has a greater affinity for PGF2␣ receptors [13] and a longer half life in the circulation, 3 h vs a few minutes [9], because in cloprostenol a benzyl chloride ring is substituted at position 17 of the fatty-acid structure of the PGF2␣. Whether this makes the agonist more effective in lysing CL is equivocal. Clearance of PGF2␣ is accomplished by one or two passages through the liver and lungs, and its residues do not accumulate in blood after repeated daily injection [8]. Side effects of PGF2␣ include a slight increase in frequency of defecation, respiratory rate, shivering, nervousness, and a general indication of discomfort such as restlessness, chewing, and grinding of teeth, which are likely responses to colic. The severity can vary between animals, but in most cases these side effects subside 1 to 2 h after treatment [14]. 3. PGF2␣ receptors The action of PGF2␣ appears to be primarily, if not exclusively, mediated by a plasma membrane receptor termed FP receptor (FPr). The structure of the FPr gene, regulation of luteal FPr mRNA, and receptor/ligand interaction requirements for the FPr protein have been reviewed previously [15]. Prostaglandin receptors are members of the seven-transmembrane domain receptor superfamily. It appears a single gene encodes for FPr, and FPr mRNA has been cloned from mice, rats, sheep, cows, humans, and pigs [15]. 3.1. Presence and distribution of FPr In pigs, PGF2␣ acts by a systemic and a local mechanism to induce luteolysis. Unilateral hysterectomy leads to regression of CL on both sides, indicating a systemic effect of uterine PGF2␣ [16]. However, if three fourths of the remaining horn is removed only CL on the ipsilateral side of the remaining uterine tissue regresses, indicating a local effect of PGF2␣ [17]. In either case, uterine PGF2␣ initiates luteolysis in pigs [18]. The specific high affinity PGF2␣ receptors are present in the CL at all stages of the estrous cycle and they are primarily located on large luteal cells [19]. FP receptors are already abundant in bovine, ewe, and swine CL by day 5 of the estrous cycle [19,20] but

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

while in bovine and ewe the FP receptors concentration do not change (i.e., in CL with or without luteolytic capacity) [21], in swine the concentrations of FP receptors increase near the time of acquisition of luteolytic capacity [19,20]. However, swine CL do have up to 2 ⫻ 106 FP receptors per large luteal cell prior to acquisition of luteolytic capacity and so a lack of luteolytic capacity of PGF␣ prior to day 12 in swine is not due to an absence of PGF2␣ receptors on luteal cells [19,20]. In the CL, the PGF2␣ binds to the G-protein-coupled FP receptors leading to an elevation of free intracellular calcium and activation of protein kinase C (PKC) [22,23]. The events occurring after PKC activation and elevation in calcium have been not fully described. However, in swine, activation of the FPr by PGF2␣ in a responsive CL initiates a cascade of intracellular events that results in luteolysis [19] with a dramatic change in regulation of several pathways by PGF2␣ such as intraluteal estradiol and progesterone production and signalling [24 –26] and, as has been described in the bovine, possibly the production of endothelin-1 (ET-1) and monocyte chemo-attractant protein-1 (MPC-1) [25,27]. Finally it has been observed that the acquisition of luteolytic capacity in the porcine CL involves PGF2␣ inhibiting cholesterol transport pathways (StAR, LDL receptor) through PGF2␣ regulation of LH receptors and DAX1 [28]. Cloprostenol treatment can induce PGF2␣ production from CL tissue cultured in vitro [29,30] suggesting that the small amount of uterine PGF2␣ that reaches the CL can initiate an auto-amplification pathway that causes intraluteal production of PGF2␣. However, PGF2␣ production is induced by cloprostenol only in CL with luteolytic capacity (d 17), not in those without luteolytic capacity (d 9) [24]. In conclusion, understanding the control of intraluteal PGF2␣ production may provide some understanding of the cellular and molecular basis for the luteolytic capacity of PGF2␣ in swine and may be useful in developing methods to promote luteolysis before day 12 of estrous cycle or to prevent luteal regression. 3.2. The effects of PGF2␣ administration on the CL In swine, treatment with PGF2␣ induces a number of changes in gene expression that are similar regardless of whether the CL has or has not acquired luteolytic capacity. However, the full luteolytic program is activated only after day 12 of the estrous cycle [24 – 27,31]. Differential gene expression in response to PGF2␣ is consistent with alterations in transcription factors. One key family of transcription factors known

3

to be expressed in the pig CL is that for steroid hormones [32,33]. Steroid binding to these receptors is known to regulate many physiological processes including both luteotrophic [34,35] and luteolytic [36 – 39] roles for estrogen and estrogen receptors (ER␣ and ER␤). In swine CL with luteolytic capacity there is increased luteal estradiol production due to a dramatic increases in aromatase expression [25]. This observation indicates a shift in steroid production and luteal steroid hormone receptors in the CL at the beginning of luteolysis and this mechanism is a key part of the complete program for regression of the CL. At the time of swine embryo attachment, estradiol implants promote CL function [34,40], demonstrating an anti-luteolytic effect of estradiol. Conversely, a luteolytic role for estradiol and ER␤ expression in gilts occurred during luteolysis [26]. It has been observed that PGF2␣ administration induce ER␤ mRNA and decrease ER␣ mRNA only on day 17 CL and not day 9 CL [26]. Therefore the different roles of estrogens in the CL could be explained by changes in estrogen receptors population dynamics [26]. There is evidence suggesting that ER␣ and ER␤ have different, even opposing, effects on cell function and that the ERs interact with other transcription factors to produce specific physiological actions [25,37,41– 44]. In pigs, luteal production of estradiol and luteal expression of steroid receptors can be regulated by PGF2␣ [26]. The failure to up-regulate these pathways in day 9 CL may be responsible, in part, for the inability of PGF2␣ to induce luteolysis at this time [26]. There are several other reasons given in the literature for the refractoriness of the early CL to the administration of a luteolytic dose of PGF2␣, including lack of expression of PGF2␣ receptors and the presence of the PGF2␣ catabolising enzyme, 15-hydroxyprostaglandin dehydrogenase (PGDH) [45,46]. In addition, changes in blood flow, alteration in gene expression (VEGF, eNOS, angioprotein, angiotensin, endothelin, CAMKK2, HINT1, YWHAZ, GNB1 and RGS2), and in NO and pO2, may also affect the luteolytic effects of PGF2␣ in a recently formed CL [47,48]. 3.3. Conclusion Several studies indicate that FPr in porcine CL are present before acquisition of luteolytic capacity and that they are functional. Therefore, the lack of luteolytic capacity of PGF2␣ prior to day 12 of the estrous cycle is related to other factors that have not been well identified. The activation of intracellular second messenger(s), the cholesterol transfer (STaR ar/and LDL re-

4

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

ceptors) mechanism and/or, as will be described later, the steroidogenic effects of progesterone and/or estradiol may be some of these factors. Differences between in vitro and in vivo data concerning the luteolytic capacity of PGF2␣ could be related to the fact that, in vivo, several extrinsic hypophyseal and uterine factors participate in the control of luteolytic effects obtained from systemic administration of PGF2␣. 4. PGF2␣ During the estrous cycle The estrous cycle is regulated by many hormones, including PGF2␣, which is known to have the ability to regress the CL and is routinely used for estrus synchronization in cattle [49 –52]. During spontaneous luteolysis in swine at day 15–16 of the estrous cycle, PGF2␣ causes a dramatic decrease in progesterone production and structural regression of CL [53,54]. 4.1. Pattern of PGF2␣ secretion The PGF2␣ plasma profile is usually described in terms of concentrations of PGF2␣ metabolite (PGFM). The PGF2␣ in the blood is quickly metabolized into a stable biologically inactive form by NAD-dependent 25-hydroxyprostaglandin dehydrogenase (15-PGDH) [55] and measuring PGFM in peripheral blood is an effective way of estimating uterine PGF2␣ secretion in pigs [56]. In domestic animals, luteal regression is caused by PGF2␣ secreted from the uterus [57–59] in a series of discrete pulses [55–58], although there are some species differences in PGF2␣ profiles. In cows, luteolysis has been observed to involve two distinct phases of uterine PGF2␣ secretion differing in pulse magnitude and occurring approximately every 12 h [60 – 63] whereas in ewes, there is a gradual increase in the magnitude of pulses [64]. In swine there are few data although it has been reported that uterine PGF2␣ pulses generally occur at 6 to 8 h intervals [65]. In pigs, the luteolytic efficacy of PGF2␣ administration during the estrous cycle has been investigated with the aim to develop a protocol for synchronization of estrus and ovulation. The first studies observed that the administration of 0.1 or 2.5 mg PGF2␣ into each uterine horn at day 10 of the estrous cycle was not able to decrease plasma progesterone levels [66]. These and other studies [14,54,67,68] concluded that a single PGF2␣ administration would induce luteolysis only after day 12 of the estrous cycle. These data are supported by in vitro data showing that treatment with PGF2␣ decreased in vitro progesterone production from day 12 (87%) but not day 9 CL [31]. In contrast,

multiple administrations of PGF2␣ have been observed to induce luteolysis sooner. In cows, variable luteolytic responses have been noted when a single dose of PGF2␣ has been given on day 5 of the estrous cycle, when CL have not yet a luteolytic capacity in this species, but when two doses of PGF2␣ were employed the refractoriness of the early CL was overcome [69 – 72]. Similarly in ewes, very low doses of PGF2␣ (40 – 200 mg/7h) can induce luteal regression in CL without luteolytic capacity if given in repeated treatments [64]. In gilts, administration of 25 mg dinoprost every 12 h from day 5 to day 10 of the estrous cycle can induce lueolysis in CL without luteolytic capacity [73,74] and four injections of synthetic PGF2␣ analogue administered every 12 h beginning on day 10 of the estrous cycle was more likely to induce luteolysis than a single injection [67]. Finally, in mini pigs two administration of cloprostenol at 3.0 mg/12 h can induce luteolysis beginning 7 days after ovulation [75]. Given the increased sensitivity to PGF2␣ as CL age beyond 12 days, an alternative approach for using PGF2␣ in a swine estrus control program is to breed to obtain pregnancy and then to abort the pregnancy at some time beyond day 12. Alternatively, pseudopregnancy could be induced by administration of exogenous estrogen to mimic the embryonic signal for maternal recognition of pregnancy and then PGF2␣ used to lyse CL after day 12 [76]. Interestingly, induced CL in very young pre-pubertal gilts have been shown to be more sensitive to prostaglandin-induced luteolysis than were the spontaneous corpora lutea of post-pubertal gilts at the second or third estrus [77]. Further the induction of accessory CL in normally cycling gilts, followed by PGF2␣, provided an effective estrus control protocol [67]. However, a more recent attempt was not successful and may point to a need for higher gonadotrophin doses to successfully induce accessory CL in cyclic gilts [78]. 4.2. Conclusion In swine, a single PGF2␣ administration will not induce complete luteolysis before day 12 of the estrous cycle. However, multiple injections have demonstrated some efficacy. Although speculative, it is possible that the use of longer–acting PGF2␣ analogues may induce luteolysis with a single or very few administrations and so facilitate its use for estrus synchronization in swine. An alternative approach is to allow CL maintenance beyond day 12 by inducing pregnancy or pseudopregnancy or inducing more sensitive accessory CL. If accessory CL were successfully induced, the subse-

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

quent administration of PGF2␣ would provide for effective estrus synchronization.

Table 1 Effect of dose and route of injection of Lutalyse on percent of sows farrowing in different time periods after injection. Time from Lutalyse injection to farrowing

5. PGF2␣ and pregnancy maintenance The establishment and maintenance of pregnancy is all about maintaining the function of the corpora lutea. At about day 14 in the non-pregnant female pig there are episodic releases of luteolytic PGF2␣. This PGF2␣ and the luteoprotective PGE2 are produced in the endometrium [79,80] with the proper ratio of PGE2 to PGF2␣ being responsible for successful maintenance of pregnancy in the pig [81]. Endometrial content of PGF2␣ changes significantly in pregnant sows, with the lowest levels on days 10 –11 followed by a 42-fold increase on day 12 and then remaining high throughout pregnancy [79,82]. In swine, the mechanism by which the embryo blocks the luteolytic effect of PGF2␣ is based on the blastocysts secreting estradiol which, in concert with prolactin, redirects the endometrial secretion of PGF2␣ into the uterine lumen rather than the uterine vein [83,84]. So, in contrast to ruminants, the luteolytic signal is produced by pregnant pigs but is prevented from reaching the ovarian target tissue. Interestingly, Ford et al [34] were unable to overcome the luteolytic effect of PGF2␣ with estradiol administered directly into CL. Although it would appear that the primary action of estrogen in the maternal recognition of pregnancy is anti-luteolytic at the level of uterus [85] (reducing PGF2␣ secretion into uterine vasculature), a direct anti-luteolytic action via decreased PGF2␣ receptor concentrations on luteal cells cannot be excluded. The latter observation is supported by the data showing of a reduction in PGF2␣ receptors on day 14 in pregnant and pseudopregnant compared to cycling pigs [20]. Therefore, a reduction of PGF2␣ receptor concentration is a mechanism that also may be involved in the maternal recognition of pregnancy in swine. 6. PGF2␣ and induction of farrowing Because of its luteolytic effect, PGF2␣ and analogues are widely used in sows for the induction of farrowing so that parturition can be synchronized and cross fostering facilitated if required. The mechanism of action of PGF2␣ in pregnancy termination is not fully understood and there are important differences between species. Goats and pigs require functional CL for their entire gestation while in other species the

5

10 mg IM 5 mg IM 5 mg vulva 2.5 mg vulva

8–24 h

24–32 h

32–48 h

⬎ 48 h

19 12 18 15

50 41 61 62

19 6 16 9

12 41 9 15

source of progesterone varies with stages of gestation [86 – 89]; e.g., mares are dependent upon luteal progesterone for the first 170 d of pregnancy and cows are dependent for about 200 d of pregnancy [90]. Administration of a luteolytic dose of PGF2␣ during the period of CL dependence results in luteolysis and, therefore, pregnancy should terminate. After the period of luteal dependence the source of progesterone is placental. In humans, PGF2␣ can terminate pregnancy during the placental progesterone phase by inducing uterine contractions [91]. It is widely accepted that induction of farrowing in sows can be successfully achieved by a single intramuscular (IM) injection of PGF2␣ or an analogue. Most studies show that more than 80% of sows will farrows within 36 h of an IM injection at the manufacturer’s label dose given at 112–114 d of gestation [92–99]. However, the lack of predictability within this 36 h constrains wider use. More recently, it was demonstrated that if injected into the vulva the effective dose can be reduced to 50% or even 25% of the IM dose ([100,101]; Table 1). This could be due to the fact that the lymphatic and venous vessels of the female reproductive tract are greatly interconnected, resulting in an increased local concentration of PGF2␣ and without first-pass effects in the lung [102,103]. The occasional failure of a single injection of PGF2␣ may be due to a non-terminal luteolysis; i.e., luteolysis is initiated, circulating progesterone concentrations fall, but then the CL recovers and pregnancy is maintained. This effect can be countered and a terminal luteolysis induced if PGF2␣ is administered twice with a 6 h interval (“split-dose”), the incidence of non-response being greatly reduced with most sows farrowing during the next working day ([101]; Table 2). Therefore, for optimal efficacy, we recommend that PGF2␣ be administered vulvally (externally at the vulva-cutaneous junction) as a split dose with each injection at 50% of the label dose.

6

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

Table 2 Effect of a single or repeated (“split-dose”) injection of cloprostenol on percent of sows farrowing in different time periods after injection. Time from cloprostenol injection to farrowing Single Split-dose

8–22 h

22–32 h

32–46 h

⬎ 46 h

17 10

56 84

14 2

5 0

treatment increased piglet weight at weaning and reduced neonatal mortality [125]. Some differences in the results could be due to the type of prostaglandin utilized (natural or cloprostenol) and to the experimental design. However, given the limited and unpredictable response of sows to post partum PGF2␣ treatment, its routine use is not recommended. 9. PGF2␣ administration at insemination

7. PGF2␣ and periparturient behaviour in pregnant sows PGF2␣ is involved in the control of sow behaviour during the peripartum period. Indeed, a single injection of PGF2␣ has been shown to stimulate nest building behaviour and a desire to leave the social group to select a nest site in prepartum and pseudopregnant gilts and sows [104 –108]. Gilbert et al [107] show that although PGF2␣ induced nest building behaviour, there were few subsequent effects on gilt/piglet interactions. 8. PGF2␣ treatment during early postpartum period Post-partum PGF2␣ has been used as a treatment to reduce the incidence of post-partum dysgalactia syndrome in sows [109]. One mechanism may be that incomplete luteolysis results in inappropriately high post-partum progesterone concentrations [110] which would inhibit sow milk production. However, the effect of PGF2␣ on the occurrence of postpartum dysgalactia syndrome is controversial since it is only effective in some herds [111]. It has been suggested that in the absence of clinical signs, such as vulval discharges, treatment with PGF2␣ will not improve either sow or litter performance [112]. Postpartum administration of PGF2␣ enhanced uterine involution and reduced the risk of postpartum endometritis [113]. Several studies have reported a fertility benefit of using PGF2␣ during the early postpartum in sows with or without reproductive problems [114 –121]. It has been observed that PGF2␣ facilitated uterine contractions and evacuation of uterine debris postpartum, reducing the incidence of endometritis and allowing sows to more fully express their milk yield potential and improving post-weaning fertility [122,123]. A reduction in the weaning-estrus interval and an increased number of pigs born alive in the subsequent litter have ben noted following PGF2␣ treatment [114,115,119, 120] but in one study this occurred only in 7th parity or older sows [124]. It was also observed that PGF2␣

The preovulatory LH surge stimulates increased intra-follicular PGF2␣ synthesis which, in turn, stimulates the activation of enzymes such as collagenase and elastase involved in follicular rupture [126]. The intrauterine infusion of estrogen has been shown to increase PGF2␣ in the uterine vein that is then transported by countercurrent transfer to the ovarian artery and ultimately into ovarian follicles [127]. Further, the administration of 500 ␮g of cloprostenol induced earlier ovulation in PMSG/hCG treated prepubertal gilts [128] and transcervical infusion of PGF2␣ led to an intra-follicular increase in PGF2␣ concentration and advanced ovulation by approximately 12 h [129]. These data indicate that exogenous PGF2␣ may advance the time of ovulation through an intra-follicular mechanism. The injection of PGF2␣ at the time of insemination, or its inclusion in semen doses, variably improved farrowing rate and litter size [130 –134]. However, differences related to the fertility of the farm at the time of the study are important. Indeed, the advantageous effect

Table 3 Effect of administration of cloprostenol or PGF2␣ at insemination on sow fertility.

Cloprostenol Control PGF2␣ Control PGF2␣* Control PGF2␣ Control PGF2␣* Control PGF2␣ Control PGF2␣† Control

Farrow, %

Litter size

Ref

83.8 90.0 83.9 80.9 78.5‡ 54.4 87.8‡ 80.6 69.4‡ 54.4 88.9‡ 67.4 89.9‡ 69.9

9.6 10.3 11.2‡ 10.0 10.8‡ 9.1 11.3‡ 10.0 10.8‡ 8.5 10.8‡ 9.6 10.7‡ 9.6

[131] [130] [130] [132] [132] [134] [133]

* Data from sows in summer † Data from sows returning to estrus following first service after weaning ‡ Mean significantly different from control

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

7

Fig. 1. Main effects of PGF2␣ administration in the control of swine reproduction.

of PGF2␣ is usually detected when fertility was otherwise low, such as due to the summer heat stress, and not during the rest of the year, or in sows returning to estrus after post weaning service (Table 3). Supplementation of semen doses with the prostaglandin analogue cloprostenol enhanced uterine contractions [135]. Therefore, although the mechanism involved was not determined, it is reasonable to assume that the effects of prostaglandin are mediated by an effect on sperm transport to the oviduct, although an effect on timing of ovulation cannot be completely ignored [127]. 10. Conclusion Figure 1 summarizes the main effects of PGF2␣ administration in the control of swine reproduction. Administration at one or two days before expected farrowing is an effective method for farrowing induction. Administration at insemination can increase pregnancy rate but likely only on farms with relatively low fertility, as may occur in heat stressed animals during the warm season of the year. Until about day 12 of the estrous cycle, porcine CL are insensitive to the lueolytic effects of PGF2␣ so these products are not useful for estrus synchronization protocols in pigs. However, this aspect requires fur-

ther investigation since luteolysis will occur sooner if serial injections are given. References [1] Schomberg DW. Demonstration in vitro of luteolytic activity in pig uterine flushing. J Endocrinol 1967;38:359 – 61. [2] Christenson RK, Day BN. Luteolytic effects of endometrial extracts in the pig. J Anim Sci 1972;34:620 –5. [3] Bazer FW, Geisert RD, Thatcher WW, Roberts RM. The establishment and maintenance of pregnancy. In: Cole DJA, Foxcroft, GA, editors. Control of Pig Reproduction, Butterworth Scientific, London 1982, pp. 227–53. [4] Gleeson AR, Thorburn GD, Cox RI. Prostaglandin F concentrations in the utero-ovarian venous plasma of the sow during the late luteal phase of the oestrous cycle. Prostaglandins 1974;5:521–9. [5] Waclawik HN, Jabbour A, Blitek BJ, Ziecik AJ. Estradiol17␤, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium, Endocrinology 2009;150:3823–32. [6] Niswender GD, Dzuik PJ, Kaltenbach CC, Norton HW. Local effects of embryo and uterus on corpora lutea in gilts. J Anim Sci 1970;30:225–34. [7] Ginther OJ. Internal regulation of physiological processes through local venoarterial pathways: a review. J Anim Sci 1974;39:550 – 64. [8] EMEA. The European Agency for the Evaluation of Medicinal Products. Dinoprost tromethamine report. Available at: http:// www.emea.europa.eu/pdfs/vet/mrls/dinoprost.pdf.

8

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

[9] EMEA. The European Agency for the Evaluation of Medicinal Products. Cloprostenol and R-cloprostenol summary report, April 1997. [10] Kral J, Mysikowa S, Bilek P, Borovicka A, Pichcova D, Seik B. Luteolytic effect of d-cloprostenol and its residue in milk and organs Biol Chem Vet 1989;25:293–300. [11] Re G, Badino P, Novelli, A, Vallisneria A, Girard GI. Specific binding of dl-cloprostenol and d-cloprostenol to PGF2␣ receptors in bovine corpus luteum and myometrial cell membranes. J Vet Pharm Ther 2008;17:455– 8. [12] Re G, Badino P, Novelli A, Vallisneri A, Girardi C. Specific binding of DL-cloprostenol and D-cloprostenol to PGF2alfa receptors in bovine corpus luteum and myometrial membranes. J Vet Pharmacol Therap 1994;17:455– 8. [13] Kimball FA, Lauderdale JW. Comparison of luteolytic effectiveness of several prostaglandin analogs in heifers and relative binding affinity for bovine luteal prostaglandin binding sites. Prostaglandins 1976;12:985–95. [14] Connor L, Phillips GD, Palmer WM. Effects of prostaglandin on the estrous cycle and hormone levels in the gilt. Can J Anim Sci 1976;56:661–9. [15] Anderson LE, Wu YL, Wiltbank MC. Prostaglandin F2a receptor in the corpus luteum: recent information on the gene, messenger ribonucleic acid, and protein. Biol Reprod 2001;64: 1041–7. [16] Anderson LL, Butcher RL, Melampy RM. Subtotal hysterectomy and ovarian function in gilts. Endocrinology 1961;69: 571– 80. [17] Horton EW, Poyser NL. Uterine luteolytic hormone: a physiological role for prostaglandin F2a. Physiol Rev 1976;56:595– 651. [18] Moeljono MP, Thatcher WW, Bazer FW, Frank M, Owens LJ, Wilcox CJ. A study of prostaglandin F2a as the luteolysin in swine: II. Characterization and comparison of prostaglandin F2a, estrogen and progestin concentration in utero-ovarian vein plasma of non pregnant and pregnant gilts. Prostaglandin 1977;14:543–55. [19] Gadsby JE, Balapure AK, BrittJH, Fitz TA. Prostaglandin F2 alfa receptors on enzyme dissociated pig luteal cells throughout the estrous cycle. Endocrinology 1990;126:787–95. [20] Gadsby JE, Lovdal JA, Britt JH, Fitz TA. Prostaglandin F2 alpha receptor concentrations in corpora lutea of cycling, pregnant, and pseudopregnant pigs. Biol Reprod. 1993;49:604 – 8. [21] Wiltbank MC, Shiaom TF, Bergfelt DR, Ginther OJ. Prostaglandin F2a receptors in the early bovine corpus luteum. Biol Reprod 1995;52:74 –78. [22] Wiltbank MC, Diskin MG, Flores JA, Niswender GD. Regulation of the corpus luteum by protein kinase C. II. Inhibition of lipoprotein–stimulated steroidogenesis by PGF2a. Biol Reprod 1990;42:239 – 45. [23] Wiltbank MC, Buthrie PB, Mattson MP, Kate SB, Niswender GD. Hormonal regulation of free intracellular calcium concentrations in small and large ovine cells. Biol Reprod 1989;41: 771– 8. [24] Diaz FJ, Crenshaw TD, Wiltbank MC. Prostaglandin F2a induces distinct physiological responses in porcine corpora lutea after acquisition of luteolytic capacity. Biol Reprod 2000;63: 1504 –12. [25] Tsai SJ, Wiltbank MC, Bodensteiner KJ. Distinct mechanisms regulate induction of messenger ribonucleic acid for prostaglandin G/H synthase-2, PGE (EP3) receptor, and PGF2␣ re-

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40] [41]

[42]

ceptor in bovine preovulatory follicles. Endocrinology 1996;137:3348 –55. Diaz FJ, Wiltbank MC. Acquisition of luteolytic capacity: changes in prostaglandin F2a regulation of steroid hormone receptors and estradiol biosynthesis in pig corpora lutea. Biol Reprod 2004;70:1333–9. Levy N, Kobayashi S, Roth Z, Wolfenson D, Miyamoto A, Meidan R. Administration of prostaglandin F2a during the early bovine luteal phase does not alter the expression of ET-1 and of its type A receptor: a possible cause for corpus luteum refractoriness. Biol Reprod 2000;63:377– 82. Diaz FJ, Wiltbank MC. Acquisition of luteolytic capacity involves differential regulation by prostaglandin F2a of genes involved in progesterone biosynthesis in the porcine corpus luteum. Domest Anim Endocrinol 2005;28:172– 89. Rexroad CE Jr, Guthrie HD. Prostaglandin F2 alpha and progesterone release in vitro by ovine luteal tissue during induced luteolysis. Adv Exp Med Biol 1979;112:639 – 44. Guthrie HD, Rexroad CE Jr, Bolt DJ. In vitro release of progesterone and prostaglandins F and E by porcine luteal and endometrial tissue during induced luteolysis. Adv Exp Med Biol 1979;112:627–32. Tsai SJ, Wiltbank MC. Prostaglandin F2␣ regulates distinct physiological changes in early and mid-cycle bovine corpora lutea. Biol Reprod 1998;58:346 –52. Slomczynska M, Krok M, Pierscinski A. Localization of the progesterone receptor in the porcine ovary. Acta Histochem 2000;102:183–91. Slomczynska M, Wozniak J. Differential distribution of estrogen receptor-beta and estrogen receptor-alpha in the porcine ovary. Exp Clin Endocrinol Diabetes 2001;109:238 – 44. Ford SP, Christenson LK. Direct effects of oestradiol-17B and prostaglandin E-2 in protecting pig corpora lutea from a luteolytic dose of prostaglandin F-2alfa. J Reprod Fertil 1991; 93:203–9. Jarry H, Einspanier A, Kanngiesser L, Dietrich M, Pitzel L, Holtz W, Wuttke W. Release and effects of oxytocin on estradiol and progesterone secretion in porcine corpora lutea as measured by an in vivo microdialysis system. Endocrinology 1990;126:2350 – 8. Gregoraszczuk EL, Oblonczyk K. Effect of a specific aromatase inhibitor on oestradiol secretion by porcine corpora lutea at various stages of the luteal phase. Reprod Nutr Dev 1996; 36:65–72. Duffy DM, Chaffin CL, Stouffer RL. Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. Endocrinology 2000;141:1711–17. Auletta FJ, Caldwell BV, Speroff L. Estrogen-induced luteolysis in the rhesus monkey: reversal with indomethacin. Prostaglandins 1976;11:745–52. Karsch FJ, Sutton GP. An intra-ovarian site for the luteolytic action of estrogen in the rhesus monkey. Endocrinology 1976; 98:553– 61. Conley AJ, Ford SP. Direct luteotrophic effect of oestradiol-17 beta on pig corpora lutea. J Reprod Fertil 1989;87:125–31. Qiu Y, Waters CE, Lewis AE, Langman MJ, Eggo MC. Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta. J Endocrinol 2002;174:369 –77. Kuranaga E, Kanuka H, Furuhata Y, Yonezawa T, Suzuki M, Nishihara M, Takahashi M. Requirement of the Fas ligand-

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

expressing luteal immune cells for regression of corpus luteum. FEBS Lett 2000;472:137– 42. Roughton SA, Lareu RR, Bittles AH, Dharmarajan AM. Fas and Fas ligand messenger ribonucleic acid and protein expression in the rat corpus luteum during apoptosis-mediated luteolysis. Biol Reprod 1999;60:797– 804. Taniguchi H, Yokomizo Y, Okuda K. Fas-Fas ligand system mediates luteal cell death in bovine corpus luteum. Biol Reprod 2002;66:754 –9. Silva PJ, Juengel JL, Turzillo AM, Rollyson MK, Niswender GD. Prostaglandin metabolism in the ovine corpus luteum: catabolism of prostaglandin F2␣ coincides with resistance of the corpus luteum to F2␣. Biol Reprod 2000;63:1229 –36. Arosh JA, Banu SK, Chapdelaine P, Madore E, Sirois J, Fortier MA. Prostaglandin biosynthesis, transport, and signalling in corpus luteum: a basis for autoregulation of luteal function, Endocrinology 2004;145:2551– 60. Goravanahally MP, Salem J, Yao EK, Inskeep EK, Flores JA. Differential gene expression in the bovine corpus luteum during transition from early phase to midphase and its potential role in acquisition of luteolytic sensitivity to prostaglandin F2 alpha. Biol Reprod 2009;80:980 – 8. Acosta TJ, Bah MB, Korzekwa A, Woclawek-Potocka I, Markiewicz W, Jaroszewski JJ, Okuda K, Skarzynski DJ. Acute changes in circulating concentrations of progesterone and nitric oxide and partial pressure of oxygen during prostaglandin F2alpha-induced luteolysis in cattle. J Reprod Dev 2009;55: 149 –55. Tenhagen BA, Kuchenbush S, Heuwieser W. Timing of ovulation and fertility of heifers after synchronization of oestrus with GnRH and prostaglandin F2␣. Reprod Dom Anim 2005; 40:62–7. De Rensis F, Peter A. The control of follicular dynamics by PGF2a, GnRH, hCG and estrus synchronization in cattle. Reprod Dom Anim 1999;34:49 –59. Menchaca A, Miller V, Gil J, Pinczak A, Laca M, Rubianes E. Prostaglandin F2alfa treatment associated with timed artificial insemination in ewes. Reprod Dom Anim 2004;39:352–5. Rubianes E, Menchaca A. The pattern and manipulation of ovarian follicular growth in goats. Anim Reprod Sci 2003;78: 271– 87. Bacci ML, Barazzoni AM, Forni A, Costerbosa GL. In situ detection of apoptosis in regressing corpus luteum of pregnant sow: evidence of an early presence of DNA fragmentation, Domest Anim Endocrinol 1996;13:361–72. Moeljono WW, Thatcher WW, Bazer FW, Frank M, Owens LJ, Wilcox CJ. A study of prostaglandin F2alpha as the luteolysin in swine: II. Characterization and comparison of prostaglandin F, estrogens and progestin concentrations in uteroovarian vein plasma of nonpregnant and pregnant gilts. Prostaglandins 1977;14:543–55. Tai HH, Ensor CM, Tong M, Zhou H, Yan F. Prostaglandin catabolizing enzymes. Prostaglandins Other Lipid Mediat 2002;68 – 69:483–93. Guthrie HD, Rexroad CE. Endometrial prostaglandin F release in vitro and plasma 13,14-dihydro-15-keto-prostaglandin F2␣ in pigs with luteolysis blocked by pregnancy, estradiol benzoate or human chorionic gonadotropin. J Anim Sci 1981;52; 330 –9. McCracken JA, Glew ME, Scaramuzzi RJ. Corpus luteum regression induced by prostaglandin in F2-alpha, J Clin Endocrinol Metab 1970;30:544 – 6.

9

[58] McCracken JA, Carlson JS, Glew ME, Goding JR, Baird DT, Gréen K, Samuelsson B. Prostaglandin F2 identified as a luteolytic hormone in sheep. Nat New Biol 1972;238:129 –34. [59] Inskeep EK, Murdoch WJ. Relation of ovarian functions to uterine and ovarian secretion of prostaglandins during the estrous cycle and early pregnancy in the ewe and cow. Int Rev Physiol 1980;22:325–56. [60] Thorburn GD, Cox RJ, Currie WB, Restall BJ, Schneider W. Prostaglandin F and progesterone concentrations in the uteroovarian venous plasma of the ewe during the oestrous cycle and early pregnancy. J Reprod Fertil 1973;18[Suppl]:151– 8 [61] Nancarrow CD, Buckmaster J, Chamley W, Cox RI, Cumming IA, Cummins L, Drinan JP, Findlay JK, Goding JR, Restall BJ, Schneider W, Thorburn GD. Hormonal changes around oestrus in the cow. J Reprod Fertil 1973;32:320 –1. [62] Peterson AJ, Fairclough RJ, Payne E, Smith JF. Hormonal changes around bovine luteolysis. Prostaglandins 1975;10: 675– 84. [63] Kindahl H, Edqvist LE, E. Granström E, Bane A. The release of prostaglandin F2alpha as reflected by 15-keto-13, 14-dihydroprostaglandin F2alpha in the peripheral circulation during normal luteolysis in heifers. Prostaglandins 1976;11:871– 8. [64] Schramm W, Bovaird L, Glew ME, Schramm G, McCracken JA. Corpus luteum regression induced by ultra-low pulses of prostaglandin F2 alpha. Prostaglandins 1983;26:347– 64. [65] Kindahl H, Lindelland JO, Edqvist LE. Release of prostaglandin F2␣ during the oestrus cycle. Acta Vet Scand (Suppl) 1981;77:143–58. [66] Diehl JR, Day BN. Effect of prostaglandin F2alfa on luteal function in swine. J Anim Sci 1974;39:392– 6. [67] Guthrie HD, Polge C. Luteal function and oestrus in gilts treated with a synthetic analogue of Prostaglandin F2␣ (ICI79.939) at various times during the oestrus cycle. J Reprod Fertil 1976;48:423–5. [68] Moeljono MPE, Bazer FW, Thatcher WW. A study of prostaglandin F2␣ as the luteolysin in swine. I. Effects of prostaglandin F2␣ in hysterectomized gilts. Prostaglandins 1976;11: 737– 43. [69] Bridges GA, Helser LA, Grum, DE, Mussard ML, Day ML. Decreasing the interval between GnRH and PGF2a from 7 to 5 days and lengthening proestrus increases timed-AI pregnancy rates in beef cows. Theriogenology 2008;69:843–51. [70] Kasimanickam R, Day ML, Rudolph JS, Hall JB, Whittier WD. Two doses of prostaglandin improve pregnancy rates to timed-AI in a 5-day progesterone-based synchronization protocol in beef cows. Theriogenology 2009;71:762–7. [71] Adams GP, Nasser LF, Bo GA, Garcia A, Del Campo MR, Mapletoft RJ. Superovulatory response of ovarian follicles of Wave 1 versus Wave 2 in heifers. Theriogenology 1994:42; 1103–13. [72] Whittier WD, Kasimanickam RK, Currin JF, Schramm HH, Vlcek M. Effect of timing of second prostaglandin F2alpha administration in a 5-day, progesterone-based Co-Synch protocol on AI pregnancy rates in beef cows. Theriogenology 2010;74:1002–9. [73] Estill CT, Britt JH, Gadsby JE. Repeated administration of prostaglandin F2␣ during the early luteal phase causes premature luteolysis in the pig. Biol Reprod 1993;49:181– 85. [74] Estill CT, Britt JH, Gadsby JE. Does increased PGF2␣ induce luteolysis during early diestrus in the pig? Prostaglandins 1995;49:255– 67.

10

F. De Rensis et al. / Theriogenology 77 (2012) 1–11

[75] Kuge T, Iwata H, Kuwayama T, Domeki I, Shioya Y, Monji Y. Induction of estrus by prostaglandin F2alfa administration in the vagina vestibules of miniature pig. J Reprod Dev 2006;52: 391– 6. [76] Cushman RA, Davis PE, Boonyaprakob U, Hedgpeth VS, Burns PJ, Britt JH. Technical note: use of slow-release estradiol and prostaglandin F2alpha to induce pseudopregnancy and control estrus in gilts. J Anim Sci 1999;77:2883–5. [77] Puglisi TA, Rampacek GB, Kraeling RR, Kiser TE. Corpus luteum susceptibility to prostaglandin F2 alpha (PGF2 alpha) luteolysis in hysterectomized prepuberal and mature gilts. Prostaglandins 1979;18:257– 64 [78] ten Haff W, Thacker PA, Kirkwood RN. Effect of injecting gonadotrophins during the luteal phase of the estrous cycle on the inter-estrus interval of gilts. Can J Anim Sci 2002;82: 457–9. [79] Davis DL, Blair RM. Studies of uterine secretions and products of primary cultures of endometrial cells in pigs. J Reprod Fertil [Suppl] 1993;48:143–55. [80] Sales KJ, Jabbour HN. Cyclooxygenase enzymes and prostaglandins in reproductive tract physiology and pathology. Prostaglandins Other Lipid Mediat 2003;71:97–117. [81] Christenson LK, Farley DB, Anderson LH, Ford SP. Luteal maintenance during early pregnancy in the pig: role for prostaglandin E2. Prostaglandins 1994;47:61–75. [82] Blitck A, Waclawik A, Kaczmarek MM, Kiewisk J, Ziecik AJ. Effect of estrus induction on prostaglandin content and prostaglandin synthesis enzyme expression in the uterus of early pregnant pigs. Theriogenology 2010;73:1244 –56. [83] Bazer FW, Thatcher WW. Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2alfa, by the uterine endometrium. Prostaglandins 1977;14:397– 400. [84] Spencer TE, Burghardt RC, Johnson GA, Bazer FW. Conceptus signals for establishment and maintenance of pregnancy. Anim Reprod Sci 2004;82– 83:537–50. [85] Kraeling RR, Rampacek GB, Ball GD. Estradiol inhibition of PGF2 luteolysis in the pig. J Anim Sci 1975;41[suppl 1]:363 [86] Meites FD, Webster HD, Young FW, Thorp J F and Hatch RN. Effects of corpora lutea removal and replacement with progesterone on pregnancy in goats, J Anim Sci 1951;10:411– 6. [87] Agarwal SP, Agarwal VK and Kanaujia AS. Steroid hormones in pregnant goats. Indian J Anim Sci 1998;58:1050 – 6. [88] Wango EO, Heap RB, Wooding FB. Progesterone and 5 betapregnanediol production by isolated foetal placental binucleate cells from sheep and goats. J Endocrinol 1991;129:283–9. [89] Perry JS, Heap RB, Burton RD, Gadsby JE. Endocrinology of the blastocyst and its role in the establishment of pregnancy. J Reprod Fertil (Suppl) 1976;25:85– 87. [90] Cates WF. Minimum daily exogenous progesterone requirement for implantation in the bovine species. PhD Thesis University of Minnesota 1963. [91] Wenkof MS. The use of prostaglandins in reproduction. Can Vet J 1975;4:100 –5. [92] Hammond D, Matty G. A farrowing management system using cloprostenol to control the time of parturition. Vet Rec 1980; 106:72–75. [93] Holtz W, Hartman FJ, Welp C. Induction of parturition in swine with prostaglandin analogue and oxytocin. Theriogenology 1983;19:583–92. [94] Guthrie HD. Control of time of parturition in pigs. J Reprod Fertil [Suppl] 1985;33:229 – 44.

[95] Cameron RDA, Kieran PJ, Martin I. The efficacy in inducing batch farrowing and the impact on sow behaviour of the prostaglandins cloprostenol and dinoprost. Proc 16th IPVS Congress, Melbourne, 2000; pp 386. [96] Keïta A, Driancourt MA, Pommier P, Pagot E, Hervé V. Induction of parturition in sows using luprostiol and cloprostenol: efficacy and safety evaluation. Proc 17th IPVS Congress, Ames, 2002: p. 475. [97] Balogh G, Bilkei G. Increasing the predictability of farrowing in swine with oxytocin or a parasympathomimetic agent after inducing parturition by cloprostenol. Pig J 2003;52:98 –105. [98] De Rensis F, Sottocorona M, Kirkwood RN. Effect of prostaglandin and dexamethasone injection on farrowing and piglet neonatal growth. Vet Rec 2002;14:330 –1. [99] Kaeoket K. The effect of dose and route of administration of R-Cloprostenol on the parturient response of sows. Reprod Dom Anim 2006;41:472– 6. [100] Kirkwood RN, Thacker PA, Aherne FX, Goonewardene LA. The effect of dose and route of administration of prostaglandin F2␣ on the parturient response of sows. J Swine Health Prod 1996;4:123– 6. [101] Kirkwood RN, Aherne FX. Improving the predictability of cloprostenol-induced farrowing in sows. Swine Health Prod 1998;6:219 –21. [102] Oxenreider SL, McClure RC, Day BN. Arteries and veins of the internal genitalia of female swine. J Reprod Fertil 1965;9: 19 –27. [103] Stefanczyk-Krzymowska S, Chlopek J, Grzegorzewski W, Radomski M. Local transfer of prostaglandin E2 into the ovary and its retrograde transfer into the uterus in early pregnant sows. Exp Physiol 2005;90:807–14. [104] Burne THJ, Murfitt PJE, Gilbert GL. Behavioural responses to intramuscular injections of prostaglandin F2␣ in female pigs. Pharmacol Biochem Behav 2000;66;789 –96. [105] Burne THJ, Murfitt PJE, Gilbert CL. Deprivation of straw bedding alters PGF2␣-induced nesting behaviour in female pigs, Appl Anim Behav Sci 2000;69:215–25. [106] Burne THJ, Murfitt PJF, Gilbert CK. Influence of environmental temperature on PGF2␣-induced nest building in female pigs. Appl Anim Behav Sci 2001;71:293–304. [107] Gilbert CL. Endocrine regulation of periparturient behaviour in pigs. Reprod (Suppl.) 2001;58:263–7. [108] Widowski TM, Curtis SE, Dziuk PJ, Wagner WC, Sherwood OD. Behavioral and endocrine responses of sows to prostaglandin F2 alpha and cloprostenol. Biol Reprod 1990;43: 290 –7. [109] Klopfenstein C, Farmer C, Martineau GP. Diseases of the mammary glands and lactation problems. In: Straw BE, Zimmerman JJ, Taylor DJ, eds. Diseases of Swine. 9th ed. Ames: Iowa State University Press 2006:833– 860. [110] De Passillé A, Rushen J, Foxcroft G, Aherne F, Schaefer A. Performance of young pigs: relationships with periparturient progesterone, prolactin and insulin of sows. J Anim Sci 1993; 71:179 – 84. [111] Gerjets I, Kemper N. Coliform mastitis in sows: A review. J Swine Health Prod 2009;17:97–105. [112] Kirkwood R. Influence of postpartum cloprostenol injection on sow and litter performance. Swine Health Prod 1999;7:121–2. [113] Einarsson S, Viring S, Lindell JO. The effect of prostaglandin F2 alpha and oxytocin on porcine myometrium in vitro. Zuchthygiene 1975;10:135–9.

F. De Rensis et al. / Theriogenology 77 (2012) 1–11 [114] Lorenzo J, Imaz M, Fernandez de Aragon J, Gilbert J, Simon X. Effect of LutalyseTM (DinolyticTM) sterile solution administered during the lactation period on several reproduction parameters of sows. Proc 12th IPVS Congress, The Hague 1992: p. 496. [115] Flaus L, Gilette G. Use of DinolyticTM sterile solution (PGF2a) in sows between 36 and 48 h post-farrowing. Proc 13th IPVS Congress, Bangkok, 1994; p. 382. [116] Morrow W, Britt J, Belschner A, Neeley G, O’Carrol J. Effect of injecting sows postpartum with prostaglandine F2␣ on neonatal survival. Proc 14th IPVS Congress, Bologna, 1996; p. 629. [117] Morrow W, Britt J, Belschner A, Neeley G, O’Carrol J. Effect of injecting sows with prostaglandin F2␣ immediately postpartum on subsequent reproductive performance. Swine Health Prod 1996;4:73–78. [118] Izeta-Mayorga J, Terminal O, Soto M, Ramos R, Ramirez F. PGF2␣(dinoprost tromethamine) 24 hrs post-farrowing and its effects on the weaning to service interval, fertility and the effects of antibiotic treatments in sows of different parities. Proc. 15th IPVS Congress, Birmingham, 1988; p. 89. [119] Lauderdale J, Hanson B, Chenault J. The effect of injecting 2 ml LutalyseTM/DinolyticTM sterile solution (dinoprost tromethamine) into post-partum sows on number of piglets born and born alive per litter in the subsequent farrowing. Proc. 15th IPVS Congress, Birmingham, 1988; p. 215. [120] Koketsu Y, Dial GD, King VL. Returns to service after mating and removal of sows for reproductive reasons from commercial swine farms. Theriogenology 1997;47:1347– 63. [121] Koketsu Y, Dial G. Interactions between the associations of parity, lactation length, and weaning-to-conception interval with subsequent litter size in swine herds using early weaning. Prev Vet Med 1998;37:113–20. [122] Schoffield S, Kitwood S, Phillips J. The effects of a post partum injection of prostaglandin F2␣ on return to oestrus and pregnancy rates in dairy cows. Vet J 1999;157:172–7. [123] Melendez P, McHale J, Bartolome J, Archbald L, Donovan G. Uterine involution and fertility of Holstein cows subsequent to early postpartum PGF2alfa treatment for acute puerperal metritis. J Dairy Sci 2004;87:3238 – 46. [124] Chenault J, Hanson B, Gilette G, Lasvergeres F. Reduction in the days from weaning to oestrus and fertile service in sows

[125]

[126]

[127]

[128] [129]

[130]

[131]

[132]

[133]

[134]

[135]

11

following a single post-partum injection of Lutalyse®/DinolyticTM sterile solution. Proc 14th IPVS Congress, Bologna, 1996; p. 628. Vanderhaeghe C, Dewulf J, Daems A, Van Soom A, de Kruif A, Maes D. Influence of postpartum cloprostenol treatment in sows on subsequent reproductive performance under field conditions. Reprod Dom Anim 2008;43:484 –9. Ainsworth L, Tsang BK, Downey BR, Marcus GJ. The synthesis and action of stroids and prostaglandins during follicular maturation in the pig. J Reprod Fertil [suppl] 1990;40:137–50. Claus R. Physiological role of seminal components in the reproductive tract of the female pig. J Reprod Fertil [Suppl] 1990;40:117–31. Srikandakumar AD, Downey BR. Induction of ovulation in gilts with cloprostenol. Theriogenology 1989;32:445–9. Ainsworth L, Baker RD, Armstrong DT. Pre-ovulatory changes in follicular fluid prostaglandin F levels in swine. Prostaglandins 1975;9:915–25. Pena F, Dominguez JC, Alegre B, Pelaez J. Effect of vulvomucosal injection of PGF2␣ at insemination on subsequent fertility and litter size in pigs under field conditions. Anim Reprod Sci 1998;52:63– 69. Pena FJ, Gil MC, Pena F. Effect of vulvomucosal injection of D-cloprostenol at weaning and at insemination on reproductive performances of sow during the low fertility summer season under field condition. Anim Reprod Sci 2001;68:77– 83. Pena FJ, Dominguez JC, Pelaez J, Alegre B. Intrauterine infusion of PGF2a at insemination enhances reproductive performance of sows during the low fertility season. Vet J 2000; 159:259 – 61. Horvat G, Bilkei G. Exogenous prostaglandin F2␣ at the time of ovulation improves reproductive efficiency in repeat breeder sows. Theriogenology 2003;59:1479 – 84. Kos M., Bilkei G. Prostaglandin F2a supplemented semen improves reproductive performance in artificially inseminated sows. Anim Reprod Sci 2004;80:113–20. Langendijk P, Bouwman EG, Kidson A, Kirkwood RN, Soede NM, Kemp B. Functions of myometrial activity in sperm transport through the genital tract and fertilisation in sows. Reproduction 2002;123:683–90.