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Terminologies for the pre-attachment bovine embryo
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Theriogenology 76 (2011) 1373–1379 www.theriojournal.com
Review
Terminologies for the pre-attachment bovine embryo Jaana Peippoa, Zoltan Machatyb, Augustine Peterc,* a
MTT Agrifood Research Finland, Biotechnology and Food Research, FI-31600 Jokioinen, Finland b Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA c Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, USA Received 22 October 2010; received in revised form 9 June 2011; accepted 16 June 2011
Abstract There are numerous publications regarding bovine embryos, ranging from descriptions of their appearance and development to emerging techniques in the field of assisted reproductive technology (ART). Concurrently, several specialized terms have been developed to describe the bovine embryo. Many of these terms are simple, some are difficult to understand and use, and others are antiquated and may not be scientifically accurate. For example, use of terms such as syngamy, conception rate, implantation and embryo resorption should be revisited. This review presents a brief overview of current knowledge regarding the pre-attachment period of the bovine embryo and attempts to define the terms. In this process, conventional terminology is presented, and contemporary and novel terms are proposed from a biological perspective. © 2011 Elsevier Inc. All rights reserved. Keywords: Embryo; Pre-implantation; Pre-attachment; Terminology; Cattle
Contents 1. 2.
Introduction ............................................................................................................................ Embryonic period ..................................................................................................................... 2.1. Fertilization ................................................................................................................... 2.2. Timing discrepancies between in vivo and in vitro procedures ...................................................... 2.3. Period of pre-attachment .................................................................................................... 2.4. Developmental processes ................................................................................................... 2.5. Attachment .................................................................................................................... 3. Summary ............................................................................................................................... Acknowledgments .................................................................................................................... References ...................................................................................................................................
1. Introduction Pioneering work in bovine embryology was conducted in the mid-1900s [1–3]. Further work in this area provided substantial insight into the complexity of * Corresponding author. Tel.: 765-494-5808; fax: 765-496-1108. E-mail address: [email protected] 0093-691X/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.theriogenology.2011.06.018
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form and function of bovine embryos [4,5]; this allowed phenomenal expansion in the knowledge of bovine embryos, resulting in excellent research and reviews in this subject area [6 – 8]. Various embryo manipulations and rapid advances in embryo transfer prompted further reviews [9 –12]. Commercial availability of embryo transfer in the early 1980s [13] gave impetus for the growth of as-
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J. Peippo et al. / Theriogenology 76 (2011) 1373–1379
sisted reproductive technology (ART). A noteworthy step in ART was development of ovarian superstimulation (superovulation) regimens [14], which enabled collection of oocytes and multiple ovulation embryo transfer protocols. In 1981, the first live calf was produced by in vitro fertilization (IVF), whereas the first live calf from an oocyte matured in vitro (IVM) was reported in 1986. Three years later, the first live calf was produced by IVM/IVF. The developmental timeline in ART has been thoroughly reviewed [13]. These in vitro techniques gave new opportunities for cattle producers, particularly in the dairy industry, to overcome infertility and to increase dissemination of high genetic merit animals. During the last 30 y, developments in ART and refinement in embryo cryopreservation resulted in large-scale international commercialization of bovine embryo transfer [15]; that ⬎ 500,000 embryos are produced annually [15] illustrates the extent and value of this technology. Developments in bovine ART are more substantial and in much broader use than those in any other non-human species. Further, based on these advances, cattle are often used as a model to study ovarian function and embryogenesis. In this regard, bovine embryos have many characteristics that make them a good model for the human. For example, cattle and humans are both typically monoovulators, and their embryos are similar in size and energy metabolism [16,17]. Along with development, issues related to hygiene and prevention of the spread of diseases were addressed from the use of components extracted from biological sources (e.g., serum, BSA, and semen) in ART programs. Recommendations were made from a biosecurity perspective for embryo transfer programs [18]. The threat of disease spread via embryo transfer [19] and the role of protection offered by the zona pellucida in preventing transmission of viral agents in embryo transfer programs [20] were discussed. In this context, studies were targeted on transmission of specific viral agents, including enzootic bovine leucosis to recipients of bovine embryos [21]. Further, the impact of nutrition, climate, and embryonic mortality on ART, and the impact of ART in the developing world were studied and reviewed. For example, special efforts were made to understand the role of nutrition and management in beef cattle embryo production [22]. Information on embryonic mortality [23–26] and manipulation-induced changes in embryos [27–29] were provided. The role of uterine inflammation on embryo growth was examined in a creative way [30]. The difference in resistance to heat shock between Bos taurus and Bos
indicus was characterized [31]. The economic impact of embryo transfer in the developing world [32] has been discussed. Undoubtedly, further developments in the area of bovine embryos will be the impetus for additional reviews to document growth in knowledge in this area. Recently, we suggested defining and adopting terms used in bovine reproduction that are clear, precise and understandable, and available in a single source, to make the exchange of clinical and research information and outcomes more effective, safe and economical [33]. As part of a proposed series of reviews, the earlier report defined healthy and diseased conditions of the bovine ovary, primarily during the estrous cycle [33]. The present review will focus on terms and current understanding of the processes involved in bovine embryos prior to attachment. A supplemental review on the post-attachment bovine embryo is planned. 2. Embryonic period The term embryo describes the products of fertilization until major organogenesis is completed. In cattle, the period of the embryo extends to 42– 45 d of pregnancy [4,5,34,35]. These reports laid the foundation for terms applied to bovine embryos and defined them based on in vivo development. The headings for discussion are fertilization, timing discrepancies between in vivo and in vitro procedures, period of pre-attachment, developmental processes, and attachment. 2.1. Fertilization Fertilization refers to the union of male and female gametes to form a zygote, a process that begins with the entry of a spermatozoon into a secondary oocyte. It is completed when the nuclear envelopes of the male and female pronuclei break down and the chromatin condenses into chromosomes which are oriented on a common mitotic spindle. As in other mammals, in cattle there is close apposition of pronuclei, followed by pronuclear membrane breakdown without fusion [36]. Hence the use of the term syngamy to describe the process of fertilization in cattle is discouraged. Although the term ‘conception’ is used in the place of fertilization, the latter is the preferred term. This leads to the next issue, the term ‘fertilization rate’. It refers to the percentage of oocytes fertilized, a term that can be difficult to apply in in vivo situations, except in superstimulation regimens that result in multiple embryos. It has application in in vitro situations and is a measure of two traits, i.e., it can mean either how
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quickly fertilization occurs or the percentage of oocytes fertilized. However, it generally refers to the latter trait. Apart from superstimulation regimens in in vivo situations (number of embryos harvested), use for this term for in vivo situation is limited in cattle. In some areas ‘conception rate’ and non-return rate are used interchangeably, however, these two are not synonymous, since inevitably some cattle which were not serviced were not pregnant [37]. Since ‘fertilization’ is preferred over ‘conception’, fertilization rate can be used instead of conception rate. However, it should be mentioned that fertilization rate and pregnancy rate have distinct meanings; fertilization rate relates and indirectly attests to the quality of oocyte or spermatozoa, which enables the process of fertilization to be successfully completed. Pregnancy rate relates to the quality of the ensuing embryo. Since pregnancy is diagnosable in cattle (which also accounts for fertilization rate) the term pregnancy rate is preferred to fertilization rate. The term conceptus is similar to the word conception and refers to all the products of conception, including embryo, fetus, fetal membranes, and their contents [34]. As discussed, the use of the term conception has limited application, which is also applicable to the term conceptus. It gets further complicated since the term conceptus refers to many structures. Therefore, we suggest that the products of fertilization (embryo, fetus, fetal membranes and their contents) should be designated separately with their proper names, although the all-encompassing term conceptus can be appropriate. 2.2. Timing discrepancies between in vivo and in vitro procedures The advent of in vitro production of embryos generated challenges and inconsistencies regarding the timing of events in the process of development. Important issues are divergence in calculation of Day 0 and discrepancies in the time at which milestones in embryonic development are reached. The latter discrepancy is due to production of heterogeneous cohorts of embryos and inherent differences in embryonic micro-environment. Consequently, these factors influence developmental kinetics of embryos, leading to unsynchronized cell divisions among individual embryos; this accounts for, at least in part, the wide range in timing regarding developmental processes of cattle embryos (see section 2.4.). 2.3. Period of pre-attachment The period before attachment is correctly referred to as the pre-attachment stage [8]. The focus of this re-
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view is on events prior to the beginning of attachment or the period prior to the initiation of the process of attachment. It will be referred to as the early embryonic period, a term that gave rise to the origin of the term ‘early embryonic death’ used widely to describe the process of embryonic loss or mortality during this period [38,39]. The fate of the dead early embryo is not known, whether it is absorbed by the endometrium or expelled vaginally has been speculated but not clearly demonstrated. However, the latter phenomenon was observed in the case of post-attachment embryos [40]. In this context, use of the terms embryo reabsorption or resorption is discouraged, since it may not be the process that is actually taking place (American College of Theriogenologists listserv communication). The stage of the early embryo is very important from two perspectives. The first of these is ‘maternal recognition of pregnancy,’ a crucial step in the successful establishment of pregnancy. The discussion on this topic is beyond the scope of this review and has already been reviewed [29,41– 43]. The second issue is that this period is critical and important from the perspective of embryo manipulation. Not much is known about the growth of twin embryos during this period, since such studies have been conducted after 25–28 d post insemination [44,45]. 2.4. Developmental processes The early embryonic period includes the following developmental processes: cleavage, compaction, blastulation, expansion, hatching, and elongation (Fig. 1). Successful completion of these sequential events is important for establishment of pregnancy. Rather than defining different stages during the preattachment period [7], we will consider various processes involved in this period and recognize the timing at which the developmental stage was found. Existing knowledge in the pre-attachment period of embryo is based on observation of embryos collected from the oviduct and/or uterus or embryos that are derived from in vitro studies. The staging of the timing of various events may not be accurate, since observations usually are not from the same animal. There has been relatively little concerted study on the developing embryo (and fetus), partly because in vivo studies are difficult and expensive [46]. Observations and measurements require surgical intervention or post mortem recovery of material [46]. These approaches disrupt and interrupt the very processes under scrutiny [46]. Few studies lend themselves to non-invasive, non-terminal, or sequential methods [46]. Although in vitro studies have
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D 12
D 7.5-11
D 7-8
D6
D5
Ovary
Fertilization Cleavage Compaction Expansion Blastulation
Hatching
Oviduct Elongation
Uterus
Fig. 1. Terms and concepts regarding bovine embryos during the pre-attachment period.
provided more information in this area, it is noteworthy that there were differences in the growth pattern of embryo(s) from superstimulated and non-superstimulated cattle [47]. In addition, differences in the growth rate between in vivo and in vitro grown embryos can be ascribed to the ‘quiet embryo hypothesis’ [17,48,49]. According to this hypothesis, viable pre-attachment embryos operate at metabolite or nutrient turnover rates distributed within lower ranges than those of their less viable counterparts. Cleavage refers to the process of cell division that occurs in a fertilized oocyte in the oviduct as it moves toward the uterus [50]. These cell divisions result in successively smaller cells. After cell divisions are completed, the cells of the embryo changes
from a spherical to a polygonal shape, during a process called compaction, which occurs at approximately Day 5 [51]. Blastulation refers to the formation of a cavity eventually leading to the expansion of the embryo. Blastulation is believed to occur at ⬃Day 6 [52]. However, blastulation does not occur until Day 7 in non-superstimulated cows and half a day earlier in superstimulated cows. Expansion refers to an increase in diameter, resulting in thinning of the zona pellucida, which begins around Days 7– 8. Hatching follows expansion, which is highly variable (Days 7.5–11) [53]. This is followed by the process of elongation that starts at approximately Day 12 and ends at approximately Day 18 [50,54,55]. The days given for the above processes
Table 1 Summary of terms in pre-attachment bovine embryos. Day 0 Fertilization Fertilization rate Attachment Period of pre-attachment Early embryo Early embryonic death Cleavage Compaction Blastulation Expansion Hatching Elongation
Day of insemination or breeding or onset of estrus This term is preferred to the term conception Pregnancy rate will replace this term for an in vivo situation Attachment will replace the term implantation From Days 0 to 16 [56] Corresponds to the period before attachment Death of the embryo during the period prior to attachment Process of cell division occurring in the zygote through the 16 cell-stage [57] Change of embryo cells from spherical to polygonal Formation of a cavity within the embryo Increases in the diameter of the embryo resulting in thinning of the zona pellucida [58] Release from the zona pellucida—timing is highly variable [53] Embryo reaches approximately 12 mm [59]
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are only approximations, since Day 0 was not uniform in these studies and may not be accurate since embryos were observed from different animals or in different in vitro conditions. Table 1 has the summary of terms. 2.5. Attachment Among the events that occur during the embryonic period, the most critical and culminating event leading to a successful pregnancy is ‘implantation’. The term implantation refers to the process by which the embryo implants or inserts itself to the endometrium. The term attachment is preferred to the term implantation, since there is no penetration or insertion of the bovine embryo into the endometrium [35] as occurs in rodents and primates. Partly, this confusion arose with borrowing terminology used in mouse embryology (mice have a distinctly different window of development compared to cattle; however, pre-hatching development in cattle is comparable to mice pre-implantation development). In cattle, the term ‘attachment’ aptly describes the processes, since only fetal membranes are getting ‘attached’ to the endometrium with the embryo located within the fetal membranes [4,5,60,61]. In support of this argument, the classical work by Chang [3] suggested that the real attachment (the intricate tissue connection between the cotyledons and caruncles) is established between 40 –50 d of pregnancy. The reason for such a range for the timing of attachment is understandable since the study used abbatoir-derived materials. Further, defining the day of ovulation (Day 0) as determined by the presence of a dark-red colored, medium sized CL in one of the ovaries could have resulted in this wide range. It was also reported [60] that the chorio-allantoic membrane attaches to the endometrium between 30 and 35 d after ovulation (confirmed by transrectal palpation). Although the time at which the attachment process is completed is somewhat known, the time this process begins is not clear. It was suggested that the process of attachment begins around Day 16 [56]; this was supported by ultrastructural studies [62]. Discussions regarding placentation are beyond the scope of this work and will be included in another review. 3. Summary We propose that nomenclature be updated and revised for events associated with bovine reproduction, as suggested in human reproductive medicine
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[63,64]. As the second of a series of reviews, this mini-review is focused on defining the developmental stages in a bovine pre-attachment embryo and appropriate terminology. In this process, we suggested revising certain terminology and deleting other terms. The latter terms are syngamy, conception, implantation, and embryo resorption. It is expected that this review will make the exchange of information and outcomes more effective and economical. Further reviews will define and describe the processes of a post-attachment embryo and certain aspects of bovine pregnancy, from the perspective of scientists working with cattle. Acknowledgments The authors gratefully acknowledge the valuable assistance provided by Don Bergfeldt in reviewing and contributing to this review. References [1] Winters LM, Green WW, Comstock RE. Prenatal development of the bovine. Minn Agr Exp Sta Tech Bull 1942;151:1–50. [2] Hamilton WJ, Laing JA. Development of the egg of the cow up to the stage of blastocyst formation. J Anat 1946;80:194 –204. [3] Chang MC. Development of bovine blastocyst with a note on implantation. Anat Rec 1952;113:143– 61. [4] Marion GB, Gier HT. The process of placentation in the bovine. J Anim Sci 1958;17:1216 –17 (Abstr.). [5] Greenstein JS, Foley RC. Early embryology of the cow. J Dairy Sci 1958;41:409 –21. [6] Massip A, Mulnard P, Vanderzwalmen P, Hanzen C, Ectors F. The behaviour of cow blastocyst in vitro: cinematographic and morphometric analysis. J Anat 1982;134:399 – 405. [7] Lindner GM, Wright RW Jr. Bovine embryo morphology and evaluation. Theriogenology 1983;20:407–16. [8] Betteridge KJ, Fléchon J-E. The anatomy and physiology of pre-attachment bovine embryos. Theriogenology 1988;29: 155– 87. [9] Barros CM, Nogueira MF. Embryo transfer in Bos indicus cattle. Theriogenology 2001;56:1483–96. [10] Hasler JF. The current status and future of commercial embryo transfer in cattle. Anim Reprod Sci 2003;79:245– 64. [11] Greve T, Callesen H. Embryo technology: implications for fertility in cattle. Rev Sci Tech 2005;24:405–12. [12] Lonergan P. State-of-the-art embryo technologies in cattle. Soc Reprod Fertil Suppl 2007;64:315–25. [13] Moore K, Thatcher WW. Major advances associated with reproduction in dairy cattle. J Dairy Sci 2006;89:1254 – 66. [14] Seidel GE Jr. Superovulation and embryo transfer in cattle. Science 1981;211:351– 8. [15] Mapletoft RJ, Hasler JF. Assisted reproductive technologies in cattle: a review. Rev Sci Tech 2005;24:393– 403. [16] Thompson JG, Partridge RJ, Houghton FD, Cox CI, Leese HJ. Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos. J Reprod Fertil 1996;106:299 –306.
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J. Peippo et al. / Theriogenology 76 (2011) 1373–1379
[17] Baumann CG, Morris DG, Sreenan JM, Leese HJ. The quiet embryo hypothesis: molecular characteristics favoring viability. Mol Reprod Dev 2007;74:1345–53. [18] Givens MD, Marley SD. Approaches to biosecurity in bovine embryo transfer programs. Theriogenology 2008; 69:129 –36. [19] Sutmoller P, Wrathall AE. The risks of disease transmission by embryo transfer in cattle. Rev Sci Tech 1997;16:226 –39. [20] Van Soom A, Wrathall AE, Herrler A, Nauwynck HJ. Is the zona pellucida an efficient barrier to viral infection? Reprod Fertil Devel 2010;22:21–31. [21] Wrathall AE, Simmons HA, Van Soom A. Evaluation of risks of viral transmission to recipients of bovine embryos arising from fertilisation with virus-infected semen. Theriogenology 2006;65:247–74. [22] Jones AL, Lamb GC. Nutrition, synchronization, and management of beef embryo transfer recipients. Theriogenology 2008; 69:107–15. [23] Wathes DC. Embryonic mortality and the uterine environment. J Endocrinol 1992;134:321–5. [24] García-Ispierto I, López-Gatius F, Santolaria P, Yániz JL, Nogareda C, López-Béjar M, De Rensis F. Relationship between heat stress during the peri-implantation period and early fetal loss in dairy cattle. Theriogenology 2006;65:799 – 807. [25] Diskin MG, Morris DG. Embryonic and early foetal losses in cattle and other ruminants. Reprod Domest Anim 2008;43: 260 –7. [26] Alexopoulos NI, Maddox-Hyttel P, Tveden-Nyborg P, D’Cruz NT, Tecirlioglu TR, Cooney MA, Schauser K, Holland MK, French AJ. Developmental disparity between in vitro-produced and somatic cell nuclear transfer bovine days 14 and 21 embryos: implications for embryonic loss. Reproduction 2008;136: 433– 45. [27] Young LE, Sinclair KD, Wilmut I. Large offspring syndrome in cattle and sheep. Rev Reprod 1988;3:155– 63. [28] Lazzari G, Wrenzycki C, Herrmann D, Duchi R, Kruip T, Niemann H, Galli C. Cellular and Molecular deviations in bovine in vitro-produced embryos are related to the large offspring syndrome. Biol Reprod 2002;67:767–75. [29] Farin CE, Farmer WT, Farin PW. Pregnancy recognition and abnormal offspring syndrome in cattle. Reprod Fertil Dev 2010; 22:75– 87. [30] Hill J, Gilbert R. Reduced quality of bovine embryos cultured in media conditioned by exposure to an inflamed endometrium. Aust Vet J 2008;86:312– 6. [31] Hansen PJ. To be or not to be— determinants of embryonic survival following heat shock. Theriogenology 2007;68 Suppl 1:S40 – 8. [32] Madan ML. Animal biotechnology: applications and economic implications in developing countries. Rev Sci Tech 2005;1:127–39. [33] Peter AT, Levine H, Drost M, Bergfeldt DR. Compilation of classical and contemporary terminology used to describe morphological aspects of ovarian dynamics in cattle. Theriogenology 2009;71:1343–57. [34] Committee on bovine reproductive nomenclature. Recommendations for standardizing bovine reproductive terms. Cornell Vet 1972;62:216 –36. [35] Roberts SJ. Gestation period: embryology, fetal membranes and placenta. In: Roberts SJ, editor. Veterinary Obstetrics and Genital Diseases (Theriogenology). Ann Arbor: Edward Brothers, 1986, pp. 38 –50.
[36] Longo FJ. Fertilization: a comparative ultrastructural review. Biol Reprod 1973;9:149 –215. [37] Bartlett DE. Theriogenology: From concept to actuality. Theriogenology 1985;2:131– 45. [38] Dunne LD, Diskin MG, Sreenan JM. Embryo and foetal loss in beef heifers between day 14 of gestation and full term. Anim Reprod Sci 2000;58:39 – 44. [39] Berg DK, van Leeuwen J, Beaumont S, Berg M, Pfeffer PL. Embryo loss in cattle between days 7 and 16 of pregnancy. Theriogenology 2010;73:250 – 60. [40] Kastelic JP, Ginther OJ. Fate of conceptus and corpus luteum after induced embryonic loss in heifers. J Am Vet Med Assoc 1989;194:922–28. [41] Thatcher WW, Meyer MD, Danet-Desnoyers G, Maternal recognition of pregnancy. J Reprod Fertil Suppl 1995;49:15–28. [42] Demmers KJ, Derecka K, Flint A. Trophoblast interferon and pregnancy. Reproduction. 2001;121:41–9. [43] Wolf E, Arnold GJ, Bauersachs S, Beier HM, Blum H, Einspanier R, Fröhlich T, Herrler A, Hiendleder S, Kölle S, Prelle K, Reichenbach HD, Stojkovic M, Wenigerkind H, Sinowatz F. Embryo-maternal communication in bovine—strategies for deciphering a complex cross-talk. Reprod Domest Anim 2003;38: 276 – 89. [44] Silva-del-Río N, Colloton JD, Fricke PM. Factors affecting pregnancy loss for single and twin pregnancies in a high-producing dairy herd. Theriogenology 2009;71:1462–71. [45] López-Gatius F, García-Ispierto I, Hunter RH. Factors affecting spontaneous reduction of corpora lutea and twin embryos during the late embryonic/early fetal period in multiple ovulating dairy cows. Theriogenology 2010;73:293–9. [46] Dziuk PJ. Embryonic development and fetal growth. Anim Reproduction Science 1992;28:299 –308. [47] Sartori R, Bastos MR, Wiltbank MC. Factors affecting fertilisation and early embryo quality in single- and superovulated dairy cattle. Reprod Fertil Dev 2010; 22:151– 8. [48] Leese HJ. Quiet please, do not disturb: a hypothesis of embryo metabolism and viability. Bioessays 2002;24:845–9. [49] Leese HJ, Baumann CG, Brison DR, McEvoy TG, Sturmey RG. Metabolism of the viable mammalian embryo: quietness revisited. Mol Hum Reprod 2008;12:667–72. [50] Imakawa K, Chang KT, Christenson RK. Pre-implantation conceptus and maternal uterine communications: molecular events leading to successful implantation. Reprod Dev 2004; 50:155– 69. [51] Van Soom A, Van Vlaenderen I, Mahmoudzadeh AR, Deluyker H, de Kruif A. Compaction rate of in vitro fertilized bovine embryos related to the interval from insemination to first cleavage. Theriogenology 1992;38:905–19. [52] Holm P, Shukri NN, Vajta G, Booth P, Bendixen C, Callesen H. Developmental kinetics of the first cell cycles of bovine in vitro produced embryos in relation to their in vitro viability and sex. Theriogenology 1998;50:1285–99. [53] Brandão DO, Maddox-Hyttel P, Løvendahl P, Rumpf R, Stringfellow D, Callesen H. Post hatching development: a novel system for extended in vitro culture of bovine embryos. Biol Reprod 2004;71:2048 –55. [54] Kastelic JP, Curran S, Pierson RA, Ginther OJ. Ultrasonic evaluation of the bovine conceptus. Theriogenology 1988; 29:39 –54. [55] Blomberg L, Hashizume K, Viebahn C. Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation. Reproduction 2008:135;181–95.
J. Peippo et al. / Theriogenology 76 (2011) 1373–1379 [56] Bertolini M, Beam SW, Shim H, Bertolini LR, Moyer AL, Famula TR and Anderson GB. Growth, development and gene expression by in vivo- and in vitro-produced Day 7 and Day 16 bovine embryos. Mol Reprod Dev 2002; 63:318 –28. [57] Ushijima H, Akiyama K, Tajima T. Classification of morphological changes based on the number of cleavage divisions in bovine embryos. J Reprod Dev 2009;55:83–7. [58] Alexopoulos NI, French AJ. The prevalence of embryonic remnants following the recovery of post-hatching bovine embryos produced in vitro or by somatic cell nuclear transfer. Anim Reprod Sci 2009;114:43–53. [59] Vejlsted M, Du Y, Vajta G, Maddox-Hyttel P. Post-hatching development of the porcine and bovine embryo – defining criteria for expected development in vivo and in vitro. Theriogenology 2006;65:153– 65.
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[60] Melton AA, Berry RO, Butler OD. The interval between the time of ovulation and attachment of the bovine embryo. J Anim Sci 1951;10:993–1005. [61] Greenstein JS, Murray RW, Foley RC. Observations on the morphogenesis and histochemistry of the bovine preattachment placenta between 16 and 33 days of gestation. Anat Rec 1958; 132:321– 41. [62] Wathes DC, Wooding FB. An electron microscopic study of implantation in the cow. Am J Anat 1980;159:285–306. [63] Farquharson RG, Jauniaux E, Exalto N. Updated and revised nomenclature for description of early pregnancy events. Hum Reprod 2005;20:3008 –11. [64] Hughes LA. Disorders of sex development: a new definition and classification. Best Pract Res Clin Endocrinol Metab 2008;22: 119 –34.
Theriogenology 76 (2011) 1373–1379 www.theriojournal.com
Review
Terminologies for the pre-attachment bovine embryo Jaana Peippoa, Zoltan Machatyb, Augustine Peterc,* a
MTT Agrifood Research Finland, Biotechnology and Food Research, FI-31600 Jokioinen, Finland b Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA c Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, USA Received 22 October 2010; received in revised form 9 June 2011; accepted 16 June 2011
Abstract There are numerous publications regarding bovine embryos, ranging from descriptions of their appearance and development to emerging techniques in the field of assisted reproductive technology (ART). Concurrently, several specialized terms have been developed to describe the bovine embryo. Many of these terms are simple, some are difficult to understand and use, and others are antiquated and may not be scientifically accurate. For example, use of terms such as syngamy, conception rate, implantation and embryo resorption should be revisited. This review presents a brief overview of current knowledge regarding the pre-attachment period of the bovine embryo and attempts to define the terms. In this process, conventional terminology is presented, and contemporary and novel terms are proposed from a biological perspective. © 2011 Elsevier Inc. All rights reserved. Keywords: Embryo; Pre-implantation; Pre-attachment; Terminology; Cattle
Contents 1. 2.
Introduction ............................................................................................................................ Embryonic period ..................................................................................................................... 2.1. Fertilization ................................................................................................................... 2.2. Timing discrepancies between in vivo and in vitro procedures ...................................................... 2.3. Period of pre-attachment .................................................................................................... 2.4. Developmental processes ................................................................................................... 2.5. Attachment .................................................................................................................... 3. Summary ............................................................................................................................... Acknowledgments .................................................................................................................... References ...................................................................................................................................
1. Introduction Pioneering work in bovine embryology was conducted in the mid-1900s [1–3]. Further work in this area provided substantial insight into the complexity of * Corresponding author. Tel.: 765-494-5808; fax: 765-496-1108. E-mail address: [email protected] 0093-691X/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.theriogenology.2011.06.018
1373 1374 1374 1375 1375 1375 1377 1377 1377 1377
form and function of bovine embryos [4,5]; this allowed phenomenal expansion in the knowledge of bovine embryos, resulting in excellent research and reviews in this subject area [6 – 8]. Various embryo manipulations and rapid advances in embryo transfer prompted further reviews [9 –12]. Commercial availability of embryo transfer in the early 1980s [13] gave impetus for the growth of as-
1374
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sisted reproductive technology (ART). A noteworthy step in ART was development of ovarian superstimulation (superovulation) regimens [14], which enabled collection of oocytes and multiple ovulation embryo transfer protocols. In 1981, the first live calf was produced by in vitro fertilization (IVF), whereas the first live calf from an oocyte matured in vitro (IVM) was reported in 1986. Three years later, the first live calf was produced by IVM/IVF. The developmental timeline in ART has been thoroughly reviewed [13]. These in vitro techniques gave new opportunities for cattle producers, particularly in the dairy industry, to overcome infertility and to increase dissemination of high genetic merit animals. During the last 30 y, developments in ART and refinement in embryo cryopreservation resulted in large-scale international commercialization of bovine embryo transfer [15]; that ⬎ 500,000 embryos are produced annually [15] illustrates the extent and value of this technology. Developments in bovine ART are more substantial and in much broader use than those in any other non-human species. Further, based on these advances, cattle are often used as a model to study ovarian function and embryogenesis. In this regard, bovine embryos have many characteristics that make them a good model for the human. For example, cattle and humans are both typically monoovulators, and their embryos are similar in size and energy metabolism [16,17]. Along with development, issues related to hygiene and prevention of the spread of diseases were addressed from the use of components extracted from biological sources (e.g., serum, BSA, and semen) in ART programs. Recommendations were made from a biosecurity perspective for embryo transfer programs [18]. The threat of disease spread via embryo transfer [19] and the role of protection offered by the zona pellucida in preventing transmission of viral agents in embryo transfer programs [20] were discussed. In this context, studies were targeted on transmission of specific viral agents, including enzootic bovine leucosis to recipients of bovine embryos [21]. Further, the impact of nutrition, climate, and embryonic mortality on ART, and the impact of ART in the developing world were studied and reviewed. For example, special efforts were made to understand the role of nutrition and management in beef cattle embryo production [22]. Information on embryonic mortality [23–26] and manipulation-induced changes in embryos [27–29] were provided. The role of uterine inflammation on embryo growth was examined in a creative way [30]. The difference in resistance to heat shock between Bos taurus and Bos
indicus was characterized [31]. The economic impact of embryo transfer in the developing world [32] has been discussed. Undoubtedly, further developments in the area of bovine embryos will be the impetus for additional reviews to document growth in knowledge in this area. Recently, we suggested defining and adopting terms used in bovine reproduction that are clear, precise and understandable, and available in a single source, to make the exchange of clinical and research information and outcomes more effective, safe and economical [33]. As part of a proposed series of reviews, the earlier report defined healthy and diseased conditions of the bovine ovary, primarily during the estrous cycle [33]. The present review will focus on terms and current understanding of the processes involved in bovine embryos prior to attachment. A supplemental review on the post-attachment bovine embryo is planned. 2. Embryonic period The term embryo describes the products of fertilization until major organogenesis is completed. In cattle, the period of the embryo extends to 42– 45 d of pregnancy [4,5,34,35]. These reports laid the foundation for terms applied to bovine embryos and defined them based on in vivo development. The headings for discussion are fertilization, timing discrepancies between in vivo and in vitro procedures, period of pre-attachment, developmental processes, and attachment. 2.1. Fertilization Fertilization refers to the union of male and female gametes to form a zygote, a process that begins with the entry of a spermatozoon into a secondary oocyte. It is completed when the nuclear envelopes of the male and female pronuclei break down and the chromatin condenses into chromosomes which are oriented on a common mitotic spindle. As in other mammals, in cattle there is close apposition of pronuclei, followed by pronuclear membrane breakdown without fusion [36]. Hence the use of the term syngamy to describe the process of fertilization in cattle is discouraged. Although the term ‘conception’ is used in the place of fertilization, the latter is the preferred term. This leads to the next issue, the term ‘fertilization rate’. It refers to the percentage of oocytes fertilized, a term that can be difficult to apply in in vivo situations, except in superstimulation regimens that result in multiple embryos. It has application in in vitro situations and is a measure of two traits, i.e., it can mean either how
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quickly fertilization occurs or the percentage of oocytes fertilized. However, it generally refers to the latter trait. Apart from superstimulation regimens in in vivo situations (number of embryos harvested), use for this term for in vivo situation is limited in cattle. In some areas ‘conception rate’ and non-return rate are used interchangeably, however, these two are not synonymous, since inevitably some cattle which were not serviced were not pregnant [37]. Since ‘fertilization’ is preferred over ‘conception’, fertilization rate can be used instead of conception rate. However, it should be mentioned that fertilization rate and pregnancy rate have distinct meanings; fertilization rate relates and indirectly attests to the quality of oocyte or spermatozoa, which enables the process of fertilization to be successfully completed. Pregnancy rate relates to the quality of the ensuing embryo. Since pregnancy is diagnosable in cattle (which also accounts for fertilization rate) the term pregnancy rate is preferred to fertilization rate. The term conceptus is similar to the word conception and refers to all the products of conception, including embryo, fetus, fetal membranes, and their contents [34]. As discussed, the use of the term conception has limited application, which is also applicable to the term conceptus. It gets further complicated since the term conceptus refers to many structures. Therefore, we suggest that the products of fertilization (embryo, fetus, fetal membranes and their contents) should be designated separately with their proper names, although the all-encompassing term conceptus can be appropriate. 2.2. Timing discrepancies between in vivo and in vitro procedures The advent of in vitro production of embryos generated challenges and inconsistencies regarding the timing of events in the process of development. Important issues are divergence in calculation of Day 0 and discrepancies in the time at which milestones in embryonic development are reached. The latter discrepancy is due to production of heterogeneous cohorts of embryos and inherent differences in embryonic micro-environment. Consequently, these factors influence developmental kinetics of embryos, leading to unsynchronized cell divisions among individual embryos; this accounts for, at least in part, the wide range in timing regarding developmental processes of cattle embryos (see section 2.4.). 2.3. Period of pre-attachment The period before attachment is correctly referred to as the pre-attachment stage [8]. The focus of this re-
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view is on events prior to the beginning of attachment or the period prior to the initiation of the process of attachment. It will be referred to as the early embryonic period, a term that gave rise to the origin of the term ‘early embryonic death’ used widely to describe the process of embryonic loss or mortality during this period [38,39]. The fate of the dead early embryo is not known, whether it is absorbed by the endometrium or expelled vaginally has been speculated but not clearly demonstrated. However, the latter phenomenon was observed in the case of post-attachment embryos [40]. In this context, use of the terms embryo reabsorption or resorption is discouraged, since it may not be the process that is actually taking place (American College of Theriogenologists listserv communication). The stage of the early embryo is very important from two perspectives. The first of these is ‘maternal recognition of pregnancy,’ a crucial step in the successful establishment of pregnancy. The discussion on this topic is beyond the scope of this review and has already been reviewed [29,41– 43]. The second issue is that this period is critical and important from the perspective of embryo manipulation. Not much is known about the growth of twin embryos during this period, since such studies have been conducted after 25–28 d post insemination [44,45]. 2.4. Developmental processes The early embryonic period includes the following developmental processes: cleavage, compaction, blastulation, expansion, hatching, and elongation (Fig. 1). Successful completion of these sequential events is important for establishment of pregnancy. Rather than defining different stages during the preattachment period [7], we will consider various processes involved in this period and recognize the timing at which the developmental stage was found. Existing knowledge in the pre-attachment period of embryo is based on observation of embryos collected from the oviduct and/or uterus or embryos that are derived from in vitro studies. The staging of the timing of various events may not be accurate, since observations usually are not from the same animal. There has been relatively little concerted study on the developing embryo (and fetus), partly because in vivo studies are difficult and expensive [46]. Observations and measurements require surgical intervention or post mortem recovery of material [46]. These approaches disrupt and interrupt the very processes under scrutiny [46]. Few studies lend themselves to non-invasive, non-terminal, or sequential methods [46]. Although in vitro studies have
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D 12
D 7.5-11
D 7-8
D6
D5
Ovary
Fertilization Cleavage Compaction Expansion Blastulation
Hatching
Oviduct Elongation
Uterus
Fig. 1. Terms and concepts regarding bovine embryos during the pre-attachment period.
provided more information in this area, it is noteworthy that there were differences in the growth pattern of embryo(s) from superstimulated and non-superstimulated cattle [47]. In addition, differences in the growth rate between in vivo and in vitro grown embryos can be ascribed to the ‘quiet embryo hypothesis’ [17,48,49]. According to this hypothesis, viable pre-attachment embryos operate at metabolite or nutrient turnover rates distributed within lower ranges than those of their less viable counterparts. Cleavage refers to the process of cell division that occurs in a fertilized oocyte in the oviduct as it moves toward the uterus [50]. These cell divisions result in successively smaller cells. After cell divisions are completed, the cells of the embryo changes
from a spherical to a polygonal shape, during a process called compaction, which occurs at approximately Day 5 [51]. Blastulation refers to the formation of a cavity eventually leading to the expansion of the embryo. Blastulation is believed to occur at ⬃Day 6 [52]. However, blastulation does not occur until Day 7 in non-superstimulated cows and half a day earlier in superstimulated cows. Expansion refers to an increase in diameter, resulting in thinning of the zona pellucida, which begins around Days 7– 8. Hatching follows expansion, which is highly variable (Days 7.5–11) [53]. This is followed by the process of elongation that starts at approximately Day 12 and ends at approximately Day 18 [50,54,55]. The days given for the above processes
Table 1 Summary of terms in pre-attachment bovine embryos. Day 0 Fertilization Fertilization rate Attachment Period of pre-attachment Early embryo Early embryonic death Cleavage Compaction Blastulation Expansion Hatching Elongation
Day of insemination or breeding or onset of estrus This term is preferred to the term conception Pregnancy rate will replace this term for an in vivo situation Attachment will replace the term implantation From Days 0 to 16 [56] Corresponds to the period before attachment Death of the embryo during the period prior to attachment Process of cell division occurring in the zygote through the 16 cell-stage [57] Change of embryo cells from spherical to polygonal Formation of a cavity within the embryo Increases in the diameter of the embryo resulting in thinning of the zona pellucida [58] Release from the zona pellucida—timing is highly variable [53] Embryo reaches approximately 12 mm [59]
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are only approximations, since Day 0 was not uniform in these studies and may not be accurate since embryos were observed from different animals or in different in vitro conditions. Table 1 has the summary of terms. 2.5. Attachment Among the events that occur during the embryonic period, the most critical and culminating event leading to a successful pregnancy is ‘implantation’. The term implantation refers to the process by which the embryo implants or inserts itself to the endometrium. The term attachment is preferred to the term implantation, since there is no penetration or insertion of the bovine embryo into the endometrium [35] as occurs in rodents and primates. Partly, this confusion arose with borrowing terminology used in mouse embryology (mice have a distinctly different window of development compared to cattle; however, pre-hatching development in cattle is comparable to mice pre-implantation development). In cattle, the term ‘attachment’ aptly describes the processes, since only fetal membranes are getting ‘attached’ to the endometrium with the embryo located within the fetal membranes [4,5,60,61]. In support of this argument, the classical work by Chang [3] suggested that the real attachment (the intricate tissue connection between the cotyledons and caruncles) is established between 40 –50 d of pregnancy. The reason for such a range for the timing of attachment is understandable since the study used abbatoir-derived materials. Further, defining the day of ovulation (Day 0) as determined by the presence of a dark-red colored, medium sized CL in one of the ovaries could have resulted in this wide range. It was also reported [60] that the chorio-allantoic membrane attaches to the endometrium between 30 and 35 d after ovulation (confirmed by transrectal palpation). Although the time at which the attachment process is completed is somewhat known, the time this process begins is not clear. It was suggested that the process of attachment begins around Day 16 [56]; this was supported by ultrastructural studies [62]. Discussions regarding placentation are beyond the scope of this work and will be included in another review. 3. Summary We propose that nomenclature be updated and revised for events associated with bovine reproduction, as suggested in human reproductive medicine
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[63,64]. As the second of a series of reviews, this mini-review is focused on defining the developmental stages in a bovine pre-attachment embryo and appropriate terminology. In this process, we suggested revising certain terminology and deleting other terms. The latter terms are syngamy, conception, implantation, and embryo resorption. It is expected that this review will make the exchange of information and outcomes more effective and economical. Further reviews will define and describe the processes of a post-attachment embryo and certain aspects of bovine pregnancy, from the perspective of scientists working with cattle. Acknowledgments The authors gratefully acknowledge the valuable assistance provided by Don Bergfeldt in reviewing and contributing to this review. References [1] Winters LM, Green WW, Comstock RE. Prenatal development of the bovine. Minn Agr Exp Sta Tech Bull 1942;151:1–50. [2] Hamilton WJ, Laing JA. Development of the egg of the cow up to the stage of blastocyst formation. J Anat 1946;80:194 –204. [3] Chang MC. Development of bovine blastocyst with a note on implantation. Anat Rec 1952;113:143– 61. [4] Marion GB, Gier HT. The process of placentation in the bovine. J Anim Sci 1958;17:1216 –17 (Abstr.). [5] Greenstein JS, Foley RC. Early embryology of the cow. J Dairy Sci 1958;41:409 –21. [6] Massip A, Mulnard P, Vanderzwalmen P, Hanzen C, Ectors F. The behaviour of cow blastocyst in vitro: cinematographic and morphometric analysis. J Anat 1982;134:399 – 405. [7] Lindner GM, Wright RW Jr. Bovine embryo morphology and evaluation. Theriogenology 1983;20:407–16. [8] Betteridge KJ, Fléchon J-E. The anatomy and physiology of pre-attachment bovine embryos. Theriogenology 1988;29: 155– 87. [9] Barros CM, Nogueira MF. Embryo transfer in Bos indicus cattle. Theriogenology 2001;56:1483–96. [10] Hasler JF. The current status and future of commercial embryo transfer in cattle. Anim Reprod Sci 2003;79:245– 64. [11] Greve T, Callesen H. Embryo technology: implications for fertility in cattle. Rev Sci Tech 2005;24:405–12. [12] Lonergan P. State-of-the-art embryo technologies in cattle. Soc Reprod Fertil Suppl 2007;64:315–25. [13] Moore K, Thatcher WW. Major advances associated with reproduction in dairy cattle. J Dairy Sci 2006;89:1254 – 66. [14] Seidel GE Jr. Superovulation and embryo transfer in cattle. Science 1981;211:351– 8. [15] Mapletoft RJ, Hasler JF. Assisted reproductive technologies in cattle: a review. Rev Sci Tech 2005;24:393– 403. [16] Thompson JG, Partridge RJ, Houghton FD, Cox CI, Leese HJ. Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos. J Reprod Fertil 1996;106:299 –306.
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J. Peippo et al. / Theriogenology 76 (2011) 1373–1379
[17] Baumann CG, Morris DG, Sreenan JM, Leese HJ. The quiet embryo hypothesis: molecular characteristics favoring viability. Mol Reprod Dev 2007;74:1345–53. [18] Givens MD, Marley SD. Approaches to biosecurity in bovine embryo transfer programs. Theriogenology 2008; 69:129 –36. [19] Sutmoller P, Wrathall AE. The risks of disease transmission by embryo transfer in cattle. Rev Sci Tech 1997;16:226 –39. [20] Van Soom A, Wrathall AE, Herrler A, Nauwynck HJ. Is the zona pellucida an efficient barrier to viral infection? Reprod Fertil Devel 2010;22:21–31. [21] Wrathall AE, Simmons HA, Van Soom A. Evaluation of risks of viral transmission to recipients of bovine embryos arising from fertilisation with virus-infected semen. Theriogenology 2006;65:247–74. [22] Jones AL, Lamb GC. Nutrition, synchronization, and management of beef embryo transfer recipients. Theriogenology 2008; 69:107–15. [23] Wathes DC. Embryonic mortality and the uterine environment. J Endocrinol 1992;134:321–5. [24] García-Ispierto I, López-Gatius F, Santolaria P, Yániz JL, Nogareda C, López-Béjar M, De Rensis F. Relationship between heat stress during the peri-implantation period and early fetal loss in dairy cattle. Theriogenology 2006;65:799 – 807. [25] Diskin MG, Morris DG. Embryonic and early foetal losses in cattle and other ruminants. Reprod Domest Anim 2008;43: 260 –7. [26] Alexopoulos NI, Maddox-Hyttel P, Tveden-Nyborg P, D’Cruz NT, Tecirlioglu TR, Cooney MA, Schauser K, Holland MK, French AJ. Developmental disparity between in vitro-produced and somatic cell nuclear transfer bovine days 14 and 21 embryos: implications for embryonic loss. Reproduction 2008;136: 433– 45. [27] Young LE, Sinclair KD, Wilmut I. Large offspring syndrome in cattle and sheep. Rev Reprod 1988;3:155– 63. [28] Lazzari G, Wrenzycki C, Herrmann D, Duchi R, Kruip T, Niemann H, Galli C. Cellular and Molecular deviations in bovine in vitro-produced embryos are related to the large offspring syndrome. Biol Reprod 2002;67:767–75. [29] Farin CE, Farmer WT, Farin PW. Pregnancy recognition and abnormal offspring syndrome in cattle. Reprod Fertil Dev 2010; 22:75– 87. [30] Hill J, Gilbert R. Reduced quality of bovine embryos cultured in media conditioned by exposure to an inflamed endometrium. Aust Vet J 2008;86:312– 6. [31] Hansen PJ. To be or not to be— determinants of embryonic survival following heat shock. Theriogenology 2007;68 Suppl 1:S40 – 8. [32] Madan ML. Animal biotechnology: applications and economic implications in developing countries. Rev Sci Tech 2005;1:127–39. [33] Peter AT, Levine H, Drost M, Bergfeldt DR. Compilation of classical and contemporary terminology used to describe morphological aspects of ovarian dynamics in cattle. Theriogenology 2009;71:1343–57. [34] Committee on bovine reproductive nomenclature. Recommendations for standardizing bovine reproductive terms. Cornell Vet 1972;62:216 –36. [35] Roberts SJ. Gestation period: embryology, fetal membranes and placenta. In: Roberts SJ, editor. Veterinary Obstetrics and Genital Diseases (Theriogenology). Ann Arbor: Edward Brothers, 1986, pp. 38 –50.
[36] Longo FJ. Fertilization: a comparative ultrastructural review. Biol Reprod 1973;9:149 –215. [37] Bartlett DE. Theriogenology: From concept to actuality. Theriogenology 1985;2:131– 45. [38] Dunne LD, Diskin MG, Sreenan JM. Embryo and foetal loss in beef heifers between day 14 of gestation and full term. Anim Reprod Sci 2000;58:39 – 44. [39] Berg DK, van Leeuwen J, Beaumont S, Berg M, Pfeffer PL. Embryo loss in cattle between days 7 and 16 of pregnancy. Theriogenology 2010;73:250 – 60. [40] Kastelic JP, Ginther OJ. Fate of conceptus and corpus luteum after induced embryonic loss in heifers. J Am Vet Med Assoc 1989;194:922–28. [41] Thatcher WW, Meyer MD, Danet-Desnoyers G, Maternal recognition of pregnancy. J Reprod Fertil Suppl 1995;49:15–28. [42] Demmers KJ, Derecka K, Flint A. Trophoblast interferon and pregnancy. Reproduction. 2001;121:41–9. [43] Wolf E, Arnold GJ, Bauersachs S, Beier HM, Blum H, Einspanier R, Fröhlich T, Herrler A, Hiendleder S, Kölle S, Prelle K, Reichenbach HD, Stojkovic M, Wenigerkind H, Sinowatz F. Embryo-maternal communication in bovine—strategies for deciphering a complex cross-talk. Reprod Domest Anim 2003;38: 276 – 89. [44] Silva-del-Río N, Colloton JD, Fricke PM. Factors affecting pregnancy loss for single and twin pregnancies in a high-producing dairy herd. Theriogenology 2009;71:1462–71. [45] López-Gatius F, García-Ispierto I, Hunter RH. Factors affecting spontaneous reduction of corpora lutea and twin embryos during the late embryonic/early fetal period in multiple ovulating dairy cows. Theriogenology 2010;73:293–9. [46] Dziuk PJ. Embryonic development and fetal growth. Anim Reproduction Science 1992;28:299 –308. [47] Sartori R, Bastos MR, Wiltbank MC. Factors affecting fertilisation and early embryo quality in single- and superovulated dairy cattle. Reprod Fertil Dev 2010; 22:151– 8. [48] Leese HJ. Quiet please, do not disturb: a hypothesis of embryo metabolism and viability. Bioessays 2002;24:845–9. [49] Leese HJ, Baumann CG, Brison DR, McEvoy TG, Sturmey RG. Metabolism of the viable mammalian embryo: quietness revisited. Mol Hum Reprod 2008;12:667–72. [50] Imakawa K, Chang KT, Christenson RK. Pre-implantation conceptus and maternal uterine communications: molecular events leading to successful implantation. Reprod Dev 2004; 50:155– 69. [51] Van Soom A, Van Vlaenderen I, Mahmoudzadeh AR, Deluyker H, de Kruif A. Compaction rate of in vitro fertilized bovine embryos related to the interval from insemination to first cleavage. Theriogenology 1992;38:905–19. [52] Holm P, Shukri NN, Vajta G, Booth P, Bendixen C, Callesen H. Developmental kinetics of the first cell cycles of bovine in vitro produced embryos in relation to their in vitro viability and sex. Theriogenology 1998;50:1285–99. [53] Brandão DO, Maddox-Hyttel P, Løvendahl P, Rumpf R, Stringfellow D, Callesen H. Post hatching development: a novel system for extended in vitro culture of bovine embryos. Biol Reprod 2004;71:2048 –55. [54] Kastelic JP, Curran S, Pierson RA, Ginther OJ. Ultrasonic evaluation of the bovine conceptus. Theriogenology 1988; 29:39 –54. [55] Blomberg L, Hashizume K, Viebahn C. Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation. Reproduction 2008:135;181–95.
J. Peippo et al. / Theriogenology 76 (2011) 1373–1379 [56] Bertolini M, Beam SW, Shim H, Bertolini LR, Moyer AL, Famula TR and Anderson GB. Growth, development and gene expression by in vivo- and in vitro-produced Day 7 and Day 16 bovine embryos. Mol Reprod Dev 2002; 63:318 –28. [57] Ushijima H, Akiyama K, Tajima T. Classification of morphological changes based on the number of cleavage divisions in bovine embryos. J Reprod Dev 2009;55:83–7. [58] Alexopoulos NI, French AJ. The prevalence of embryonic remnants following the recovery of post-hatching bovine embryos produced in vitro or by somatic cell nuclear transfer. Anim Reprod Sci 2009;114:43–53. [59] Vejlsted M, Du Y, Vajta G, Maddox-Hyttel P. Post-hatching development of the porcine and bovine embryo – defining criteria for expected development in vivo and in vitro. Theriogenology 2006;65:153– 65.
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[60] Melton AA, Berry RO, Butler OD. The interval between the time of ovulation and attachment of the bovine embryo. J Anim Sci 1951;10:993–1005. [61] Greenstein JS, Murray RW, Foley RC. Observations on the morphogenesis and histochemistry of the bovine preattachment placenta between 16 and 33 days of gestation. Anat Rec 1958; 132:321– 41. [62] Wathes DC, Wooding FB. An electron microscopic study of implantation in the cow. Am J Anat 1980;159:285–306. [63] Farquharson RG, Jauniaux E, Exalto N. Updated and revised nomenclature for description of early pregnancy events. Hum Reprod 2005;20:3008 –11. [64] Hughes LA. Disorders of sex development: a new definition and classification. Best Pract Res Clin Endocrinol Metab 2008;22: 119 –34.