Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Patterns of conceptus development and of progesterone concentrations in maternal blood preceding spontaneous early pregnancy failure in mares

Keith J. Betteridge A C , James I. Raeside A , Rudolf O. Waelchli A , Heather L. Christie A and M. Anthony Hayes B
+ Author Affiliations
- Author Affiliations

A Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

B Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

C Corresponding author. Email: kbetter@uoguelph.ca

Reproduction, Fertility and Development 30(8) 1066-1076 https://doi.org/10.1071/RD17336
Submitted: 25 August 2017  Accepted: 1 December 2017   Published: 9 January 2018

Abstract

Sixteen cases of spontaneous pregnancy loss (11 of singletons and five of pairs of twins) are described. The losses occurred between gestation Days 13 and 25 in 12 mares being monitored almost daily by transrectal ultrasonography (for measurement of conceptus growth) and blood sampling (for determination of maternal plasma progesterone concentrations as evidence of luteolysis) in experimental studies of early pregnancy. In 10 of the 16 cases the uterus was flushed and eight conceptuses were recovered for morphological assessment. Five of the 11 losses of singletons occurred before Day 16 and, with one exception, were preceded or accompanied by luteolysis. The remaining six singleton pregnancies failed after Day 16, with two cases evidencing luteolysis beforehand. Thus, overall, 6/11 singleton losses were associated with luteolysis while 5/11 were not. The five cases of simultaneous loss or degeneration of twin conceptuses all occurred on Day 19 or 20, preceded by luteolysis in only one case. These observations suggest that while the causes of spontaneous early pregnancy failure are multifactorial, luteolysis might contribute to the problem more often than has been previously contended.

Additional keywords: embryonic death, luteolysis, maternal recognition of pregnancy, reproductive efficiency, ultrasonography.


References

Allen, W. R. (2001a). Luteal deficiency and embryo mortality in the mare. Reprod. Domest. Anim. 36, 121–131.
Luteal deficiency and embryo mortality in the mare.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mrgslarug%3D%3D&md5=8b88ec6e8f5ff9f7926da9f53b2b308bCAS |

Allen, W. R. (2001b). Fetomaternal interactions and influences during equine pregnancy. Reproduction 121, 513–527.
Fetomaternal interactions and influences during equine pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXivFKgs7c%3D&md5=69c549fdea5947718499fcd26cc2fb01CAS |

Aurich, C., Weber, J., Nagel, C., Merkl, M., Jude, R., Wostmann, S., Olleck, D., Baron, U., Olek, S., and Jansen, T. (2014). Low levels of naturally occurring regulatory T lymphocytes in blood of mares with early pregnancy loss. Reprod. Fertil. Dev. 26, 827–833.
Low levels of naturally occurring regulatory T lymphocytes in blood of mares with early pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtFynsbjK&md5=617c286bb94961e3c4d123a279f1b381CAS |

Ball, B. A. (1988). Embryonic loss in mares. Incidence, possible causes, and diagnostic considerations. Vet. Clin. North Am. Equine Pract. 4, 263–290.
Embryonic loss in mares. Incidence, possible causes, and diagnostic considerations.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1czhtVGmtg%3D%3D&md5=c499f8adbe1e79567a8d8e80e25532f2CAS |

Ball, B. A. (2011). Embryonic loss. In ‘Equine Reproduction’. 2nd edn. (Eds A. O. McKinnon, E. L. Squires, W. E. Vaala and D. D. Varner.) pp. 2327–2336. (Wiley-Blackwell: Chichester, UK.)

Bartoš, L., Bartošová, J., Pluháček, J., and Šindelářová, J. (2011). Promiscuous behavior disrupts pregnancy block in domestic horse mares. Behav. Ecol. Sociobiol. 65, 1567–1572.
Promiscuous behavior disrupts pregnancy block in domestic horse mares.Crossref | GoogleScholarGoogle Scholar |

Bergfelt, D. R., Woods, J. A., and Ginther, O. J. (1992). Role of the embryonic vesicle and progesterone in embryonic loss in mares. J. Reprod. Fertil. 95, 339–347.
Role of the embryonic vesicle and progesterone in embryonic loss in mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xlt1Crsr0%3D&md5=84f94781bd60600a44a5e00888be0994CAS |

Betteridge, K. J. (2007). Equine embryology: an inventory of unanswered questions. Theriogenology 68, S9–S21.
Equine embryology: an inventory of unanswered questions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotlaiurc%3D&md5=9a53b66bf90d7e6da0df221f76ac46d5CAS |

Betteridge, K. J., Waelchli, R. O., Christie, H. L., Raeside, J. I., Quinn, B. A., and Hayes, M. A. (2012). Relationship between the timing of prostaglandin-induced luteolysis and effects on the conceptus during early pregnancy in mares. Reprod. Fertil. Dev. 24, 411–424.
Relationship between the timing of prostaglandin-induced luteolysis and effects on the conceptus during early pregnancy in mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xjs1WqsbY%3D&md5=11dfe9c56a7652c434af6966caf80607CAS |

Betteridge, K. J., Waelchli, R. O., Raeside, J. I., Christie, H. L., Quinn, B. A., and Hayes, M. A. (2014). Changes accompanying spontaneous embryonic loss in nine mares during the first month of pregnancy. J. Equine Vet. Sci. 34, 195–197.
Changes accompanying spontaneous embryonic loss in nine mares during the first month of pregnancy.Crossref | GoogleScholarGoogle Scholar |

Bosh, K. A., Powell, D., Neibergs, J. S., Shelton, B., and Zent, W. (2009). Impact of reproductive efficiency over time and mare financial value on economic returns among Thoroughbred mares in central Kentucky. Equine Vet. J. 41, 889–894.
Impact of reproductive efficiency over time and mare financial value on economic returns among Thoroughbred mares in central Kentucky.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3c3lsFSrsQ%3D%3D&md5=65be9768561c368b19554dc2a872a6e3CAS |

Brogan, P. T., Henning, H., Stout, T. A., and deRuijter-Villani, M. (2016). Relationship between colour flow Doppler sonographic assessment of corpus luteum activity and progesterone concentrations in mares after embryo transfer. Anim. Reprod. Sci. 166, 22–27.
Relationship between colour flow Doppler sonographic assessment of corpus luteum activity and progesterone concentrations in mares after embryo transfer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XjslOrtQ%3D%3D&md5=163cb65d9bcd155ddffc561ce6b86366CAS |

Canisso, I. F., Beltaire, K. A., and Bedford-Guaus, S. (2013). Premature luteal regression in a pregnant mare and subsequent pregnancy maintenance with the use of oral altrenogest. Equine Vet. J. 45, 97–100.
Premature luteal regression in a pregnant mare and subsequent pregnancy maintenance with the use of oral altrenogest.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38vmsFGktg%3D%3D&md5=1eece5ba20a9a05312ffee81404374feCAS |

Carnevale, E. M., Ramirez, R. J., Squires, E. L., Alvarenga, M. A., Vanderwall, D. K., and McCue, P. M. (2000). Factors affecting pregnancy rates and early embryonic death after equine embryo transfer. Theriogenology 54, 965–979.
Factors affecting pregnancy rates and early embryonic death after equine embryo transfer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M%2Fot1Cisg%3D%3D&md5=3ab15d4611bd8d2d64c4e9316629f695CAS |

Chen, Y. H., and Stolla, R. (2006). Using “uterine index” to diagnose embryonic death in mares. J. Equine Vet. Sci. 26, 219–224.
Using “uterine index” to diagnose embryonic death in mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjsFyjsro%3D&md5=d70eedca1edcb882a4202b38ea808a35CAS |

Ewart, J. C. (1897). ‘A Critical Period in the Development of the Horse’. (Adam and Charles Black: London.)

Gaivão, M. M. F., Rambags, B. P. B., and Stout, T. A. E. (2014). Gastrulation and the establishment of the three germ layers in the early horse conceptus. Theriogenology 82, 354–365.
Gastrulation and the establishment of the three germ layers in the early horse conceptus.Crossref | GoogleScholarGoogle Scholar |

Ginther, O. J. (1983). Mobility of the early equine conceptus. Theriogenology 19, 603–611.
Mobility of the early equine conceptus.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvVGrsA%3D%3D&md5=76f7483d7307ae4fac7268806f78e947CAS |

Ginther, O. J. (1985). Embryonic loss in mares: nature of loss after experimental induction by ovariectomy or prostaglandin F2a. Theriogenology 24, 87–98.
Embryonic loss in mares: nature of loss after experimental induction by ovariectomy or prostaglandin F2a.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvVyhug%3D%3D&md5=78ffe74f4ebd8f580446140e4fb83cc3CAS |

Ginther, O. J. (1992). Twins. In ‘Reproductive Biology of the Mare’. 2nd edn. pp. 546–559. (Equiservices: Cross Plains, WI, USA.)

Ginther, O. J., Bergfelt, D. R., Leith, G. S., and Scraba, S. T. (1985). Embryonic loss in mares: incidence and ultrasonic morphology. Theriogenology 24, 73–86.
Embryonic loss in mares: incidence and ultrasonic morphology.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvVyhtQ%3D%3D&md5=2c8d3320bfbcbe363e276e04ca2a0e27CAS |

Hanlon, D. W., Stevenson, M., Evans, M. J., and Firth, E. C. (2012). Reproductive performance of Thoroughbred mares in the Waikato region of New Zealand: 2. Multivariable analyses and sources of variation at the mare, stallion and stud farm level. N. Z. Vet. J. 60, 335–343.
Reproductive performance of Thoroughbred mares in the Waikato region of New Zealand: 2. Multivariable analyses and sources of variation at the mare, stallion and stud farm level.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38bhsFGrsA%3D%3D&md5=5593714dc6a59db69a7d1719f37e47bbCAS |

Hayes, M. A., Quinn, B. A., Lillie, B. N., Côté, O., Bienzle, D., Waelchli, R. O., and Betteridge, K. J. (2012). Changes in various endometrial proteins during cloprostenol-induced failure of early pregnancy in mares. Anim. Reprod. 9, 723–741.

Hinrichs, K., and Watson, E. D. (1988). Clinical report: recovery of a degenerating 14-day embryo in the uterine flush of a mare 7 days after ovulation. Theriogenology 30, 349–353.
Clinical report: recovery of a degenerating 14-day embryo in the uterine flush of a mare 7 days after ovulation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvFansw%3D%3D&md5=8e1b4f30cd61c6582e20c43228aeb0eaCAS |

Hinrichs, K., Sertich, P. L., and Kenney, R. M. (1986). Use of altrenogest to prepare ovariectomized mares as embryo transfer recipients. Theriogenology 26, 455–460.
Use of altrenogest to prepare ovariectomized mares as embryo transfer recipients.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvV2ktQ%3D%3D&md5=50d4f069553cd7c91714f28cd7ec8bafCAS |

Irvine, C. H. G., Sutton, P., Turner, J. E., and Mennick, P. E. (1990). Changes in plasma progesterone concentrations from Days 17 to 42 of gestation in mares maintaining or losing pregnancy. Equine Vet. J. 22, 104–106.
Changes in plasma progesterone concentrations from Days 17 to 42 of gestation in mares maintaining or losing pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c3gtV2kug%3D%3D&md5=f395c9cbff06013dd9ee8177351ac9ffCAS |

Kastelic, J. P., Adams, G. P., and Ginther, O. J. (1987). Role of progesterone in mobility, fixation, orientation, and survival of the equine embryonic vesicle. Theriogenology 27, 655–663.
Role of progesterone in mobility, fixation, orientation, and survival of the equine embryonic vesicle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXkslWjsrY%3D&md5=bb918016ccd1deb8b27154420beb0888CAS |

Kenney, R. M. (1975). Prognostic value of endometrial biopsy in the mare. J. Reprod. Fertil. Suppl. 23, 347–348.

Klein, C. (2016). Novel equine conceptus–endometrial interactions on Day 16 of pregnancy based on RNA sequencing. Reprod. Fertil. Dev. 28, 1712–1720.
Novel equine conceptus–endometrial interactions on Day 16 of pregnancy based on RNA sequencing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhsFSlsbzE&md5=d19019afe746579c05e8eb7657d8953eCAS |

Krakowski, L., Krawczyk, C. H., Wrona, Z., Dąbrowski, R., and Jarosz, L. (2010). Levels of selected T lymphocyte subpopulations in peripheral blood of mares which experienced early embryonic death. Anim. Reprod. Sci. 120, 71–77.
Levels of selected T lymphocyte subpopulations in peripheral blood of mares which experienced early embryonic death.Crossref | GoogleScholarGoogle Scholar |

Krakowski, L., Krawczyk, C. H., Kostro, K., Stefaniak, T., Novotny, F., and Obara, J. (2011). Serum levels of acute phase proteins: SAA, Hp, and progesterone (P4) in mares with early embryonic death. Reprod. Domest. Anim. 46, 624–629.
Serum levels of acute phase proteins: SAA, Hp, and progesterone (P4) in mares with early embryonic death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtV2hsL%2FI&md5=36643234986c34e2220c9a1cdf1f1bf5CAS |

Langlois, B., Blouin, C., and Chaffaux, S. (2012). Analysis of several factors of variation of gestation loss in breeding mares. Animal 6, 1925–1930.
Analysis of several factors of variation of gestation loss in breeding mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3s%2FitVCksQ%3D%3D&md5=b30a0fae0f93447799c6fff6f7a896e2CAS |

Lear, T. L., Lundquist, J., Zent, W. W., Fishback, W. D., and Clark, A. (2008). Three autosomal chromosome translocations associated with repeated early embryonic loss (REEL) in the domestic horse (Equus caballus). Cytogenet. Genome Res. 120, 117–122.
Three autosomal chromosome translocations associated with repeated early embryonic loss (REEL) in the domestic horse (Equus caballus).Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1czgs1yksA%3D%3D&md5=b5aaaf2b232d6db87616e798f6b1ac6dCAS |

Leisinger, C. A., Davolli, G. M., Foster, B. A., Whisnant, S., Paccomonti, D. L., and Pinto, C. R. F. (2016). In vivo embryo production during induced aluteal cycles in the mare. Clin. Theriogenology 8, 333.

Malschitzky, E., Pimmental, A. M., Garbade, P., Jobim, M. I. M., Gregory, R. M., and Mattos, R. C. (2015). Management strategies aiming to improve horse welfare reduce embryonic death rates in mares. Reprod. Domest. Anim. 50, 632–636.
Management strategies aiming to improve horse welfare reduce embryonic death rates in mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2Mfksl2jtQ%3D%3D&md5=229ad8375c9c9fa5bfdfe836acbb8b61CAS |

Meyers, P. J., Bonnett, B. N., and McKee, S. L. (1991). Quantifying the occurrence of early embryonic mortality on three equine breeding farms. Can. Vet. J. 32, 665–672.
| 1:STN:280:DC%2BC3crpsFSrsQ%3D%3D&md5=263a61cad8961d871a910213be213eb7CAS |

Morris, L. H. A., and Allen, W. R. (2002). Reproductive efficiency of intensively managed Thoroughbred mares in Newmarket. Equine Vet. J. 34, 51–60.
Reproductive efficiency of intensively managed Thoroughbred mares in Newmarket.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2Fptlequg%3D%3D&md5=93f3fdf6cacfa401d93f1026d2998a9bCAS |

Nath, L. C., Anderson, G. A., and Mckinnon, A. O. (2010). Reproductive efficiency of Thoroughbred and Standardbred horses in north-east Victoria. Aust. Vet. J. 88, 169–175.
Reproductive efficiency of Thoroughbred and Standardbred horses in north-east Victoria.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3cvmsFahsQ%3D%3D&md5=428b9d089252757e10e0e0490d8a7f9eCAS |

Newcombe, J. R., and Cuervo-Arango, J. (2011). The effect of time of insemination with fresh cooled transported semen and natural mating relative to ovulation on pregnancy and embryo loss rates in the mare. Reprod. Domest. Anim. 46, 678–681.
The effect of time of insemination with fresh cooled transported semen and natural mating relative to ovulation on pregnancy and embryo loss rates in the mare.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3MjotFOjtg%3D%3D&md5=67f36998cdc3d5d5789c082270a42d70CAS |

Pinna, A., Martins, G., Souza, G., and Lilenbaum, W. (2013). Influence of seroreactivity to Leptospira and reproductive failures in recipient mares of equine embryo transfer programmes. Reprod. Domest. Anim. 48, e55–e57.
Influence of seroreactivity to Leptospira and reproductive failures in recipient mares of equine embryo transfer programmes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3srkslOgtA%3D%3D&md5=7770ae8986454253d1ac80a0d3f51d5dCAS |

Quinn, B. A., Hayes, M. A., Waelchli, R. O., Kennedy, M. W., and Betteridge, K. J. (2007). Changes in major proteins in the embryonic capsule during immobilization (fixation) of the conceptus in the third week of pregnancy in the mare. Reproduction 134, 161–170.
Changes in major proteins in the embryonic capsule during immobilization (fixation) of the conceptus in the third week of pregnancy in the mare.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpvFGisL4%3D&md5=c565239159514cb186d289510b8fc0ecCAS |

Raeside, J. I., Christie, H. L., Renaud, R. L., Waelchli, R. O., and Betteridge, K. J. (2004). Estrogen metabolism in the equine conceptus and endometrium during early pregnancy in relation to estrogen concentrations in yolk-sac fluid. Biol. Reprod. 71, 1120–1127.
Estrogen metabolism in the equine conceptus and endometrium during early pregnancy in relation to estrogen concentrations in yolk-sac fluid.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnvVGqt7s%3D&md5=3f05e19e57cc462d7180612aeb47590fCAS |

Short, R. V. (1969) Implantation and the maternal recognition of pregnancy. In ‘Ciba Foundation Symposium – Foetal Autonomy’. (Eds G. E. W. Wolstenholme and M. O’Connor.) pp. 2–31. (John Wiley & Sons, Ltd.: Chichester, UK.)

Swegen, A., Grupen, C. G., Gibb, Z., Baker, M. A., de Ruijter-Villani, M., Smith, N. D., Stout, T. A. E., and Aitken, R. J. (2017). From peptide masses to pregnancy maintenance: a comprehensive proteomic analysis of the early equine embryo secretome, blastocoel fluid and capsule. Proteomics 17, .
From peptide masses to pregnancy maintenance: a comprehensive proteomic analysis of the early equine embryo secretome, blastocoel fluid and capsule.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhsFCksb%2FL&md5=ea4cf4fceac8feb37e37d5d48dba89a6CAS |

Vanderwall, D. K. (2008). Early embryonic loss in the mare. J. Equine Vet. Sci. 28, 691–702.
Early embryonic loss in the mare.Crossref | GoogleScholarGoogle Scholar |

Vanderwall, D. K. (2011). Early embryonic loss. In ‘Equine Reproduction’. 2nd edn. (Eds A. O. McKinnon, E. L. Squires, W. E. Vaala and D. D. Varner.) pp. 2118–2122. (Wiley-Blackwell: Chichester, UK.)

Vanderwall, D. K., Squires, E. L., Brinsko, S. P., and McCue, P. M. (2000). Diagnosis and management of abnormal embryonic development characterized by formation of an embryonic vesicle without an embryo in mares. J. Am. Vet. Med. Assoc. 217, 58–63.
Diagnosis and management of abnormal embryonic development characterized by formation of an embryonic vesicle without an embryo in mares.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3cvjs12qsg%3D%3D&md5=564f94a4173c7494de6048c79f43d81dCAS |

Waelchli, R. O., and Betteridge, K. J. (2013). Morphology of twin and triplet equine conceptuses during Weeks 3 and 4 of pregnancy. Reprod. Fertil. Dev. 25, 762–774.
Morphology of twin and triplet equine conceptuses during Weeks 3 and 4 of pregnancy.Crossref | GoogleScholarGoogle Scholar |

Willmann, C., Schuler, G., Hoffmann, B., Parvizi, N., and Aurich, C. (2011a). Effects of age and altrenogest treatment on conceptus development and secretion of LH, progesterone and eCG in early pregnant mares. Theriogenology 75, 421–428.
Effects of age and altrenogest treatment on conceptus development and secretion of LH, progesterone and eCG in early pregnant mares.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjs1KntA%3D%3D&md5=a244b6551e8639270bcb84c100e79340CAS |

Willmann, C., Budik, S., Walter, I., and Aurich, C. (2011b). Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus. Theriogenology 76, 61–73.
Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXntFKiurw%3D&md5=b025c3a1a41b67ea36e959b179166c6cCAS |

Wilsher, S., Lefranc, A.-C., and Allen, W. R. (2012). The effects of an advanced uterine environment on embryonic survival in the mare. Equine Vet. J. 44, 432–439.
The effects of an advanced uterine environment on embryonic survival in the mare.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC38zmtVGksA%3D%3D&md5=ee2dd546cf9a12b0cbb6829f6f2abde6CAS |

Yang, Y.-J., and Cho, G.-J. (2007). Factors concerning embryonic death in Thoroughbred mares in South Korea. J. Vet. Med. Sci. 69, 787–792.
Factors concerning embryonic death in Thoroughbred mares in South Korea.Crossref | GoogleScholarGoogle Scholar |