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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Low plasma progestin concentration during the early postovulatory phase impairs equine conceptus development in the late preimplantation phase

Carolina T. C. Okada https://orcid.org/0000-0002-1758-0334 A , Martim Kaps A , Dragos Scarlet B , Stephan Handschuh C , Camille Gautier https://orcid.org/0000-0002-3604-4836 B , Maria Melchert A , Joerg Aurich B and Christine Aurich https://orcid.org/0000-0001-6077-7362 A D
+ Author Affiliations
- Author Affiliations

A Platform Artificial Insemination and Embryo Transfer, Department for Small Animals and Horses, Vetmeduni Vienna, Veterinärplatz 1, 1210 Vienna, Austria.

B Section for Obstetrics, Gynaecology and Andrology, Department for Small Animals and Horses, Vetmeduni Vienna, Veterinärplatz 1, 1210 Vienna, Austria.

C VetImaging, VetCore Facility for Research, Vetmeduni Vienna, Veterinärplatz 1, 1210 Vienna, Austria.

D Corresponding author. Email: christine.aurich@vetmeduni.ac.at

Reproduction, Fertility and Development 32(13) 1156-1167 https://doi.org/10.1071/RD20116
Submitted: 27 April 2020  Accepted: 24 July 2020   Published: 18 August 2020

Abstract

In horses, low postovulatory progestin concentrations delay downregulation of endometrial progesterone receptors, impairing histotroph composition. The aim of this study was to evaluate conceptus development until placentation in mares under experimentally reduced progestin concentrations in the early postovulatory phase. Eleven mares were inseminated until ovulation and received the prostaglandin F agonist cloprostenol (125 µg) once daily for 4 days after ovulation (treatment) or were left untreated (control). Conceptus growth and development was analysed daily from Day 10 after ovulation by ultrasound. On Day 34 conceptuses were recovered and underwent microcomputed tomography. Statistical comparison was performed by non-parametric Wilcoxon test or Chi2. First visualisation of embryonic vesicle, embryo proper and heartbeat did not differ. Conceptus fixation in the uterus occurred earlier in controls than in conceptuses recovered from treatment pregnancies (P < 0.05). Embryos from treatment pregnancies were smaller (P < 0.05) and lighter (P < 0.05) than controls. In the lung, the mean number of bronchi was lower in embryos from treatment pregnancies than from control pregnancies (P < 0.05). Persistence of communication between the cardiac ventricles was observed more often in embryos from treatment than control pregnancies (P < 0.05). In conclusion, subphysiological progestin concentrations in the early postovulatory period impaired conceptus development before placentation in horses.

Graphical Abstract Image

Additional keywords: corpus luteum, embryo, horse, pregnancy, prostaglandin.


References

Acker, D. A., Curran, S., Bersu, E. T., and Ginther, O. J. (2001). Morphologic stages of the equine embryo proper on Days 17 to 40 after ovulation. Am. J. Vet. Res. 62, 1358–1364.
Morphologic stages of the equine embryo proper on Days 17 to 40 after ovulation.Crossref | GoogleScholarGoogle Scholar | 11560260PubMed |

Atkins, D. T., Harms, P. G., Sorensen, A. M., and Fleeger, J. L. (1976). Isolation, identification and quantitation of serum 5α-pregnane-3,20-dione and its relationship to progesterone in the pregnant mare. Steroids 28, 867–880.
Isolation, identification and quantitation of serum 5α-pregnane-3,20-dione and its relationship to progesterone in the pregnant mare.Crossref | GoogleScholarGoogle Scholar | 1014047PubMed |

Aurich, C., Daels, P. F., Ball, B. A., and Aurich, J. E. (1995). Effects of gonadal steroids on the opioid regulation of LH and prolactin release in ovariectomized pony mares. J. Endocrinol. 147, 195–202.
Effects of gonadal steroids on the opioid regulation of LH and prolactin release in ovariectomized pony mares.Crossref | GoogleScholarGoogle Scholar | 7490548PubMed |

Battut, I., Colchen, S., Fieni, F., Tainturier, D., and Bruyas, J. F. (1997). Success rates when attempting to nonsurgically collect equine embryos at 144, 156 or 168 hours after ovulation. Equine Vet. J. Suppl. 29, 60–62.
Success rates when attempting to nonsurgically collect equine embryos at 144, 156 or 168 hours after ovulation.Crossref | GoogleScholarGoogle Scholar |

Behrens, C., Aurich, J. E., Klug, E., Naumann, H., and Hoppen, H. O. (1993). Inhibition of gonadotrophin release in mares during the luteal phase of the oestrous cycle by endogenous opioids. J. Reprod. Fertil. 98, 509–514.
Inhibition of gonadotrophin release in mares during the luteal phase of the oestrous cycle by endogenous opioids.Crossref | GoogleScholarGoogle Scholar | 8410818PubMed |

Bergfelt, D. R., Pierson, R. A., and Ginther, O. J. (2006). Regression and resurgence of the CL following PGF2α treatment 3 days after ovulation in mares. Theriogenology 65, 1605–1619.
Regression and resurgence of the CL following PGF2α treatment 3 days after ovulation in mares.Crossref | GoogleScholarGoogle Scholar | 16242763PubMed |

Betteridge, K. J., Eaglesome, M. D., Mitchell, D., Flood, P. F., and Beriault, R. (1982). Development of horse embryos up to twenty-two days after ovulation: observations on fresh specimens. J. Anat. 135, 191–209.
| 7130052PubMed |

Betteridge, K. J., Waelchli, R. O., Christie, H. L., Raeside, J. I., Quinn, B. A., and Hayes, 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 | 22401273PubMed |

Beyer, T., Rink, B. E., Scarlet, D., Walter, I., Kunert, S., and Aurich, C. (2019). Early luteal phase progestin concentration influences endometrial function in pregnant mares. Theriogenology 125, 236–241.
Early luteal phase progestin concentration influences endometrial function in pregnant mares.Crossref | GoogleScholarGoogle Scholar | 30476756PubMed |

Clemente, M., De La Fuente, J., Fair, T., Al Naib, A., Gutierrez-Adan, A., Roche, J. F., Rizos, D., and Lonergan, P. (2009). Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium? Reproduction 138, 507–517.
Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium?Crossref | GoogleScholarGoogle Scholar | 19556439PubMed |

Ermakova, O., Orsini, T., Gambadoro, A., Chiani, F., and Tocchini-Valentini, G. P. (2018). Three-dimensional microCT imaging of murine embryonic development from immediate post-implantation to organogenesis: application for phenotyping analysis of early embryonic lethality in mutant animals. Mamm. Genome 29, 245–259.
Three-dimensional microCT imaging of murine embryonic development from immediate post-implantation to organogenesis: application for phenotyping analysis of early embryonic lethality in mutant animals.Crossref | GoogleScholarGoogle Scholar | 29170794PubMed |

Esteller-Vico, A., Macleod, J. N., Graugnard, D. E., Scoggin, K. E., Squires, E. L., Troedsson, M. H., and Ball, B. A. (2016). 252 Effects of low circulating progesterone concentration during early diestrus on the endometrial transcriptome of the mare. Reprod. Fertil. Dev. 28, 258.
252 Effects of low circulating progesterone concentration during early diestrus on the endometrial transcriptome of the mare.Crossref | GoogleScholarGoogle Scholar |

Forde, N., Simintiras, C. A., Sturmey, R., Mamo, S., Kelly, A. K., Spencer, T. E., Bazer, F. W., and Lonergan, P. (2014). Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle. PLoS One 9, e100010.
Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle.Crossref | GoogleScholarGoogle Scholar | 24960174PubMed |

Franciolli, A. L. R., Cordeiro, B. M., Fonseca, E. T., Rodrigues, M. N., Sarmento, C. A. P., Ambrosio, C. E., Carvalho, A. F., Miglino, M. A., and Silva, L. A. (2011). Characteristics of the equine embryo and fetus from Days 15 to 107 of pregnancy. Theriogenology 76, 819–832.
Characteristics of the equine embryo and fetus from Days 15 to 107 of pregnancy.Crossref | GoogleScholarGoogle Scholar |

Garrett, J. E., Geisert, R. D., Zavy, M. T., and Morgan, G. L. (1988). Evidence for maternal regulation of early conceptus growth and development in beef cattle. J. Reprod. Fertil. 84, 437–446.
Evidence for maternal regulation of early conceptus growth and development in beef cattle.Crossref | GoogleScholarGoogle Scholar | 3199361PubMed |

Gastal, M. O., Gastal, E. L., Kot, K., and Ginther, O. J. (1996). Factors related to the time of fixation of the conceptus in mares. Theriogenology 46, 1171–1180.
Factors related to the time of fixation of the conceptus in mares.Crossref | GoogleScholarGoogle Scholar | 16727980PubMed |

Hiraiwa, N., Ishimoto, M., and Yasue, H. (2013). Examination of the mouse embryo by micro-CT. Exp. Anim. 62, 57–61.
Examination of the mouse embryo by micro-CT.Crossref | GoogleScholarGoogle Scholar | 23357947PubMed |

Holtan, D. W., Nett, T. M., and Estergreen, V. L. (1975). Plasma progestins in pregnant, postpartum and cycling mares. J. Anim. Sci. 40, 251–260.
Plasma progestins in pregnant, postpartum and cycling mares.Crossref | GoogleScholarGoogle Scholar | 1116961PubMed |

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 | 16726270PubMed |

Kenney, R. M. (1978). Cyclic and pathologic changes of the mare endometrium as detected by biopsy, with a note on early embryonic death. J. Am. Vet. Med. Assoc. 172, 241–262.
| 621166PubMed |

Leisinger, C. A., Medina, V., Markle, M. L., Paccamonti, D. L., and Pinto, C. R. F. (2018). Morphological evaluation of Day 8 embryos developed during induced aluteal cycles in the mare. Theriogenology 105, 178–183.
Morphological evaluation of Day 8 embryos developed during induced aluteal cycles in the mare.Crossref | GoogleScholarGoogle Scholar | 28987795PubMed |

Lonergan, P. (2011). Influence of progesterone on oocyte quality and embryo development in cows. Theriogenology 76, 1594–1601.
Influence of progesterone on oocyte quality and embryo development in cows.Crossref | GoogleScholarGoogle Scholar | 21855985PubMed |

MacPherson, M. L., and Reimer, J. M. (2000). Twin reduction in the mare: current options. Anim. Reprod. Sci. 60–61, 233–244.
Twin reduction in the mare: current options.Crossref | GoogleScholarGoogle Scholar | 10844198PubMed |

Mann, G. E., Fray, M. D., and Lamming, G. E. (2006). Effects of time of progesterone supplementation on embryo development and interferon-s production in the cow. Vet. J. 171, 500–503.
Effects of time of progesterone supplementation on embryo development and interferon-s production in the cow.Crossref | GoogleScholarGoogle Scholar | 16624716PubMed |

Matsuda, Y., Ono, S., Otake, Y., Handa, S., Kose, K., Haishi, T., Yamada, S., Uwabe, C., and Shiota, K. (2007). Imaging of a large collection of human embryo using a super-parallel MR microscope. Magn. Reson. Med. Sci. 6, 139–146.
Imaging of a large collection of human embryo using a super-parallel MR microscope.Crossref | GoogleScholarGoogle Scholar | 18037794PubMed |

Metscher, B. D. (2009). MicroCT for developmental biology: a versatile tool for high-contrast 3D imaging at histological resolutions. Dev. Dyn. 238, 632–640.
MicroCT for developmental biology: a versatile tool for high-contrast 3D imaging at histological resolutions.Crossref | GoogleScholarGoogle Scholar | 19235724PubMed |

Nie, G. J., Johnson, K. E., Wenzel, J. H. W., and Braden, T. D. (2003). Luteal function in mares following administration of oxytocin, cloprostenol or saline on Day 0, 1 or 2 post-ovulation. Theriogenology 60, 1119–1125.
Luteal function in mares following administration of oxytocin, cloprostenol or saline on Day 0, 1 or 2 post-ovulation.Crossref | GoogleScholarGoogle Scholar | 12935851PubMed |

Okumu, L. A., Forde, N., Fahey, A. G., Fitzpatrick, E., Roche, J. F., Crowe, M. A., and Lonergan, P. (2010). The effect of elevated progesterone and pregnancy status on mRNA expression and localisation of progesterone and oestrogen receptors in the bovine uterus. Reproduction 140, 143–153.
The effect of elevated progesterone and pregnancy status on mRNA expression and localisation of progesterone and oestrogen receptors in the bovine uterus.Crossref | GoogleScholarGoogle Scholar | 20403910PubMed |

Oriol, J. G., Sharom, F. J., and Betteridge, K. J. (1993). Developmentally regulated changes in the glycoproteins of the equine embryonic capsule. J. Reprod. Fertil. 99, 653–664.
Developmentally regulated changes in the glycoproteins of the equine embryonic capsule.Crossref | GoogleScholarGoogle Scholar | 8107051PubMed |

Rambags, B. P. B., Van Tol, H. T. A., Van Den Eng, M. M., Colenbrander, B., and Stout, T. A. E. (2008). Expression of progesterone and oestrogen receptors by early intrauterine equine conceptuses. Theriogenology 69, 366–375.
Expression of progesterone and oestrogen receptors by early intrauterine equine conceptuses.Crossref | GoogleScholarGoogle Scholar |

Rizos, D., Scully, S., Kelly, A. K., Ealy, A. D., Moros, R., Duffy, P., Al Naib, A., Forde, N., and Lonergan, P. (2012). Effects of human chorionic gonadotrophin administration on Day 5 after oestrus on corpus luteum characteristics, circulating progesterone and conceptus elongation in cattle. Reprod. Fertil. Dev. 24, 472–481.
Effects of human chorionic gonadotrophin administration on Day 5 after oestrus on corpus luteum characteristics, circulating progesterone and conceptus elongation in cattle.Crossref | GoogleScholarGoogle Scholar | 22401279PubMed |

Rodrigues, R. F., Rodrigues, M. N., Franciolli, A. L. R., Carvalho, R. C., Rigoglio, N., Jacob, J. C. F., Gastal, E. L., and Miglino, M. A. (2014). Embryonic and fetal development of the cardiorespiratory apparatus in horses (Equus caballus) from 20 to 115 days of gestation. J. Cytol. Histol. 05, 240.

Satterfield, M. C., Bazer, F. W., and Spencer, T. E. (2006). Progesterone regulation of preimplantation conceptus growth and galectin 15 (LGALS15) in the ovine uterus 1. Biol. Reprod. 75, 289–296.
Progesterone regulation of preimplantation conceptus growth and galectin 15 (LGALS15) in the ovine uterus 1.Crossref | GoogleScholarGoogle Scholar | 16707766PubMed |

Scholtz, E. L., Krishnan, S., Ball, B. A., Corbin, C. J., Moeller, B. C., Stanley, S. D., McDowell, K. J., Hughes, A. L., McDonnell, D. P., and Conley, A. J. (2014). Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesterone. Proc. Natl. Acad. Sci. USA 111, 3365–3370.
Pregnancy without progesterone in horses defines a second endogenous biopotent progesterone receptor agonist, 5α-dihydroprogesterone.Crossref | GoogleScholarGoogle Scholar | 24550466PubMed |

Si-Tayeb, K., Lemaigre, F. P., and Duncan, S. A. (2010). Organogenesis and development of the liver. Dev. Cell 18, 175–189.
Organogenesis and development of the liver.Crossref | GoogleScholarGoogle Scholar | 20159590PubMed |

Spencer, T. E., and Bazer, F. W. (2002). Biology of progesterone action during pregnancy recognition and maintenance of pregnancy. Front. Biosci. 7, 1879–1898.
Biology of progesterone action during pregnancy recognition and maintenance of pregnancy.Crossref | GoogleScholarGoogle Scholar |

Stewart, F., Kennedy, M. W., and Suire, S. A. (2000). Novel uterine lipocalin supporting pregnancy in equids. Cell. Mol. Life Sci. 57, 1373–1378.
Novel uterine lipocalin supporting pregnancy in equids.Crossref | GoogleScholarGoogle Scholar | 11078016PubMed |

Theiler, K. (1989) ‘The House Mouse Atlas of Embryonic Development’. (Springer: New York.)

Troedsson, M. H. T., Ababneh, M. M., Ohlgren, A. F., Madill, S., Vetscher, N., and Gregas, M. (2001). Effect of periovulatory prostaglandin F2alpha on pregnancy rates and luteal function in the mare. Theriogenology 55, 1891–1899.
Effect of periovulatory prostaglandin F2alpha on pregnancy rates and luteal function in the mare.Crossref | GoogleScholarGoogle Scholar |

Warburton, D., El-Hashash, A., Carraro, G., Tiozzo, C., Sala, F., Rogers, O., De Langhe, F., Kemp, P. J., Riccardi, D., Torday, J., Bellusci, S., Shi, W., Lubkin, S. R., and Jesudason, E. (2010). Lung organogenesis. Curr. Top. Dev. Biol. 90, 73–158.
Lung organogenesis.Crossref | GoogleScholarGoogle Scholar | 20691848PubMed |

Weber, J. A., Freeman, D. A., Vanderwall, D. K., and Woods, G. L. (1991). Prostaglandin E2 hastens oviductal transport of equine embryos. Biol. Reprod. 45, 544–546.
Prostaglandin E2 hastens oviductal transport of equine embryos.Crossref | GoogleScholarGoogle Scholar | 1751628PubMed |

Willmann, C., Budik, S., Walter, I., and Aurich, C. (2011a). 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 | 21396689PubMed |

Willmann, C., Schuler, G., Hoffmann, B., Parvizi, N., and Aurich, C. (2011b). 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 | 21144568PubMed |

Wilsher, S., Gower, S., and Allen, W. R. T. (2011). Immunohistochemical localisation of progesterone and oestrogen receptors at the placental interface in mares during early pregnancy. Anim. Reprod. Sci. 129, 200–208.
Immunohistochemical localisation of progesterone and oestrogen receptors at the placental interface in mares during early pregnancy.Crossref | GoogleScholarGoogle Scholar | 22176887PubMed |

Wong, M. D., Dorr, A. E., Walls, J. R., Lerch, J. P., and Henkelman, M. R. (2012). A novel 3D mouse embryo atlas based on micro-CT. Development 139, 3248–3256.
A novel 3D mouse embryo atlas based on micro-CT.Crossref | GoogleScholarGoogle Scholar | 22872090PubMed |

Yamada, S., Samtani, R. R., Lee, E. S., Lockett, E., Uwabe, C., Shiota, K., Anderson, S. A., and Lo, C. W. (2010). Developmental atlas of the early first trimester human embryo. Dev. Dyn. 239, 1585–1595.
Developmental atlas of the early first trimester human embryo.Crossref | GoogleScholarGoogle Scholar | 20503356PubMed |