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Placenta2017; 57; 175-182; doi: 10.1016/j.placenta.2017.07.007

Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes.

Abstract: Placental imprinted genes appear to be sensitive indicators of an inappropriate pre-implantation environment. This study examined the effects of negative uterine asynchrony after embryo transfer (ET) on early horse embryo development, and yolk-sac membrane expression of DNA methyltransferases (DNMTs) and equine specific placental imprinted genes. Methods: Day 8 embryos were transferred to recipient mares on day 8 (synchronous) or day 3 (asynchronous) after ovulation, and conceptuses were recovered 6 or 11 days later (day 14 or 19 of development). Results: Day 14 conceptuses recovered from an asynchronous uterus had a smaller embryonic disc, in which primitive streak development was visibly retarded compared to conceptuses from a synchronous uterus. Similarly, length, somite number and organogenesis were retarded in day 19 embryos after asynchronous ET. Maternal (GRB10, H19, IGF2R, PHLDA2) and paternal (IGF2, INSR, PEG3, PEG10, DIO3, NDN, SNRPN) imprinted genes and DNMTs (DNMT1, 3A and 3B) were all up-regulated between day 14 and 19 of pregnancy and, for most, mRNA expression was higher in synchronous than asynchronous day 19 yolk-sac membrane. Expression of the paternally imprinted gene HAT1 increased between day 14 and 19 of pregnancy, but was not affected by the asynchrony. Conclusions: Conceptus development and upregulation of DNMTs and imprinted genes were delayed rather than dysregulated after transfer into a negatively asynchronous uterus. We propose that this ability to 'reset' conceptus development to uterine stage is an adaptation that explains why horse embryos are unusually tolerant of asynchrony after ET.
Publication Date: 2017-07-11 PubMed ID: 28864009DOI: 10.1016/j.placenta.2017.07.007Google Scholar: Lookup
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  • Journal Article

Summary

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The study investigates how negative uterine asynchrony after embryo transfer affects the early development of horse embryos and the expression of certain placental imprinted genes and DNA methyltransferases. The researchers found that embryos developed in an asynchronous uterus had slower physical development and upregulation of these genes, but they are able to adapt and ‘reset’ their development to the uterine stage, highlighting the inherent resilience of horse embryos to asynchrony post-embryo transfer.

Objective and Methodology of the Study

  • The study’s main aim was to understand the impact of negative uterine asynchrony, a situation where the embryo transfer takes place prematurely (on day 3 rather than day 8 post-ovulation, in this case), on the early development of horse embryos and the expression of placental imprinted genes and DNA methyltransferases.
  • Placental imprinted genes are important as they are seemingly sensitive indicators of an unsuitable pre-implantation environment.
  • To carry out this research, the scientists transferred Day 8 embryos into recipient mares either on Day 8 (synchronous) or Day 3 (asynchronous) after ovulation. They then recovered the conceptuses 6 or 11 days later (on Day 14 or 19 of the development).

Findings of the Research

  • In the asynchronous conditions, Day 14 conceptuses had visibly smaller embryonic discs and slower developing primitive streaks compared to their synchronous counterparts.
  • Similarly, asynchronous Day 19 embryos showed retardation in length, somite number, and organogenesis compared to synchronous Day 19 embryos.
  • Various maternal and paternal imprinted genes, as well as DNA methyltransferases (DNMT1, 3A, and 3B), saw higher up-regulation (increase in response to an external stimulus) between Day 14 and Day 19 of pregnancy. This was predominantly higher in synchronous Day 19 yolk sac membrane than in its asynchronous counterpart.

Implications of the Results

  • Interestingly, the researchers also found an ability to ‘reset’ conceptus development to the uterine stage. Even though their development is initially delayed in asynchronously implanted embryos, the embryos can adjust their development process to match the stage of the uterus into which they are implanted. This adaptation might explain why horse embryos are unusually tolerant of asynchrony after an embryo transfer.

Cite This Article

APA
Gibson C, de Ruijter-Villani M, Stout TAE. (2017). Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes. Placenta, 57, 175-182. https://doi.org/10.1016/j.placenta.2017.07.007

Publication

ISSN: 1532-3102
NlmUniqueID: 8006349
Country: Netherlands
Language: English
Volume: 57
Pages: 175-182

Researcher Affiliations

Gibson, Charlotte
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: c.m.e.gibson@uu.nl.
de Ruijter-Villani, Marta
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: m.villani@uu.nl.
Stout, Tom A E
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. Electronic address: t.a.e.stout@uu.nl.

MeSH Terms

  • Animals
  • DNA Modification Methylases / metabolism
  • Embryo Transfer
  • Embryonic Development
  • Female
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting
  • Horses / embryology
  • Uterus / physiology