Uterine influences on conceptus development in fertility-classified heifers

Authors: MORAES, JOAO - University Of Missouri; BEHURA, SUSANTA - University Of Missouri; Geary, Thomas; HANSEN, PETER - University Of Florida; NEIBERGS, HOLLY - Washington State University; SPENCER, THOMAS - University Of Missouri

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2018
Publication Date: 2/5/2018
Citation: Moraes, J.G., Behura, S.K., Geary, T.W., Hansen, P.J., Neibergs, H.L., Spencer, T.E. 2018. Uterine influences on conceptus development in fertility-classified heifers. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1721191115.

Interpretive Summary: Exact signaling between the uterus and embryo is needed for pregnancy success in all mammals. A major issue is how the uterus influences fertility in cattle. Repeated embryo transfer was used to classify cows as high fertile (HF), sub fertile (SF) and infertile (IF). To assess pregnancy loss, two embryos were transferred into HF, SF and IF cows on day 7, and pregnancy outcome assessed on day 17. Pregnancy rate was substantially higher in HF (71%) and SF (90%) than IF (20%) cows. Embryos were about twice as long in HF than SF cows. There was a major difference in gene expression of the uterus in HF and SF cows that were pregnant. Distinct gene expression differences were also observed in the embryos from HF and SF cows. This study found that errors in uterine-embryo signalling cause pregnancy loss in SF cows during embryo implantation. This research improves our understanding of the mechanisms that lead to pregnancy loss and provide a foundation for improving pregnancy success in domestic animals and humans.

Technical Abstract: A major unresolved issue is how the uterus influences infertility and subfertility in cattle. Serial embryo transfer was previously used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). To assess pregnancy loss in those animals, two in vivo produced embryos were transferred into HF, SF and IF heifers on day 7, and pregnancy outcome assessed on day 17. Pregnancy rate was substantially higher in HF (71%) and SF (90%) than IF (20%) heifers. Elongating conceptuses were about two-fold longer in HF than SF heifers. Transcriptional profiling detected relatively few differences in endometrium of nonpregnant HF, SF and IF heifers. In contrast, there was a substantial difference in the transcriptome response of the endometrium to pregnancy between HF and SF heifers. Considerable deficiencies in pregnancy-dependent biological pathways associated with extracellular matrix structure and organization as well as cell adhesion were found in endometrium of SF animals. Distinct gene expression differences were also observed in conceptuses from HF and SF animals with many of the genes decreased in SF conceptuses known to be embryonic lethal in mice due to defects in embryo and/or placental development. Analyses of biological pathways, key players, and ligand-receptor interactions based on transcriptome data divulged substantial evidence for dysregulation of conceptus-endometrial interactions in SF animals. These results support the ideas that: the uterus impacts conceptus survival and programs conceptus development; and ripple effects of dysregulated conceptus-endometrial interactions elicit loss of the post-elongation conceptus in SF cattle during the implantation period of pregnancy.