A Physiological, Rather Than a Superovulated, Post-Implantation Environment Can Attenuate the Compromising Effect of Assisted Reproductive Techniques on Gene Expression in Developing Mice Embryos

Assisted reproductive techniques (ARTs) may perturb the pre-/peri-conception microenvironments, which subsequently threaten the health of offspring. This study aimed to investigate the effects of superovulation, vitrification, in vitro culture, and embryo transfer on the expression of epigenetic modulators, imprinted genes, and pluripotency markers in expanded blastocysts and Day-9.5 (D9.5) concepti. Results revealed that 53.4% (8/15) and 86.7% (13/15) of genes in the fetus and placenta, respectively, have similar patterns of transcription in all D9.5 concepti, despite the perturbed mRNA expression observed at the blastocyst stage for each embryo-production technique. These observations indicate a counterbalancing of the abnormal expression pattern analyzed at the blastocyst stage during post-implantation development, particularly when the uterus of a naturally synchronized foster mother is employed. Superovulation resulted in the most abnormal expression patterns compared to other treatment groups, although these same blastocysts were able to develop in a synchronized uterus. Thus, superovulation creates a hormonal environment that negatively affected gene expression and impairs fetal growth more adversely during post-implantation development than other ART protocols, such as in vitro culture, vitrification, or embryo transferalthough each did contribute negatively to the implantation and development process. Together, these results may have implications for treating infertility in humans. Mol. Reprod. Dev. 82: 191-206, 2015. (c) 2015 Wiley Periodicals, Inc.