Effect of reproductive tract environment following controlled ovarian hyperstimulation treatment on embryo development and global transcriptome profile of blastocysts: implications for animal breeding and human assisted reproduction

Abstract

background: In mammals, the reproductive tract plays a crucial role in the success of early reproductive events and provides an optimal microenvironment for early embryonic development. However, changes in the reproductive tract environment associated with controlled ovarian hyperstimulation and the influence on the embryo transcriptome profile have not been investigated. Therefore, we investigated differences in the development rate and the transcriptome profile of bovine blastocysts developing in the reproductive tract of unstimulated or superovulated heifers.methods: Nineteen Simmental heifers were synchronized, superovulated and artificially inseminated; nine heifers were flushed on Day 2 after insemination and 2-4-cell stage embryos were recovered and endoscopicaly transferred to the ipsilateral oviduct of unstimulated (i.e. single-ovulating) synchronized recipients (n ¼ 4 recipients; 25 -50 embryos per recipient). The remaining 10 superovulated heifers and the unstimulated recipients were then non-surgically flushed on Day 7 to collect embryos. The blastocyst transcriptome profile was examined using the Affymetrix GeneChip Bovine Genome Array.results: The proportion of embryos, which developed to the blastocyst stage, was lower in superovulated heifers than unstimulated heifers (P , 0.05). Blastocysts that developed under the abnormal endocrine conditions associated with ovulation induction showed higher cellular and metabolic activities, as genes involved in the oxidative phosphorylation pathway, different metabolic processes and translation and transcription processes, in addition to genes expressed in response to stress, were highly expressed compared with embryos that developed in the oviduct of unstimulated animals. conclusions:The environment in which the embryo develops in the oviduct/uterus significantly alters gene expression patterns, especially those genes that regulate metabolic activity in the embryo.

Oviductal secretion and gamete interaction

“…It has been reported that the condition of the oviduct where bovine embryos were placed until reaching the blastocyst stage influenced their gene expression patterns, especially for those genes that regulate metabolic activity (Gad et al 2011). Thus, factors from the oviductal secretion could affect the embryo gene expression.…”

Mitochondrial membrane potential in 2-cell stage embryos correlates with the success of preimplantation development

“…3). The oviduct plays an important role in gamete maturation, gamete transportation, fertilization, and preimplantation development (Ellington 1991, Barriere et al 2002, Lyons et al 2006, Brussow et al 2008, Kolle et al 2010, Gad et al 2011. Therefore, some factors in the oviduct may activate embryonic mitochondria and protect them from oxidative stress (Figs 3 and 5).…”

Identification of differentially expressed genes in the oviduct of two rabbit lines divergently selected for uterine capacity using suppression subtractive hybridization

“…Taking into account the steroid inactivation role of the HSD17B4 protein, we could hypothesize that overexpression of HSD17B4 in the oviduct of L-line rabbits could modify the estrogen concentration, changing the oviduct fluid composition and subsequently affecting the early embryonic development (Murray 1993;Killian 2004;Gad et al 2011). Similarly, changes in steroid concentration could also modify the expression of PGR, causing the desynchronization of oviductal and uterine environments and affecting the posterior development and implantation of embryos (Gad et al 2011;Waclawik 2011). ERO1L gene is involved in the "oxidation-reduction process".…”