Revisiting oocyte-somatic cell interactions: in search of novel intrafollicular predictors and regulators of oocyte developmental competence

Abstract

Prediction and improvement of oocyte competence are two critical issues in assisted reproductive technology to improve infertility therapy. The lack of reliable and objective predictors of oocyte developmental competence for oocyte/embryo selection during in vitro fertilization hampers the effectiveness of this technology. Likewise, the low pregnancy rate resulting from in vitro maturation of human oocytes represents a major obstacle for its clinical application. Oocyte competence is progressively acquired during follicular development, and the oocyte plays a dominant role in regulating granulosa cell functions and maintaining the microenvironment appropriate for the development of its competence. Hence, granulosa cell functions are reflective of oocyte competence, and molecular markers of granulosa cells are potentially reliable predictors of oocyte quality. With the advent of the functional genomics era, the transcriptome of granulosa cells has been extensively characterized. Experimental data supporting granulosa cell markers as predictors of oocyte competence are now emerging in both animal models and humans. Future efforts should focus on integrating granulosa cell genetic markers as parameters for oocyte/embryo selection. Moreover, novel in vitro evidence highlights the effectiveness of exogenous oocyte-secreted factors in promoting oocyte developmental competence in animal models. The challenge in evaluating the effect of oocyte-secreted factors on oocyte quality in a clinical setting is to standardize the various preparations of these recombinant proteins and decipher their complex interactions/cooperativity within the germline-somatic cell regulatory loop.

Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles

“…The acquisition of quality oocyte and consequently quality embryo during folliculogenesis relies on bidirectional communication between oocyte and its surrounding cumulus cells (CC) [14,15]. This means that CC gene expression pattern is an indirect marker of oocytes' state [16].…”

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

“…The ability to achieve such development, known as oocyte competence, is acquired mainly during the antral phase of folliculogenesis through wellcoordinated molecular processes, including proper nuclear maturation and final cytoplasmic maturation (Sirard et al 2003, Krisher 2004, Kimura et al 2007. Successful oocyte final maturation is therefore a complex process that implies many factors such as intrinsic oocyte quality (Lonergan et al 2003, Wang & Sun 2007, dialog with neighboring somatic compartment (Matzuk et al 2002, Tanghe et al 2002, Yokoo & Sato 2004, Gilchrist et al 2008, Li et al 2008, and functional gap junctions (Thomas et al 2004, Lodde et al 2007. It has been established that, inside the follicle, the oocyte is surrounded by granulosa cell (GC) populations that, through folliculogenesis, differentiate into both mural GCs and cumulus cells (CCs).…”

Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality

“…Evaluation of cumulus or granulosa cells to identify additional factors associated with oocyte/embryo quality and positive IVF outcomes has been performed [49,50]. For example, large-scale microarray analyses have identified a correlations between ferridoxin (FDX1), aromatase (CYP19A1), and CDC42 levels in follicular cells and oocyte competence [51], and between BCL2L11, PCK1 and NFIB levels in cumulus cells and embryo potential and the likelihood of a successful pregnancy [52].…”