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.

Figure 1:

Potential intrafollicular predictors and regulators of oocyte quality within the oocyte–somatic cell regulatory loop. Oocyte-secreted factors (GDF9, BMP15, FGF8B and other unknown factors) can act on the adjacent cumulus cells via SMAD2/3, SMAD1/5/8 or other pathways to induce the expression of genes from a variety of categories (e.g. cumulus expansion-related genes Has2 and Ptgs2). Some of the markers may be indirect and reliable parameters to assess oocyte competence. The oocyte-produced factors can regulate numerous cumulus cell functions such as cumulus expansion, apoptosis, metabolism (glycolysis and cholesterol synthesis), and these functions are critical in the development of oocyte competence. It is unclear whether oocyte-secreted factors can signal through autocrine pathway to regulate oocyte function. GDF9, growth differentiation factor 9; BMP15, bone morphogenetic protein 15; FGF8B, fibroblast growth factor 8B; Has2, hyaluronan synthase 2; Ptgs2, prostaglandin-endoperoxide synthase 2; Grem1, gremlin 1.