Control of Mammalian Oocyte Development by Interactions with the Maternal Follicular Environment

Development of animal germ cells depends critically on continuous contact and communication with the somatic compartment of the gonad. In females, each oocyte is enclosed within a follicle, whose somatic cells supply nutrients that sustain basal metabolic activity of the oocyte and send signals that regulate its differentiation. This maternal microenvironment thus plays an indispensable role in ensuring the production of fully differentiated oocytes that can give rise to healthy embryos. The granulosa cells send signals, likely membrane-associated Kit ligand, which trigger oocytes within resting-stage primordial follicles to initiate growth. During growth, the granulosa cells feed amino acids, nucleotides, and glycolytic substrates to the oocyte. These factors are necessary for the oocyte to complete its growth and are delivered via gap junctions that couple the granulosa cells to the oocyte. In a complementary manner, growing oocytes also release growth factors, notably growth-differentiation factor 9 and bone morphogenetic protein 15, which are necessary for proper differentiation of the granulosa cells and for these cells to support oocyte growth. During the late stages of oocyte growth, cyclic GMP that is synthesized by the granulosa cells and diffuses into the oocyte is required to prevent its precocious entry into meiotic maturation. Finally, at the early stages of maturation, granulosa cell signals promote the synthesis of a subset of proteins within the oocyte that enhance their ability to develop as embryos. Thus, the maternal legacy of the follicular microenvironment is witnessed by the fertilization of the ovulated oocyte and subsequent birth of healthy offspring.