Do the Theca Layer and Fibroblast Growth Factors Have a Role in Follicular Atresia?1

Abstract

Ovarian follicular development in the bovine estrous cycle is characterized by a wave-like pattern of successive periods of follicle growth and regression, with the majority of estrous cycles in cows comprising either two or three waves per cycle. Each wave involves recruitment of a cohort of antral follicles, followed by selection of a single dominant follicle that progresses to the pre-ovulatory stage, while the remaining follicles of the wave, the subordinate follicles, undergo atresia. The pituitary gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone, are the primary drivers of follicle recruitment and growth, with molecules produced locally within the follicle having secondary but essential roles in dominant follicle selection, while promoting atresia of subordinate follicles [1]. Bidirectional communication between the oocyte and adjacent cumulus granulosa cells results in expansion and mucification of the cumulus-oocyte complex necessary for ovum release at ovulation, mediated by oocyte-secreted peptides (growth differentiation factor 9, bone morphogenic protein [BMP] 15, fibroblast growth factor [FGF] 8) [2, 3]. In turn, molecules from cumulus cells (epidermal growth factor–like peptides, cAMP, and pyruvate) trigger meiotic and cytoplasmic maturation of the oocyte essential for fertilization and embryo development [4]. Similarly, paracrine signals and substrates passing between mural granulosa cells and theca cells of the follicle wall contribute to both granulosa and theca cell proliferation and differentiation essential for continued follicle growth and maturation leading to ovulation. Theca cells supply androgens as precursors for conversion to estrogens by aromatase located exclusively in granulosa cells, and growth factors (insulin-like growth factors [IGFs] and FGFs) that act synergistically with the estrogens to further enhance follicle growth. In turn, estrogens and other growth factors produced by granulosa cells exert regulatory actions back on the theca cells. These closely coordinated activities of the three follicle cell types—oocyte, granulosa cells, theca cells—comprise a regulatory network that results in an intrafollicular milieu necessary for follicle growth and ovulation of a developmentally competent ovum as culmination of the final follicular wave of the cycle [5,