Regulation of ovarian function in domestic animals: translational insights into human ovarian dynamics and dysfunction

Abstract

Ovarian follicular development is a tightly regulated, dynamic process coordinated by endocrine, paracrine, neuroendocrine, and vascular mechanisms that together determine follicle recruitment, selection, dominance, and ovulation. In monovulatory mammals, follicular growth occurs in wave-like patterns characterized by the periodic emergence of a cohort of antral follicles, followed by selection of a single dominant follicle. This process is initiated by transient increases in follicle-stimulating hormone, which drive early follicular recruitment and growth, while subsequent deviation in follicular growth rates leads to dominance of a single follicle capable of continued development. The selection and persistence of the dominant follicle depend on the integration of systemic gonadotropin support with intraovarian growth factor signaling. Local regulatory systems within the ovary, including insulin-like growth factor pathways and oocyte-derived factors such as bone morphogenic protein (BMP15) and growth differentiation factor (GDF9), modulate granulosa cell proliferation, differentiation, and steroidogenic activity. These intraovarian signals establish a functional microenvironment that determines follicular fate and ensures coordinated communication between the oocyte and surrounding somatic cells. A critical but often underappreciated component of follicular maturation is vascular remodeling within the follicular wall. As follicles progress toward preovulatory status, localized increases in blood flow enhance delivery of endocrine signals and metabolic substrates while supporting rapid cellular proliferation and steroid hormone synthesis. These vascular changes are closely associated with follicular health and are predictive of developmental competence and ovulatory potential. At the systemic level, reproductive function is governed by pulsatile secretion of gonadotropin-releasing hormone, which regulates luteinizing hormone release and coordinates ovarian activity. This neuroendocrine axis is modulated by hypothalamic networks that integrate metabolic status, environmental cues, and reproductive signals, thereby linking energy balance with fertility. Emerging evidence from transcriptomic and cellular profiling studies further highlights the complexity of ovarian organization, revealing heterogeneity among follicular and stromal cell populations and identifying novel regulatory pathways involved in follicle activation and aging. Together, these findings emphasize that follicular development is not solely hormone-driven but arises from the integration of endocrine signaling, intraovarian communication networks, vascular dynamics, and neuroendocrine regulation. Disruption of any component of this system contributes to impaired folliculogenesis, reduced oocyte quality, and reproductive dysfunction.