Developmental and functional landscape of theca cells in ovarian biology

Ovarian theca cells constitute essential components of the follicular microenvironment and play central roles in follicular development, steroidogenesis, and endocrine regulation. Despite their significance, the developmental origins, differentiation processes, and functional dynamics of theca cells remain incompletely defined, particularly in humans. This review provides an updated synthesis of current knowledge on the ontogeny, molecular signaling pathways, and intercellular interactions of theca cells. It also presents recent findings on the role of theca stem or progenitor cells and their relevance to reproductive disorders, including polycystic ovary syndrome (PCOS), hyperthecosis, and ovarian insufficiency. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science through May 2025. Search terms included "theca cells," "theca progenitors," "follicular development," "ovarian differentiation," "steroidogenesis," and "reproductive disorders." Original research articles and reviews providing mechanistic insights were included. Current evidence indicates that several signaling pathways, including IGF, SCF, FGF, members of the TGF-β superfamily, GDF9, BMPs, and Hedgehog proteins, are involved in the recruitment, proliferation, and differentiation of theca cells. Bidirectional communication among oocytes, granulosa cells, and theca cells remains essential for folliculogenesis. Increasing evidence links theca cell dysfunction to the pathophysiology of PCOS, primary ovarian insufficiency, and reproductive aging. The identification of theca stem cells (TSCs) and their proposed roles in ovarian regeneration represents an important conceptual advance. A deeper understanding of theca cell biology may guide the development of targeted strategies for infertility and ovarian dysfunction. In contrast, the integration of TSC biology offers new directions for reproductive medicine and reproductive health.