DESCRIPTION (provided by applicant): Ovarian follicles undergo a highly orchestrated recruitment and selection process under both endocrine and paracrine regulatory mechanisms, such that by the completion of the process, one or more follicle-enclosed oocytes are prepared for fertilization. During this developmental window, a rich and highly complex fluid containing numerous proteins, miRNAs, and other macromolecules accumulates within the follicular antrum to effectively isolate and simultaneously nurture the cumulus-oocyte-complex (COC). Recent studies have shown that small extracellular vesicles, which include exosomes and microvesicles, are abundant within antral fluid. These vesicles are a rich source of proteins, microRNAs and other molecules that can be taken-up by follicular cells and thus may transmit messages between varying regions within follicular environment. The mere presence of microvesicles and exosomes, which we hereafter refer to collectively as folliculosomes, within the antral follicle, strongly suggests a novel mechanism of communication within the developing follicle. Despite this, no studies have as yet identified any biological function of these vesiclesin ovarian physiology. Therefore, we propose to use folliculosomes collected from antral follicles before and after the LH surge to (1) determine the effects of folliculosomes on maturation and developmental competence of cumulus-oocyte complexes and (2) identify the LH-regulatory mechanism(s) that mediate the rapid changes in folliculosomes prior to ovulation. The central hypothesis of the proposed research is that folliculosomes play critical roles in COC maturation and subsequent developmental competence of the oocyte.

PUBLIC HEALTH RELEVANCE: Normal ovarian follicle function is critical for generation of a viable, fertilizable oocyte and therefore fertility. Small extracellular vesicles have recently bee detected in the follicular antral fluid; the current proposal will investigate the functional significance of this unique vesicular mediated cell communication mechanism. The long-term benefits of this research will enhance our understanding of ovarian function and has real potential to impact and improve the procedures and processes used in the treatment of infertility.