A novel role of corpus luteum in female reproduction

Project summary Approximately 17.5% of the adult population, or roughly 1 in 6 individuals worldwide, experience infertility, underscoring the urgent need to enhance accessibility to affordable, high-quality fertility care, as indicated in the most recent World Health Organization (WHO) report. The corpus luteum (CL), often referred to as the "yellow body," is a dynamic structure that forms during each estrous cycle and plays a critical role in reproduction across various species, including humans. For decades, research on the corpus luteum has primarily focused on its role in pregnancy regulation, suppression of HPG axis, and luteal lysis in mammals. However, it is unclear whether CL plays any other functions that is more fundamental than its role in regulating implantation and pregnancy. CL is not an unique structure in mammalian ovaries. CL is also found in lower vertebrates and invertebrates, such as reptiles and insects. The first study on insect CL was described in 1954 by an Italian scientist. In insects, CL was found in a varies of species including termites, cockroaches, houseflies, horseflies, and butterflies. In additional, our recent work demonstrates that fruit flies (Drosophila melanogaster) also forms CLs from remnants of the ovulated follicles, which show yellowish pigmentation. It is unlikely that CLs in lower vertebrates and insects functions to regulate implantation and pregnancy; however, their roles in reproduction are completely unknown. Such roles could be more fundamental and conserved throughout metazoans. The powerful genetic tools and many conserved reproductive processes including ovulation and CL formation makes the Drosophila an ideal model to investigate the fundamental roles of insect CLs. From our ongoing experiments, we discovered an exciting phenomenon: Debris of Drosophila CL is translocated and concentrated at the anterior half of germarium, which houses both germline stem cells (GSCs) and follicle stem cells (FSCs) and regulates germline development and follicle formation. In addition, some of the CL debris is found inside the hemocytes, Drosophila equivalent of macrophages. Given these findings, we hypothesize that debris of Drosophila CL is translocated by hemocytes to the germarium to alter the stem cell niche function and influence stem cell behavior and follicle formation. In this explorative project, we will first characterize the mechanism that mediates the translocation of the CL debris to the germarium (Aim1) and then determine the role of CL debris in stem cell behavior and folliculogenesis (Aim2). The work proposed here will lead to the discovery of the novel and conserved roles of CL throughout the metazoan.