(325) Elucidating the Role of Progesterone Signaling in the Rete Ovarii

Lillian Folts1; Anthony S. Martinez1; Wendy Zhang1; Jennifer McKey1*

1. Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract Text: The ovaries are critical for endocrine function and fertility in females.Therefore, there is an urgent need to understand factors that regulate ovarian health. The rete ovarii (RO), a poorly characterized epithelial appendage to the ovary, has emerged as a potential modulator of ovarian health. Our preliminary data suggest that the RO may play a role in progesterone (P4) signaling. P4 is a steroid hormone critical for many reproductive functions, including menstrual cycle regulation, embryo implantation, and lactation. Analysis of single nuclei-RNA sequencing of the adult mouse RO revealed that pgr, the gene encoding progesterone receptor (PGR), is expressed in the RO. Spatial validation showed that PGR is expressed in the smooth muscle sheath that surrounds the epithelial layer of the RO, and this expression does not change across the estrous cycle. PGR expression, and more specifically expression of different isoforms of PGR, is tightly controlled in the female reproductive tract to allow for dynamic downstream actions of P4 in specific cell types. However, it is unknown how P4 acts in the RO. We are currently investigating the role and mechanisms of progesterone signaling in the function of the rete ovarii. Using an ex vivo culture system and live imaging, we are determining whether the RO is responsive to P4. By live imaging explants after P4 treatment, we can determine if the smooth muscle sheath contracts with or without addition of P4. We are also collecting culture media after treatment to identify proteins secreted by the RO in response to P4 treatment. In parallel, we are studying the expression of PGR isoforms and will determine their downstream genomic targets in the RO. These experiments will reveal how the RO responds to P4 and will elucidate a mechanism by which the RO may influence ovarian homeostasis. This work is funded by NIH #R00HD103778 and #T32TR004367.