In vivo imaging of ovulation and follicular atresia in young and aged mice

• Applicant: Dr. Fitore Kusari, Ph.D.
• Subject Area: Reproductive Medicine, Urology ; Developmental Biology ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545896545

Ovarian aging is a major risk factor for infertility, birth defects, and cancer. This process is characterized by a decline in both the number and quality of oocytes. The underlying causes of ovarian aging remain largely unknown, but there is evidence that intrinsic processes such as ovulation could play a role. Ovulation releases egg(s) for fertilization from the ovary throughout the reproductive lifespan of female mammals. While essential for fertility, ovulation can be harmful in the long term. Studies suggest that repeated ovulations impair oocyte quality, but its influence on oocyte viability remains unknown. Considering the gaps in our understanding of the causes and mechanisms behind oocyte atresia and its acceleration with age, it becomes imperative to investigate if ovulation drives these processes. Ovulation in intact mouse ovaries cannot yet be achieved under in vitro conditions. We thus aim to conduct in vivo studies, to test whether ovulation cycles decrease oocyte viability leading to increased attrition with age. To investigate this hypothesis we have two main aims: In Aim 1 we propose to adopt an in vivo imaging system to study ovulation in mice. We have established this system already in euthanized mice and plan to extend its application to mice under anesthesia. We will implant windows over transgenic fluorescent ovaries to image ovulation using high-resolution microscopy in anesthetized mice. In Aim 2 we will use the ovarian in vivo system established under Aim 1 to investigate whether oocytes near ovulation sites undergo atresia and if this promotes ovarian aging. This study first will lead to important advancements in technology by establishing imaging assays that will enable us, and others, to study processes driving ovarian aging in vivo. Second, it can offer insights into whether ovulation leads to oocyte cell death or atresia. If indeed atresia is triggered by ovulation, this will lay the groundwork for subsequent research in mitigating these harmful effects induced by ovulation cycles, with potential implications for fertility preservation.

• DFG Programme: Research Grants