Wednesday, February 5, 2025
2/5/2025
PROJECT SUMMARY Fertility in sexual reproducing organisms requires the formation of both sperm and oocyte. One crucial function of the female germline is the production of high-quality oocytes, which requires both an accurately replicated genome and full complement of cytoplasmic components. Infertility or progeny with diseases can be caused by poor quality of oocytes. Understanding how the female germline can respond to environmental stresses to maintain oocyte quality is important for assessing how infertility occurs in some individuals. As in the human ovary, the C. elegans hermaphrodite oogenic germline produces many more oogenic germ cells than mature oocytes. In C. elegans, >50% of oogenic nuclei are lost prior to oocyte formation through apoptosis. Apoptosis can contribute to oocyte quality through two main mechanisms: removal of low-quality germ nuclei and addition of cytoplasmic resources to the remaining oocytes. Several environmental stressors, including moderate temperature stress, lead to an increase in germline apoptosis without inducing DNA damage. One of the central players necessary for promoting germline apoptosis is LIN-35, the sole C. elegans homolog of mammalian retinoblastoma. Our preliminary data indicate that the MuvB core of the DREAM complex, which is known to interact with LIN-35/Rb, also promotes increased germline apoptosis in response to moderate temperature stress. Our hypothesis is that moderate stress activates apoptosis through LIN- 35/MuvB core to ensure progeny fitness. To investigate this hypothesis, this research project will build on our expertise in DREAM complex biology and germline temperature response. We propose three specific aims to investigate the molecular mechanisms of increased apoptosis under moderate temperature stress and the links between apoptosis and progeny fitness: (1) How does apoptosis in germlines under moderate temperature stress contribute to changes in nuclear or cytoplasmic quality in the oogenic germline? (2) How does LIN-35/MuvB promote apoptosis under moderate temperature stress? (3) Can apoptosis contribute to fertility and fitness in response to moderate temperature stress? This work will define the signaling pathways that induce increased apoptosis, the direct effects of apoptosis on germ cell quality and function, and the long-term effects on fertility and population fitness of increased apoptosis under moderate temperature stress, defining pathways that can be explored to understand infertility.
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