The Role of CISD2 in the Female Reproductive System of Mammal

Aging has been the major challenge for those advanced age women who’s wanted to conceive naturally as well as for the clinical doctors at infertility treatment. This is because a successfully nature conception or even the good IVF or other ART outcome often depends on the quality of eggs and retrieval of sufficient number of eggs from the patients. Unfortunately, these two factors are associated with ovarian function that particular vulnerable by aging. This is because, it has been long thought that number of eggs containing in the ovary is already determined at fetal life. Those eggs will stay arrest for decades in the ovary till ovulation upon sex mature at puberty and ceases at menopause. Because of this long journey, mammal eggs are therefore prone for errors, thus has big impacts on embryonic development, such as the rate of getting Down-syndrome baby increases by maternal-age. Therefore to understand the detail molecular mechanism that underlying aging-associated ovarian function and on eggs quality are fundamental for reproductive medicine. A recent identified gene, CISD2 (CDGSH iron sulfur domain) as it was named, it belongs to CDGSH iron sulfur domain-contained gene family; it is a mitochondrial-located protein that was recently found to be associated with controlling lifespan in mammal. By generating the CISD2 deficiency mice, in this particular pioneer study, they demonstrated that insufficient CISD2 leads to premature ageing in many aspects, with all mitochondrial-associated defects phenotype, and the female CISD2 KO mice seems to infertile. In addition, mitochondrial is maternal inherited, thus, this is of interest to us, since the pioneer study did not demonstrate any reproductive function related data. Thus, in the current research proposal, we aim to achieve at least 3 goals that are: (1) to determine whether CISD2 acts a critical role in regulating ovarian function as well as eggs quality; (2) The involvement of CISD2 in impairing the fertilization as its role in maintaining Ca2+ homeostasis; (3) If so, how could we modulate its regulation to improve the better outcome for infertility treatment. The significant of this project that is to elucidate whether insufficient of CISD2 leads to premature aging syndromes in the reproductive system that would consequence contributes to infertile in mammal. It would provide practical information to the future reproductive medicine.