MSc Student
Advisor: Mihaela Pavlicev
Unit for Theoretical Biology, Department of Evolutionary Biology
University of Vienna
Abstract
Aging is a process that underlies tissue and cellular deterioration as well as chronic disease. However, the timing, mechanisms, and stimulation for aging varies across tissues. In mammals, the female reproductive system ages more rapidly, with a decline in function occurring decades prior to other organs. For example, reproductive aging is associated with a decrease in both the number and quality of eggs within the ovaries, which has been a focus of fertility research. In addition, aging can influence the progression of pregnancy and timing of parturition, resulting in complications such as dystocia - difficult, abnormal or dysfunctional labor. In mice, parturition is stimulated by an increase in prostaglandin associated with progesterone withdrawal towards the end of pregnancy. It was previously found by us and others, that progesterone withdrawal is delayed or absent in old mice, leading to defect parturition. In this study, we will investigate the mechanisms through which uterine changes in older mice contribute to the effects of aging on the timing of parturition. We will compare the 3 months (beginning of reproductive maturity) and 8 months (declining reproductive function) old mice immediately before (15.5 days post coitus) and after (17.5 days post coitus) the initiation of normal progesterone withdrawal. In these mice, we will test previously described effects of aging on progesterone and prostaglandin levels with enzyme-linked immunosorbent assays. Next, we will conduct comparative transcriptomics of the maternal-fetal interface to investigate putative mechanisms of faulty hormone regulation of parturition. Finally, we will use immunohistochemistry to localize differentially expressed proteins of interest. Preliminary analysis indicates that delayed progesterone withdrawal also causes impaired cervical remodeling prior to parturition in older mice, further impacting parturition. From these analyses we will investigate how uterine aging contributes to the effects of reproductive aging on parturition.
