Advisor: Mihaela Pavličev

Master's Defensio - Thursday, March 21st 2024, 13:30
SR 5.1, UBB
Djerassiplatz 1, 1030 Vienna

Abstract

In most mammals, reproductive function declines or ceases before the end of their lifespan. Albeit reproductive aging is a well-appreciated phenomenon, its underlying mechanisms are poorly understood. The present work focuses on reproductive aging mechanisms in mice. Early aging complications in reproduction of female mice have been reported to affect late pregnancy and parturition. Thereby, systemic progesterone withdrawal, which is normally caused by luteolysis to trigger parturition, is delayed in older mice. Thus, we hypothesize that the cause for age-related dystocia is likely connected to a defect in luteolysis. Here, we investigate the morphological and molecular mechanisms of PGF2α-induced luteolysis in late murine pregnancy using histology, steroid hormone assays and transcriptome analysis. We show that in ourC57BL/6 mouse line, the corpus luteum of late pregnancy is characterized by autophagosome formation,  and that luteolysis has not occurred at 17.5 days post conception. Comparing ovarian morphology of late pregnant 8-month old and 3-month old mice, we find age-related accumulations of enlarged, hemosiderin-ladenmacrophages. These are considered to be markers of chronic inflammation. In the Corpus luteum, we also find an age-related expression increase of inflammatory marker genes, and an expression decrease of genes related to mitosis checkpoint signaling and DNA replication, which are potential signs of DNA damage. We propose that the 8-month old murine ovary is characterized by inflammaging, which may lead to dysregulation of Progesterone activity due to its own anti-inflammatory properties.