MSc Student
Advisor: Mihaela Pavlicev

Unit for Theoretical Biology, Department of Evolutionary Biology
University of Vienna

Abstract

Age-related complications in pregnancy can occur long before the onset of reproductive senescence (menopause). For example, the prevalence of dystocia (abnormally long labor and aggravated child delivery) increases steadily between ages 25 and 40. In mice, a model system for reproduction in humans and placental mammals in general, an increase of pregnancy complications occurs at comparable ages. Indeed, a recent investigation of pregnancy in 8-month-old mice (being the equivalent of 32-35 years in humans) described severe dystocia, ending in both maternal and offspring death in one out of four cases. The older mice were found to have a delay in progesterone withdrawal that lead to impaired uterine contractility and erratic pulses. We follow up on these findings to investigate the mechanisms through which age and age-related changes in progesterone signaling can result in adverse reproductive outcomes. At term, labor is induced by the endometrially produced hormone PGF2α. It initiates luteolysis to terminate progesterone synthesis in the ovary, metabolizes extant progesterone and thus induces labor. Contrary to initial expectations, hormone measurements at 15.5 and 17.5 days post fertilization (before and at the PGF2α peak associated with parturition) from our group revealed that PGF2α levels in older mice are not diminished, but even elevated. In our ongoing research we are investigating age-related differences in ovarian morphology and signalling pathways affecting progesterone levels in parturition, namely differential expression of genes downstream of PGF2α or upstream of progesterone.