Stillbirth refers to the in-utero death of a fetus after 20 weeks of gestation. While a typical human pregnancy lasts between 37 and 41 weeks, the risk of stillbirth significantly increases when pregnancy extends beyond 40 weeks. Although some post-term stillbirths have identifiable causes, most remain unexplained. We propose that a common mechanism may underlie antepartum stillbirths late in pregnancy. Research indicates that human placentas from post-term (41+ weeks) and stillbirth pregnancies exhibit signs of aging, such as shortened telomeres, oxidative damage to lipids and DNA/RNA, and dysregulated autophagy. Given these aging-associated changes in post-term placentas, we hypothesise that placental aging contributes to the increased rate of stillbirths observed in post-term pregnancies.
The study aims to prolong gestation by preventing the onset of labour in pregnant mice, investigate changes in the placenta, and monitor fetal outcomes.
From embryonic day E17.5, pregnant CD1 Swiss mice received daily progesterone or promegestone injections until E21.5 or the delivery of the pups. To assess fetal and placental outcomes, we collected data on the number of viable fetuses and placentas for analysis of oxidative damage.
We successfully extended mouse pregnancy to E21.5 and E22.5 by administering daily injections of progesterone (25mg/day) or promegestone (0.2mg/day) starting from E17.5. Our data indicate that this model results in a high rate of fetal death (87% in the progesterone group and 77% in the promegestone group). We observed increased lipid peroxidation in post-term placentas (progesterone), consistent with findings in post-term and stillbirth human placentas, as well as a shrunken and degenerated placental glycogen layer.
Prolonging pregnancy makes the murine fetus susceptible to significant fetal death due to placental aging. Our findings are consistent with human cases, suggesting that our prolonged pregnancy mouse model is a valuable tool for developing therapeutics to prevent placental oxidative damage and reduce fetal death.