Effect of maternal age on incidences of apoptotic and proliferative cells in trophoblasts of full-term human placenta

Advanced maternal age is known to be a risk factor for various kinds of obstetric complications, including placental dysfunction. As a first step towards determining the maternal age-related changes in placental, as well as trophoblastic function, we examined the incidences of apoptotic and proliferative cells in trophoblasts of placentae from women of various ages using the TUNEL method and immunohistochemistry for Ki-67 antigen. Tissue sections were collected from the placentae of healthy mothers, with normal delivery of healthy babies so that the placental cell kinetics maintaining normal pregnancy and delivery could be studied. The TUNEL-positive cells of the placenta were syncytiotrophoblasts with clustering of nuclei and the TUNEL-positive index of these cells varied from 0.28-1.2%. This index revealed a significant inverse correlation with maternal age. In contrast, the Ki-67-positive index of mononuclear trophoblasts of the placenta ranged between 1.2-2.8% and showed a positive correlation with maternal age. Many of the apoptotic cells of placental villi expressed the pro-apoptotic Bak protein, but were negative for expression of the, anti-apoptotic Bcl-2 protein. These results suggest that trophoblasts have higher proliferative activity in older mothers, with a normal process of pregnancy and delivery. The Bcl-2 family proteins could be important for the regulation of trophoblastic apoptosis, although the cellular and molecular mechanisms mediating maternal age-related changes of the placenta remain to be determined.