Advanced Maternal Age and Fetal Sex Modulate Placentokines and Metabolic Glucose Biomarkers

Background Advanced maternal age (AMA) is linked to an increased risk of obstetrical issues. Research to date has investigated the role of several placentokines related to adipose signalling and glucose metabolism biomarkers in pregnancy outcomes; however, AMA and neonatal sex are crucial factors that have not been considered in the study of metabolic function during pregnancy. The objective of this research was to elucidate the influence of AMA and neonatal sexual dimorphism on these placentokines and glucose homeostasis together with their possible relationships with the anthropometric characteristics of newborns. Methods A cohort of 184 nulliparous pregnant women were divided by age (≥ 35 years) and control (< 35 years). The expression of all biomarkers included in the analysis was measured in placental tissue. Results Insulin and visfatin levels were greater in the AMA group, whereas glucagon, PAI-1, resistin, and leptin levels were lower. In placentas from male AMA, insulin levels were higher and glucagon, leptin and resistin levels were lower than those in placentas from male control fetuses. Leptin levels were also lower in placentas from AMA male fetuses than in those from AMA female fetuses in both groups. Moreover, placental alterations associated with maternal age and fetal sex are correlated with distinct neonatal anthropometric parameters. Conclusions Nulliparous AMA mothers exhibit changes in placental metabolic signalling influenced by neonatal sexual dimorphism, with more pronounced effects in male neonates. These effects could influence fetal development and postnatal life.