During pregnancy, the mother must adapt her body systems to support nutrient and oxygen supply for growth of the baby in utero and during the subsequent lactation. These include changes in the cardiovascular, pulmonary, immune and metabolic systems of the mother. Failure to appropriately adjust maternal physiology to the pregnant state may result in pregnancy complications, including gestational diabetes and abnormal birth weight, which can further lead to a range of medically significant complications for the mother and baby. The placenta, which forms the functional interface separating the maternal and fetal circulations, is important for mediating adaptations in maternal physiology. It secretes a plethora of hormones into the maternal circulation which modulate her physiology and transfers the oxygen and nutrients available to the fetus for growth. Among these placental hormones, the prolactin-growth hormone family, steroids and neuropeptides play critical roles in driving maternal physiological adaptations during pregnancy. This review examines the changes that occur in maternal physiology in response to pregnancy and the significance of placental hormone production in mediating such changes.

Genetic engineering of the mouse genome identified many genes that are essential for embryogenesis. Remarkably, the prevalence of concomitant placental defects in embryonic lethal mutants is highly underestimated and indicates the importance of detailed placental analysis when phenotyping new individual gene knockouts. Here we introduce high-resolution contrast-enhanced microfocus computed tomography (CE-CT) as a nondestructive, high-throughput technique to evaluate the 3D placental morphology. Using a contrast agent, zirconium-substituted Keggin polyoxometalate (Zr-POM), the soft tissue of the placenta (i.e., different layers and cell types and its vasculature) was imaged with a resolution of 3.5 µm voxel size. This approach allowed us to visualize and study early and late stages of placental development. Moreover, CE-CT provides a method to precisely quantify placental parameters (i.e., volumes, volume fraction, ratio of different placental layers, and volumes of specific cell populations) that are crucial for statistical comparison studies. The CE-CT assessment of the 3D morphology of the placentas was validated (i) by comparison with standard histological studies; (ii) by evaluating placentas from 2 different mouse strains, 129S6 and C57BL/6J mice; and (iii) by confirming the placental phenotype of mice lacking phosphoinositol 3-kinase (PI3K)-p110α. Finally, the Zr-POM–based CE-CT allowed for inspection of the vasculature structure in the entire placenta, as well as detecting placental defects in pathologies characterized by embryonic resorption and placental fusion. Taken together, Zr-POM–based CE-CT offers a quantitative 3D methodology to investigate placental development or pathologies.

Aim The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. Methods Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high‐resolution respirometry, stereology, and molecular analyses. Results Diet‐induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein‐2 was decreased by maternal obesity in both fetal sexes. Conclusion Maternal obesity exerts sex‐dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women.

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Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however the intrauterine mechanisms involved remain unknown. This study in the rat assessed the impact of advanced maternal age on placental phenotype in relation to the growth of female and male fetuses. We show that relative to young (3–4 months) dams, advanced maternal age (9.5–10 months) compromises growth of both female and male fetuses but affects the placental phenotype sex-specifically. In placentas from aged versus young dams, the size of the placental transport and endocrine zones were increased and expression of Igf2 (+41%) and placental lactogen (Prl3b1: +59%) genes were upregulated in female, but not male fetuses. Placental abundance of IGF2 protein also decreased in the placenta of males only (−95%). Moreover, in placentas from aged versus young dams, glucocorticoid metabolism (11β-hsd2: +63% and 11β-hsd1: −33%) was higher in females, but lower in males (11β-hsd2: −50% and 11β-hsd1: unaltered). There was however, no change in the placental abundance of 11β-HSD2 protein in aged versus young dams regardless of fetal sex. Levels of oxidative stress in the placenta were increased in female and male fetuses (+57% and +90%, respectively) and apoptosis increased specifically in the placenta of males from aged rat dams (+700%). Thus, advanced maternal age alters placental phenotype in a sex-specific fashion. These sexually-divergent changes may play a role in determining health outcomes of female and male offspring of aged mothers.