BACKGROUND AND PURPOSE: Pre-eclampsia is a serious clinical gestational disorder occurring in 3%–5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. MATERIALS AND METHODS: Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. RESULTS: Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. CONCLUSIONS: This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies.

Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.

We aimed to assess the expression of key angiogenic factors of the VEGF family in the term placenta of women based on physical activity status. The expression of VEGF and VEGFR‐1 was higher in placen...

The physiological and molecular mechanisms linking prenatal physical activity and improvements in maternal–fetal health are unknown. It is hypothesized that small extracellular vesicles (EVs, ~ 10–120 nm) are involved in tissue cross-talk during exercise. We aimed to characterize the circulating small EV profile of pregnant versus non-pregnant women after an acute bout of moderate-intensity exercise. Pregnant (N = 10) and non-pregnant control (N = 9) women performed a single session of moderate-intensity treadmill walking for 30 min. Plasma was collected immediately pre- and post-exercise, and small EVs were isolated by differential ultracentrifugation. EV presence was confirmed by western blotting for the small EV proteins TSG-101 and flottilin-1. Small EVs were quantified by size and concentration using nanoparticle tracking analysis and transmission electron microscopy. All EV fractions were positive for TSG-101 and flotillin-1, and negative for calnexin. Mean vesicle size at baseline and percent change in size post-exercise were not different between groups. At baseline, pregnant women had higher levels of small EVs compared to controls (1.83E+10 ± 1.25E+10 particles/mL vs. 8.11E+09 ± 4.04E+09 particles/mL, respectively; p = 0.032). Post-exercise, small EVs increased significantly in the circulation of pregnant compared to non-pregnant women after correcting for baseline values (64.7 ± 24.6% vs. − 23.3 ± 26.1%, respectively; F = 5.305, p = 0.035). Further research is needed to assess the functional roles of exercise-induced small EVs in pregnancy.