Gestational diabetes mellitus placentas exhibit epimutations at placental development genes.

Gestational diabetes mellitus (GDM) is a maternal metabolic disorder that perturbs placental development and increases the risk of offspring short- and long-term metabolic disorders. The mechanisms by which GDM impairs placental development remain poorly understood. Here, we defined the DNA methylome of GDM placentas and determined whether GDM perturbs methylation at genes important for placental development. We conducted an epigenome-wide association study of 42 placentas from pregnancies in the South African Soweto First 1000 days cohort (S1000). Using genome-wide bisulfite sequencing, we compared non-GDM placentas to GDM placentas with similar proportions from obese and non-obese mothers. Compared to non-GDM, GDM placentas exhibited a distinct methylation profile consisting of 12,210 differentially methylated CpGs (DMCs) that mapped to 3,875 genes. Epigenetically altered genes were enriched in Wnt and cadherin signalling pathways, both critical in placentation and embryogenesis. We also defined regional DNA methylation perturbation in GDM placentas at 11 placental development genes. These findings reveal extensive changes to the placental epigenome of GDM pregnancies and highlight perturbation enriched at important placental development genes. These molecular changes represent potential mechanisms for GDM-induced placental effects that may serve as candidate biomarkers for placental, maternal, and foetal health. Using a study design that used similar proportions of obese and non-obese mothers in our case and control pregnancies, we minimized the detection of changes due to obesity alone. Further work will be necessary to investigate the extent of the influence of obesity on these GDM-related placental epigenetic changes.

Assessment of placental metal levels in a South African cohort.

The placenta plays an important role in mediating the effect of maternal metal exposure on fetal development, acting as both barrier and transporter. Term-placenta metal levels serve as an informative snapshot of maternal/fetal exposure during pregnancy and could be used to predict offspring short- and long-term health outcomes. Here, we measured term-placenta metal levels of 11 metals in 42 placentas from the Soweto First 1000 days cohort (S1000, Soweto-Johannesburg, SA). We compared these placental metal concentrations with previously reported global cohort measurements to determine whether this cohort is at increased risk of exposure. Placental metals were tested for correlations to understand potential interactions between metals. Since these samples are from a birth cohort study, we also performed exploratory analyses to determine whether metal levels were associated with placenta and birth outcomes. Most S1000 placental metal levels were similar to other cohorts; however, cadmium (Cd) levels up to 50-fold lower, and essential elements nickel (Ni) and chromium (Cr) level up to 6- and 16-fold lower, respectively. Cd, Se, and Ni were associated with placenta and birth outcomes. Studies are ongoing to examine underlying mechanisms and how these developmental differences affect long-term health.

Association between Depression and Aggression in Rural Women.

Rural women represent approximately 20% of women living in the United States, yet research on the specific mental health needs of rural women is limited. Given the well-recognized gender-linked difference in depression rates, its correlated depressive symptoms in women still need much investigation. While emerging notions of depression in men embrace potential symptoms related to irritability and aggression, less research has focused on the potential role of aggression in depressed women. This connection may be particularly relevant for rural women who face unique mental health stressors in comparison to their urban counterparts. The purpose of this study was to examine if aggression is linked to depression for rural women in order to identify potential unique symptomatology and presentation for rural women. As part of a larger initiative, a sample of 54 participants was recruited from the patient population at a Federally Qualified Health Center (FQHC) in rural southeast Georgia to participate in a quantitative survey. The survey explored demographics, depression, and aggressive behavior. Mean total score of aggression in depressed women was significantly higher than non-depressed women (p < 0.001), and within the entire sample depression scores were significantly related linearly to aggression, with aggression explaining 16% of the variance found in depression scores (ß = .399, r2 = .159, p = 0.003). This study suggests that aggressive behavior may be linked to depression for rural women, and underscores the need for future research investigating if depression presents differently for rural women.