The Role of Different Lymphoid Cell Populations in Preeclampsia Pathophysiology.

Preeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, PE has no cure beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation; intrauterine growth restriction; uterine artery resistance; dysregulation of the renin-angiotensin system. Which contributes to renal dysfunction; and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling, resulting in decreased placental perfusion and thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in proinflammatory and anti-inflammatory cell types in women with PE and in animal models used to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases, such as cardiovascular disease, CKD, dementia during the postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.

Dysregulated appetitive leptin signaling in male rodent offspring from post-bariatric dams.

Bariatric surgery produces significant positive benefits to recipients such as significant body fat loss and resolution of the various obesity-related comorbidities, such as reduced reproductive function. Females of childbearing age seek bariatric surgical remedies to improve their chance of successful pregnancy; however, limited knowledge exists on the impact of surgical weight loss to subsequently born offspring. We previously reported that circulating leptin levels were reduced in pregnant females having previously received vertical sleeve gastrectomy (VSG) in comparison to control dams having received Sham surgery. Furthermore, the levels of leptin receptors in the VSG placenta were also reduced in VSG. These data suggest a significant difference in leptin signaling during pregnancy that may produce an altered developmental environment for the offspring. Here, we investigate the adult offspring of dams having received VSG or Sham-VSG prior to pregnancy. Endogenous fasting plasma leptin levels were not different between Sham and VSG offspring. Fasting leptin receptor mRNA in the medial basal hypothalamus (MBH) was elevated in VSG offspring in comparison to Sham. Intraperitoneal administration of exogenous leptin produced reductions in acute food intake in male Sham offspring, but did not reduce food intake at any time point measured in male VSG offspring. Using Western blot, we identified elevated pSTAT3 and pSTAT3/STAT3 ratios in the MBH of post-VSG offspring in comparison to controls. Using immunohistochemistry, we found an increased number of pSTAT positive cells in the arcuate nucleus in the Sham offspring in comparison to VSG. In contrast, within the paraventricular and ventromedial nuclei in the hypothalamus of the VSG offspring had elevated numbers of pSTAT-positive cells in comparison to controls. Collectively, these data support our hypothesis that leptin signaling is dysregulated in VSG offspring and may be partially responsible for the long-term impact of maternal bariatric surgery on the metabolic health of offspring.

Nutrient and hormone composition of milk is altered in rodent dams post-bariatric surgery.

Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.