Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with insulin resistance and health risks for mother and offspring. Obesity is also characterized by low-grade inflammation, which in turn, impacts insulin sensitivity. The placenta secretes inflammatory cytokines and hormones that influence maternal glucose and insulin handling. However, little is known about the effect of maternal obesity, GDM and their interaction, on placental morphology, hormones and inflammatory cytokines. In a South African cohort of non-obese and obese pregnant women with and without GDM, this study examined placental morphology using stereology, placental hormone and cytokine expression using real-time PCR, western blotting and immunohistochemistry, and circulating TNFα and IL-6 concentrations using ELISA. Placental expression of endocrine and growth factor genes was not altered by obesity or GDM. However, LEPTIN gene expression was diminished, syncytiotrophoblast TNFα immunostaining elevated and stromal and fetal vessel IL-6 staining reduced in the placenta of obese women in a manner that was partly influenced by GDM status. Placental TNFα protein abundance and maternal circulating TNFα concentrations were reduced in GDM. Both maternal obesity and, to a lesser extent, GDM were accompanied by specific changes in placental morphometry. Maternal blood pressure and weight gain and infant ponderal index were also modified by obesity and/or GDM. Thus, obesity and GDM have specific impacts on placental morphology and endocrine and inflammatory states that may relate to pregnancy outcomes. These findings may contribute to developing placenta-targeted treatments that improve mother and offspring outcomes, which is particularly relevant given increasing rates of obesity and GDM worldwide. KEY POINTS: Rates of maternal obesity and gestational diabetes (GDM) are increasing worldwide, including in low-middle income countries (LMIC). Despite this, much of the work in the field is conducted in higher-income countries. In a well-characterised cohort of South African women, this study shows that obesity and GDM have specific impacts on placental structure, hormone production and inflammatory profile. Moreover, such placental changes were associated with pregnancy and neonatal outcomes in women who were obese and/or with GDM. The identification of specific changes in the placenta may help in the design of diagnostic and therapeutic approaches to improve pregnancy and neonatal outcomes with particular significant benefit in LMICs.

Kisspeptins and Glucose Homeostasis in Pregnancy: Implications for Gestational Diabetes Mellitus-a Review Article.

Gestational diabetes mellitus (GDM) is becoming an increasingly common complication of pregnancy with the global rise of obesity. The precise pathophysiological mechanisms underpinning GDM are yet to be fully elucidated. Kisspeptin, a peptide encoded by the KISS1 gene, is mainly expressed by placental syncytiotrophoblasts during pregnancy. It is an essential ligand for kisspeptin 1 receptor (KISS1R), which is expressed by both the villous and invasive extravillous cytotrophoblast cells. Circulatory kisspeptins rise dramatically in the second and third trimester of pregnancy coinciding with the period of peak insulin resistance. Kisspeptins stimulate glucose-dependent insulin secretion and decreased plasma levels inversely correlate with markers of insulin resistance. Additionally, kisspeptins play a critical role in the regulation of appetite, energy utilisation and glucose homeostasis. GDM pregnancies have been associated with low circulatory kisspeptins, despite higher placental kisspeptin and KISS1R expression. This review evaluates the role of kisspeptin in insulin secretion, resistance and regulation of appetite as well as its implications in GDM.