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 TNF alpha 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 TNF alpha 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 TNF alpha protein abundance and maternal circulating TNF alpha 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.

Automated summary

This study examined the effects of maternal obesity and gestational diabetes mellitus (GDM) on placental morphology, hormone and cytokine expression, and circulating inflammatory cytokine concentrations. The results showed that both obesity and GDM had specific impacts on placental morphometry and endocrine and inflammatory states, which may be related to pregnancy outcomes.