17-Beta Estradiol in obese pregnancies

INTRODUCTION Maternal obesity (MO) impacts on pregnancy and fetal outcomes, possibly altering intrauterine programming leading to adulthood diseases. Its energetic imbalance results in increased circulating fatty acids and consequent inflammation and oxidative stress. MO has been associated to both systemic and hormonal changes, but the metabolic impact of excessive fatty acids on pregnancy is not fully understood. Estrogens physiologically regulating pregnancy-related insulin resistance may also exacerbate obesity-related inflammation. During pregnancy the fetal-placental unit becomes a primary source of estrogens, particularly of 17-Beta Estradiol (E2). An obesity-related impairment of placental steroidogenesis has been reported. We measured maternal plasma E2 in relation to pregestational BMI and gestational diabetes mellitus (GDM). METHODS Venous blood was collected at elective cesarean section from 24 normal-weight (NW) and 23 obese (OB) women, 8 with GDM [OB/GDM(+)] (75 gr-OGTT; FIGO guidelines). EDTA samples were centrifuged at 1,500 rpm x 15 min and plasma selected excluding hemolyzed, icteric and lipemic. Samples were diluted 1:10 and run in duplicate on Cobas e411 to measure E2 concentration by an electrochemiluminescence immunoassay. Clinical and molecular data were analyzed with t-test and Pearson correlation. RESULTS When comparing to NW, maternal BMI was significantly different in OB (p ≤ 0.001), while basal glycaemia only in OB/GDM(+) (p ≤ 0.001) following inclusion criteria. Placental weight and thickness were significantly higher in both OB groups vs NW (p < 0.01), while efficiency (fetal/placental weight) was decreased in OB [6.68 ± 1.07] (p < 0.01) vs NW [8.01 ± 2.03]. E2 concentration [pg/mL] resulted significantly lower in OB [17,593.2 ± 5,493.6] vs NW [23,049.8 ± 11,810.1] (p ≤ 0.05). When considering the presence of GDM, OB/GDM(+) [19,701.9 ± 4,583.9] showed no differences compared to either OB/GDM(-) or NW, while OB/GDM(-) [16,468.5 ± 5,746.6] confirmed significantly lower E2 plasma concentration vs NW (p < 0.05). E2 levels correlated negatively with maternal BMI (p = 0.04, r = -0.30) and positively with placental efficiency (p = 0.01, r = +0.36) (Fig. 1). CONCLUSIONS Our preliminary analyses support evidences linking excessive BMI to decreased plasma E2, possibly impacting pregnancy outcomes. Indeed, E2 exerts a protective role against oxidative-stress, and obese lipotoxic environment can lead to decreased placental efficiency. GDM metabolic impairments related to insulin-resistance might represent an additional-opposing factor to the obese context, leading to increased E2 levels. Experiments on placental Estrogen Receptors (ER) will investigate a causal link to plasma E2 variation. Exploring the obesity-related effect on placental estrogen pathways could open future therapeutic features.