LAUSR

INTRODUCTION Fetal macrosomia has confirmed be related to multiple labor complications and metabolism syndromes later in life. However, the mechanism of fetal macrosomia in normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) pregnant women is still obscure. This study aimed to investigate the mechanism of Rho guanine nucleotide exchange factor 11 (ARHGEF11) and the insulin signaling pathway in placenta affecting fetal overgrowth in NGT and GDM pregnant women. METHODS Eighty-nine pregnant women with paired antepartum BMI were recruited and divided into four groups: NGT with normal birth weight (NGT-N, n = 30) or macrosomia (NGT-M, n = 22) and GDM with normal birth weight (GDM-N, n = 22) or macrosomia (GDM-M, n = 15). Placenta tissue was collected to examine the expression of ARHGEF11, ROCK1, the phosphorylation of Tyr612 IRS-1 (p-Y612), Ser307 IRS-1 (p-S307), PI3K, AKT, pAKT, GLUT4 and S6K. RESULTS Gene expression of ARHGEF11, ROCK1, p-S307 and S6K in placenta was significantly increased in the NGT-M group (p < .05). The protein density of ARHGEF11 and ROCK1 was positively correlated with birth weight (p < .001) in the NGT groups. p-Y612, PI3K, pAKT and GLUT4 were significantly decreased in NGT-M, GDM-N and GDM-M group (p < .05). But there was no statistical difference between the two GDM groups. DISCUSSION ARHGRF11 inhibited the insulin signaling pathway in placenta may participated in fetal macrosomia in NGT pregnant women. The insulin signaling pathway was suppressed in GDM placenta, but was not closely related to fetal macrosomia, indicated different mechanism in fetal overgrowth in NGT and GDM pregnant women.