Tissue-specific HGF and soluble c-MET levels in gestational diabetes mellitus: insights into maternal-endocrine crosstalk and fetal metabolic adaptation.

Objective: Hepatocyte growth factor (HGF)/c-MET signaling regulates glucose metabolism and tissue remodeling, but its role in gestational diabetes mellitus (GDM) remains unclear. We aimed to investigate maternal serum HGF and soluble c-MET (sc-MET) levels, their tissue expression in placenta and maternal visceral adipose tissue, and their associations with obstetric and perinatal outcomes in GDM. Methods: In this retrospective observational, cross-sectional study, 76 pregnant women (32 GDM, 44 normal glucose tolerance) were enrolled. Serum HGF and sc-MET were measured by ELISA; placental and visceral-fat HGF/c-MET expression was analyzed by RT-PCR and western blot. Clinical variables, including umbilical-cord blood gas and glucose values, were evaluated. Results: Maternal sc-MET levels were significantly higher, and cord-blood HGF levels significantly lower, in the GDM group. HGF protein expression was increased in maternal visceral fat but unchanged in placenta. Maternal HGF correlated negatively with cord base excess and positively with lactic acid levels, while cord HGF correlated positively with neonatal glucose. Conclusions: These findings indicate tissue-specific dysregulation of HGF/c-MET signaling in GDM, potentially linking maternal insulin resistance with fetal metabolic stress through visceral-fat-derived HGF. The associations between maternal HGF and neonatal lactic acid levels suggest an endocrine interaction influencing fetal adaptation. Further studies are needed to clarify underlying mechanisms across heterogeneous GDM phenotypes. Plain language summary: GDM is a condition that develops during pregnancy and affects how the body regulates sugar. This study explored how two proteins, HGF and its receptor c-MET, may influence metabolism in mothers with GDM and their babies. Blood, placenta, and visceral fat samples were analyzed from women with and without GDM. Mothers with GDM had higher blood levels of soluble c-MET and lower HGF levels in cord blood. HGF activity was increased in visceral fat, suggesting altered fat metabolism may contribute to insulin resistance. These changes were linked to higher lactic acid levels in newborns, a sign of metabolic stress. The findings suggest that HGF/c-MET signaling helps coordinate hormonal communication between mother and fetus during pregnancy and could serve as a potential biomarker for maternal insulin resistance and fetal metabolic health in GDM.