engleski

Sex-specific interrelation between glucose levels and SLC6A4 gene methylation in maternal and fetal blood

Serotonin (5-HT) regulates glucose homeostasis during pregnancy by promoting proliferation1 and activity2 of insulin-producing β-cells. Dysregulation of these mechanisms can lead to maternal hyperglycemia and gestational diabetes mellitus (GDM). GDM is more common in women carrying a male fetus, 3 but the mechanisms by which fetal sex affects glucose homeostasis are not clear. Here we investigated the relationship between methylation of the gene encoding the 5-HT transporter (SLC6A4), an important regulator of extracellular 5-HT levels, and glucose levels in maternal and cord blood, considering the possible influence of fetal sex. The study included 129 mother-infant dyads from the ongoing Placental and Neonatal Serotonin (PlaNS) cohort study in Zagreb, Croatia. Maternal glucose levels in the 2nd trimester of pregnancy were obtained from medical records, fetal glucose levels were measured in cord blood. SLC6A4 gene methylation was quantified in maternal and cord blood cells by bisulfite pyrosequencing. In pregnancies with a female fetus (n=50), maternal glucose levels correlated negatively with maternal SLC6A4 methylation (r=-0.43, p<0.01) and positively with cord blood glucose (r=0.34, p<0.01) levels, while cord blood SLC6A4 methylation did not correlate with maternal or cord blood glucose levels. In pregnancies with a male fetus (n=79), maternal glucose levels did not correlate with either maternal or cord blood SLC6A4 methylation or with cord blood glucose levels. However, a negative correlation was observed between cord blood glucose and SLC6A4 methylation levels (r=-0.40, p<0.01). The results show a fetal sex-dependent association of glucose and SLC6A4 methylation levels in both mother and fetus. In women carrying a female fetus, lower SLC6A4 methylation may confer a higher risk of developing GDM. In male fetuses, fetal glucose levels may modulate SLC6A4 methylation, potentially affecting the child's lifelong health.

SLC6A4 ; GDM ; methylation ; pregnancy ; fetal sex

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