Contraction-associated proteins expression by human uterine smooth muscle cells depends on maternal serum and progranulin associated with gestational weight gain.

Abstract

Pregnant women with obesity are at increased risk of parturition dysfunction; however, the biological mechanism has remained unknown. We hypothesized that molecules circulating in the serum of pregnant women with obesity may induce the aberrant expression of contraction-associated proteins (CAPs), leading to insufficient uterine contractions. This study aimed to investigate the effects of maternal serum on CAPs expression by human uterine smooth muscle cells (UtSMCs) and elucidate the influence of maternal obesity. Blood samples were collected from singleton pregnant women at 36-41 weeks of gestation before the onset of labor. UtSMCs were incubated in the serum, and the mRNA expressions of PTGFR, OXTR, GJA1, and PTGS2 were examined by RT-PCR. Progranulin (PGRN) is a circulating glycoprotein associated with insulin resistance characterized by the accumulation of visceral fat. The serum PGRN levels of the samples were measured by ELISA. After incubated with PGRN (100-1,000 ng/mL), mRNA expression of PTGFR, OXTR, and GJA1 and protein expression of CX43 were examined by RT-PCR and western blotting, respectively. The mRNA expressions of PTGFR, OXTR, and GJA1 showed significantly negative correlations with gestational weight gain (GWG). Serum PGRN levels showed a significantly positive correlation with GWG. High levels of PGRN suppressed the mRNA expression of GJA1 and the protein expression of CX43. The change in maternal serum induced by GWG suppressed the CAPs expression by UtSMCs. PGRN is one of the factors in the serum responsible for inhibiting the expression of CX43.