Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts.

Relaxin promotes softening of the uterine cervix and inhibits uterine contractility in rats, mice and pigs. Little information, however, is available about the role of relaxin in humans. In 2002, LGR7 and LGR8 were discovered to be receptors for relaxin and those receptors were identified in the human placenta. Thus, in this study, effects of recombinant H2 (rH2) relaxin on human early placental extravillous trophoblasts (EVTs) were examined. Isolation of EVTs from early placental trophoblasts was performed using the procedures established in our laboratory. After 48-h subculture, the presence of relaxin receptors in cultured EVTs was characterized by RT-PCR and immunoblotting. The cultured EVTs were treated with different doses (0.3-3 ng/ml) of rH2 relaxin for 24 h. The effects of rH2 relaxin on MMP-2, -3, -9 and TIMP-1 mRNAs levels were examined by real-time RT-PCR. RT-PCR and immunoblotting revealed that relaxin receptors are present in early placental EVTs. Treatment with rH2 relaxin increased MMP-2 and -9 mRNAs levels and decreased TIMP-1 mRNA levels in cultured EVTs, whereas rH2 relaxin did not affect MMP-3 mRNA levels. These results suggest that relaxin may promote the invasive potential of early placental EVTs through up-regulating MMP-2, -9 mRNAs and down-regulating TIMP-1 mRNA in EVTs.