RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth

In brief: Various etiologies can cause uterine myometrium contraction, which leads to preterm birth. This study demonstrates a new functional relationship between the Ras-related C3 botulinum toxin substrate 1 (RAC1) and uterine myometrium contraction in preterm birth. Abstract: Preterm birth (PTB) is a public health issue. The World Health Organization has recommended the use of tocolytic treatment to inhibit preterm labour and improve pregnancy outcomes. Intrauterine inflammation is associated with preterm birth. RAC1 can modulate inflammation in different experimental settings. In the current study, we explored whether RAC1 can modulate spontaneous uterine myometrium contraction in a mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation. Subsequently, we recorded uterine myometrium contraction and examined uterine Rac1 expression in a mouse model of preterm birth and a case in pregnant women by Western blotting analysis. We also measured progesterone levels in the blood serum of mice. Murine myometrium was obtained 12 h post LPS treatment. Human myometrium was obtained at the time of caesarean section. We found that in the LPS-treated group of mice, uterine myometrium contraction was enhanced, protein levels and activation of RAC1 were increased and serum progesterone levels were decreased. The protein levels of RAC1 were also increased in preterm birth and in pregnant women. NSC23766, a RAC1 inhibitor, attenuated uterine myometrium contraction and diminished RAC1 activation and COX-2 expression. Furthermore, silencing of RAC1 suppressed cell contraction and COX-2 expression in vitro. In conclusion, our results suggested that RAC1 may play an important role in modulating uterine myometrium contraction. Consequently, intervening with RAC1 represents a novel strategy for the treatment of preterm birth.

Automated summary

This study demonstrates a new functional relationship between RAC1 and uterine myometrium contraction in preterm birth, providing a novel strategy for the treatment of preterm birth.