Preterm birth (PTB) remains a challenging issue in the reproductive field, and cervical maturation is an essential physiological prerequisite for parturition. The cervix is rich in smooth muscle cells, and their abnormal contractility is a key trigger for premature cervical remodeling, which may further lead to spontaneous PTB. Herein, we found that high serum arachidonic acid (AA) expression in PTB mice may predict potential harms through untargeted metabolomics analysis. After AA intervention, immunofluorescence/qPCR/WB revealed that the expression of cervical smooth muscle contraction indexes calponin/oxytocin receptor (OR)/connexin-34 and premature birth-related factors cyclooxygenase-2 (COX-2) increased significantly, indicating that AA acting on cervical smooth muscle cells may lead to premature birth. WB results showed that the expression of phosphorylated myosin light chain (p-MLC) in cervical smooth muscle cells treated with AA increased significantly, and myosin light chain (MLC) protein was closely related to smooth muscle contraction. After adding the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway inhibitor, the expression of p-MLC decreased significantly, indicating that AA could induce MLC phosphorylation through the RhoA/ROCK signaling pathway to cause cervical smooth muscle shrinkage and lead to premature birth. In summary, our findings provided evidence that AA enhanced cervical smooth muscle contraction and led to PTB by inducing MLC phosphorylation through the RhoA/ROCK signaling pathway. Hence, our study provided new insights into mechanisms linking cervical smooth muscle contraction to PTB muscle shrinkage, suggesting that AA could be a potential novel drug intervention target for PTB therapy.
Chen et al. (Thu,) studied this question.