Transforming Growth Factor-beta 1 Alleviates Uterine Bleeding after Medication Abortion in Early Pregnancy by Upregulating the p53/Plasminogen Activator Inhibitor-1 Pathway

Abstract

TGF-β1 plays a significant role in pregnancy outcomes. This research sought to investigate whether TGF-β1 is involved in the bleeding mechanism after medication abortion (MA) in early pregnancy. The MA rat model was established in vivo using mifepristone and misoprostol, and trophoblasts HTR8/SVneo were treated with lipopolysaccharide in vitro. Changes in uterine morphology, weight, and bleeding were assessed. tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), estradiol, and progesterone levels were detected by ELISA. HE staining was employed to analyze uterine pathological changes. Apoptosis was assessed by TUNEL staining. Inflammatory cytokine expression was assessed by ELISA and qRT-PCR. Related protein levels were analyzed by Western blot. MA induction led to abnormal uterine morphology, reduced uterine weight, and heavier bleeding. MA rats showed higher tPA, uPA, IL-6, and TNF-α levels, and lower estradiol and progesterone levels compared to controls. Moreover, trophoblast tissue damage with excessive apoptosis was observed in MA rats. TGF-β1, p53, and PAI-1 levels were markedly decreased after MA induction. In HTR8/SVneo cells, lipopolysaccharide treatment significantly inhibited cellular functions, reduced TGF-β1, p53, and PAI-1 levels, and increased IL-6 and TNF-α levels. Notably, these changes were partially reversed by overexpression of TGFB1. In conclusion, TGF-β1 protects trophoblasts and alleviates MA-induced uterine bleeding by upregulating the p53/PAI-1 pathway.