The anti-inflammatory effect of the amniotic PPARγ pathways is not dysregulated by the alternative plasticizer DINCH and its metabolite MINCH in human fetal membranes.

Abstract

Plasticizers, particularly phthalates, are widely used to enhance the properties of plastics, yet their harmful effects on human health, especially reproductive health, have raised concerns. This has led governments to promote the use of non-phthalate substitutes. Preterm premature rupture of fetal membranes (PPROM), affecting 3-4% of pregnancies and contributing to 40-50% of preterm births worldwide, has been associated with traditional phthalate exposure. However, no clear link has yet been established between alternative plasticizers and preterm births. Among these substitutes, DINCH (used as a phthalate replacement) and its metabolite, MINCH, appear to be promising options, although their health impacts remain largely unexplored. This study aims to assess the potential effects of DINCH and MINCH on the physiology of fetal membranes, focusing on the nuclear receptor PPARγ, which plays a critical role in pregnancy maintenance. An amniotic epithelial cell model was used to evaluate DINCH and MINCH influence on cytotoxicity, cell viability, and PPARγ activity, including its anti-inflammatory properties. Both exhibited no cytotoxic effects, did not alter PPARγ expression, and did not affect its anti-inflammatory properties. These findings suggest that DINCH and MINCH could serve as safe alternatives to phthalates, potentially reducing the risk of weakening and premature rupture of fetal membranes.