Nicotinamide counteracts endothelin-1's detrimental effect on uterine decidualization during early pregnancy by influencing EDNRB

Endothelin-1 is involved in pathogenesis of preeclampsia. Mice (Edn1H/+) having excess endothelin-1developed preeclampsia-like phenotypes during pregnancy in a maternal genotype-dependent manner. Here, we investigate whether decidualization is impaired in Edn1H/+ dams, and whether nicotinamide (a potent inhibitor of endothelin-1) executes any beneficial effect. We compared implantation sites between wild type (WT) and Edn1H/+ dams with or without nicotinamide treatment. Implantation sites of Edn1H/+ dams exhibited abnormal ectoplacental cone and sinusoids with reduced vascular density in mesometrial regions of deciduae. There was more VEGF expression in decidua of Edn1H/+ dams than WT dams. The markers of decidualization were decreased in Edn1H/+ dams. Nicotinamide corrected the abnormality in Edn1H/+ dams. During differentiation (decidualization) of cultured human endometrial stomal cells, endothelin-1 halved the upregulated expression of markers of decidualization. Nicotinamide normalizes their expression. Nicotinamide counteracts ET-1's detrimental effects on endometrial decidualization. It has potential to improve embryo implantation and subsequent pregnancy outcomes. Overall design: a unilateral renal IRI model was established in wild-type (WT) and ELMO1-overexpressing (Elmo1 H/H) mice.