In pregnant rats with low thyroid hormone, the placenta shows a spike in inflammatory signals that can damage cells. Giving a short kisspeptin peptide (Kp10) stopped most of that inflammation and cell‑death process, suggesting kisspeptin can calm down a specific immune pathway (NLRP3 inflammasome) in the womb.

Gestational diseases such as preeclampsia and gestational diabetes cause inflammasome activation and pyroptosis in the placenta and changes in placental kisspeptin levels. Although maternal hypothyroidism also reduces the kisspeptin/Kiss1R system at the maternal-fetal interface, there is still no information on whether this dysfunction causes inflammasome activation and pyroptosis in the placenta or influences the modulatory role of kisspeptin in these processes. This study aimed to evaluate whether hypothyroidism activates the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and whether kisspeptin can modulate these processes. Hypothyroidism was induced in Wistar rats by the administration of propylthiouracil. Kisspeptin-10 (Kp10) treatment began on the 8th day of gestation (DG). Gene and/or protein expressions of NLRP3, Caspase 1, IL-1&#x3b2;, IL-18, and Gasdermin D (Gsmd) were evaluated in the deciduae and placentae at the 18th DG. Hypothyroidism increased the decidual and placental stainings of NLRP3, IL-1&#x3b2;, and Gasdermin D, and increased the gene expressions of <i>Nlrp3</i>, <i>Il&#x3b2;</i>, and <i>Il18</i> in the placenta and of <i>Gsmd</i> in the decidua. Treatment with Kp10 suppressed the increase in NLRP3/<i>Nlrp3</i>, IL-1&#x3b2;, <i>Il18</i>, and Gasdermin D/<i>Gsmd</i> caused by hypothyroidism at the maternal-fetal interface. However, Kp10 increased the placental gene expressions of <i>Casp1</i> and <i>Il1&#x3b2;</i>. The findings demonstrated that maternal hypothyroidism activated the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and that treatment with Kp10 was able to block these processes, thus suggesting that kisspeptin analogues may be promising in the treatment of gestational diseases that involve inflammasome activation and pyroptosis.