Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats

Abstract

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-1β, 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-1β, and Gasdermin D, and increased the gene expressions of Nlrp3, Ilβ, and Il18 in the placenta and of Gsmd in the decidua. Treatment with Kp10 suppressed the increase in NLRP3/Nlrp3, IL-1β, Il18, and Gasdermin D/Gsmd caused by hypothyroidism at the maternal-fetal interface. However, Kp10 increased the placental gene expressions of Casp1 and Il1β. 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.

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Comparison of solvent systems on extraction, quality characteristics, and volatile compounds of palm kernel oil

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Placental Related Disorders of Pregnancy 2.0

“…This is followed by detailed reviews of the apelinergic system in pregnancy [ 4 ]; serum screen markers for trisomy 21 and the crucial involvement of the placenta [ 5 ]; how the placenta can provide a protective role in SARS-CoV-2 transplacental transmission [ 6 ]; endoplasmic reticulum aminopeptidase 1 and 2 and their involvement in pregnancy and cancer [ 7 ]; and how rodent and rabbit models can be used in pre-eclampsia research [ 8 ]. Moreover, this Special Issue also contains original articles with novel data covering hypothyroidism [ 9 ] and pre-eclampsia/fetal growth restriction [ 10 , 11 , 12 , 13 ].…”