Kisspeptin Restores Placental mTOR Signaling and Improves Glucose Homeostasis Mediators Disrupted by Maternal Hypothyroidism in Rats.

AIM: Reduced placental mTOR signaling is associated with intrauterine growth restriction and impaired maternal and placental metabolism. Since maternal hypothyroidism induces intrauterine growth restriction, and maternal treatment with kisspeptin-10 (Kp10) has been shown to improve feto-placental development in hypothyroid rats, this study aimed to evaluate the effects of maternal hypothyroidism, with and without kisspeptin-10 treatment, on maternal energy homeostasis and placental expression of mTOR and glucose metabolism mediators.

METHODS

Maternal hypothyroidism was induced by administration of propylthiouracil, and kisspeptin-10 treatment began on gestational day 8.

RESULTS

Maternal hypothyroidism caused glucose intolerance, decreased insulin and HDL levels, reduced fetal and placental weights, and thinned the placental interhaemal barrier. It also increased INSRβ and AKT, while downregulating placental p-mTOR/mTOR and Glut1. Although kisspeptin-10 treatment did not improve maternal glucose homeostasis or prevent feto-placental growth restriction, it attenuated maternal hypothyroidism-induced placental Glut1 dysregulation, upregulated the IGF1/IGF1R axis, and restored placental AKT/mTOR expression.

CONCLUSION

These findings suggest that kisspeptin-10 treatment in hypothyroid pregnant rats improves placental mTOR signaling and glucose metabolism mediators, highlighting novel pathways through which kisspeptin may modulate placental physiology.