Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model.
Santos. Bianca Reis BR; Dos Anjos Cordeiro. Jeane Martinha JM; Santos. Luciano Cardoso LC; Barbosa. Erikles Macedo EM; Mendonça. Letícia Dias LD; Santos. Emilly Oliveira EO; de Macedo. Isabella Oliveira IO; de Lavor. Mário Sergio Lima MSL; Szawka. Raphael Escorsim RE; Serakides. Rogeria R; Silva. Juneo Freitas JF
Key Findings
- Daily kisspeptin‑10 raised maternal T3/T4 levels and increased fetal weight in hypothyroid rats.
- The peptide restored placental glycogen cells and increased expression of growth factors (Plgf, Igf1, Glut1).
- Kisspeptin‑10 reduced oxidative DNA damage (8‑OHdG) and boosted antioxidant enzymes (SOD1, Catalase, GPx1) in the placenta.
Practical Outcomes
- For biohackers, this suggests kisspeptin may have antioxidant and growth‑supporting effects in pregnancy, but the evidence is limited to an animal model. Until human studies are done, it’s not ready for self‑experimentation or clinical use, though it highlights a potential new avenue for supporting placental health.
Summary
In pregnant rats with low thyroid hormone, giving the peptide kisspeptin‑10 every day helped the babies grow bigger and protected the placenta from oxidative damage. The treatment boosted several growth‑factor genes and antioxidant enzymes in the placenta, but it didn’t fix all the hormone‑related changes caused by hypothyroidism.
Abstract
Maternal hypothyroidism is associated with fetal growth restriction, placental dysfunction, and reduced kisspeptin/Kiss1R at the maternal-fetal interface. Kisspeptin affects trophoblastic migration and has antioxidant and immunomodulatory activities. This study aimed to evaluate the therapeutic potential of kisspeptin in the fetal-placental dysfunction of hypothyroid Wistar rats. Hypothyroidism was induced by daily administration of propylthiouracil. Kisspeptin-10 (Kp-10) treatment was performed every other day or daily beginning on day 8 of gestation. Feto-placental development, placental histomorphometry, and expression levels of growth factors (VEGF, PLGF, IGF1, IGF2, and GLUT1), hormonal (Dio2) and inflammatory mediators (TNFα, IL10, and IL6), markers of hypoxia (HIF1α) and oxidative damage (8-OHdG), antioxidant enzymes (SOD1, Cat, and GPx1), and endoplasmic reticulum stress mediators (ATF4, GRP78, and CHOP) were evaluated on day 18 of gestation. Daily treatment with Kp-10 increased free T3 and T4 levels and improved fetal weight. Both treatments reestablished the glycogen cell population in the junctional zone. Daily treatment with Kp-10 increased the gene expression levels of <i>Plgf</i>, <i>Igf1</i>, and <i>Glut1</i> in the placenta of hypothyroid animals, in addition to blocking the increase in 8-OHdG and increasing protein and/or mRNA expression levels of SOD1, Cat, and GPx1. Daily treatment with Kp-10 did not alter the higher protein expression levels of VEGF, HIF1α, IL10, GRP78, and CHOP caused by hypothyroidism in the junctional zone compared to control, nor the lower expression of <i>Dio2</i> caused by hypothyroidism. However, in the labyrinth zone, this treatment restored the expression of VEGF and IL10 and reduced the GRP78 and CHOP immunostaining. These findings demonstrate that daily treatment with Kp-10 improves fetal development and placental morphology in hypothyroid rats, blocks placental oxidative damage, and increases the expression of growth factors and antioxidant enzymes in the placenta.
Study Information
pubmed
2022
2022-07-28T00:00:00.000Z
10.3389/fendo.2022.908240
11
100