Virtual Presentation SRB Virtual Awards 2020

Mechanisms involved with female reproductive disorders caused by hypothyroidism and promising therapeutic targets (#20)

Juneo F Silva 1
  1. Department of Biological Sciences, State University of Santa Cruz, Ilheus, Bahia, Brazil.

Hypothyroidism is one of the main endocrinopathies causing reproductive dysfunctions in women and animals. Hypothyroidism affects the gonadal and placental morphophysiology and reduces the release of luteinizing hormone (LH), which are associated with infertility and decreased hypothalamic expression of kisspeptin (Kp), a key neuropeptide in reproduction. Using a combination of in vivo and in vitro models, we have previously shown that hypothyroidism affects the luteal function and the differentiation and angiogenic, hormonal, and immune activity of trophoblastic cells, compromising cyclicity, fetal-placental growth, and intrauterine trophoblast migration. Hypothyroidism affects the anti-inflammatory environment at the maternal-fetal interface that is necessary to prevent fetal rejection, in addition to affecting the placental expression of Kp. These findings are similar to those for the placenta of women and animal models with preeclampsia and gestational diabetes, suggesting that the reproductive changes caused by hypothyroidism can be a result of oxidative stress and failure in the peripheral expression of Kp. Therefore, my research aims to i) evaluate the role of cellular stress and kisspeptin in the context of reproductive changes caused by metabolic diseases; ii) study the pathogenesis of metabolic placental dysfunctions; and iii) identify possible therapeutic strategies for metabolic reproductive disorders. Our recent results have shown that treatment with Kp, owing to its central role in LH release and antioxidant action, was able to restore the ovarian and testicular function of hypothyroid rats and improve sperm activity, in addition to improving fetal development in maternal hypothyroidism. Manganese porphyrins, which have high antioxidant potential, are also able to prevent the occurrence of oxidative stress and endoplasmic reticulum stress in the placenta of hypothyroid rats, improving fetal growth. These findings reveal novel mechanisms involved in gonadal and placental dysfunction caused by hypothyroidism and suggest possible alternative therapeutic approaches to improve fertility in hypothyroid patients.