Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model.
Santos. Luciano Cardoso LC; Dos Anjos Cordeiro. Jeane Martinha JM; Cunha. Maria Clara da Silva Galrão MCDSG; Santos. Bianca Reis BR; Oliveira. Luciana Santos de LS; da Silva. Adriana Lopes AL; Barbosa. Erikles Macêdo EM; Niella. Raquel Vieira RV; de Freitas. Gustavo José Cota GJC; Santos. Daniel de Assis DA; Serakides. Rogéria R; Ocarino. Natália de Melo NM; Borges. Stephanie Carvalho SC; de Lavor. Mário Sérgio Lima MSL; Silva. Juneo Freitas JF
Key Findings
- Hypothyroidism caused higher oxidative stress markers (TBARS, LOOH) and lower antioxidant gene expression (Sod1, Sod2, Gpx1) in rat testes.
- Kisspeptin‑10 treatment lowered testicular apoptosis and peroxynitrite levels, and boosted antioxidant enzymes (SOD1, GPX, CAT activity).
- Kisspeptin‑10 did not restore the reduced expression of unfolded protein response (UPR) genes caused by hypothyroidism.
Practical Outcomes
- For biohackers, the study hints that kisspeptin‑10 might act as an antioxidant in situations of thyroid imbalance, but the evidence is limited to rats and testicular tissue. No human dosing, safety, or delivery method is provided, so it’s not ready for direct self‑experimentation. It may be worth monitoring future research for broader metabolic or anti‑aging applications.
Summary
In rats with low thyroid hormone, giving kisspeptin‑10 helped protect the testes from oxidative damage and reduced cell death, but it didn’t fix the stress‑protein pathway that was also messed up by the thyroid problem.
Abstract
Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control (<i>n</i> = 15), Hypo (<i>n</i> = 13) and Hypo + Kp10 (<i>n</i> = 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of <i>Sod1</i>, <i>Sod2</i> and <i>Gpx1</i>, as well as the expression of <i>Grp78</i>, <i>Atf6</i>, <i>Ho1</i> and <i>Chop</i>. Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction.
Study Information
pubmed
2024
2024-01-26T00:00:00.000Z
10.3390/ijms25031514
2
74