Role of the kisspeptin/KISS1 receptor system in the testicular development of mice
Journal
Journal of the Chinese Medical Association
Journal Volume
84
Journal Issue
2
Pages
203-211
Date Issued
2021
Author(s)
Chiang C.-M
Chiu H.-Y
Jong D.-S
Wu L.-S
Lee Y.-J
Abstract
Background: Kisspeptin and its receptor KISS1R have been found to be essential regulators of reproductive function. Previous data have revealed the presence of Kiss1 and Kiss1r mRNAs in the hypothalamus and the testis of humans and rodents. However, the precise location and possible physiological role of the kisspeptin/KISS1R system in the testis remain ambiguous. Methods: We first produced an anti-KISS1R immunoglobulin Y antibody for KISS1R identification. To detect the exact sites of KISS1R and kisspeptin expression in the testis, we conducted immunohistochemistry assays on sections of testes. We used real-time polymerase chain reactions to identify Kiss1r in mice and to determine the expression levels of testicular genes. Finally, to verify the upstream regulation on the Kisspeptin/KISS1 receptor system, we treated primary mouse Leydig cells and MA-10 cells with luteinizing hormone (LH) and Br-cAMP, respectively, and examined Kiss1 and Kiss1r mRNA expression. Results: Immunohistochemistry assays revealed that kisspeptin was expressed in Leydig cells and KISS1R was localized in the seminiferous tubules. With real-time polymerase chain reactions, we found Kiss1r mRNA was constitutively expressed in the mouse testis from birth until the postnatal fourth week. Furthermore, mRNA expression of Kiss1 was synchronized with that of Insl3 and Cyp19a. However, the expression of the LH receptor-encoding gene increased 1 week earlier than did Kiss1 expression. This indicated that the kisspeptin/KISS1R system in the testis may be controlled by LH and cAMP signaling pathways. Finally, we confirmed that Kiss1 mRNA expression was increased in both LH-treated primary Leydig cells and Br-cAMP-treated MA-10 cells (p< 0.05). On the other hand, cotreatment of both cell lines with Br-cAMP and a protein kinase A inhibitor RP-cAMP significantly suppressed 50% of Br-cAMP-induced Kiss1 expression (p< 0.05). Conclusion: We discovered that Kiss1 expression in mouse Leydig cells was induced by LH through the cAMP/PKA pathway. Based on the presence of kisspeptin receptors on spermatids, we inferred that kisspeptin- and development-related factors have synergistic effects on spermatogenesis. Nevertheless, more studies are required to elaborate the role of the kisspeptin/KISS1R system in testicular development. ? 2020, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Subjects
aromatase; immunoglobulin Y; Kiss1 receptor; kisspeptin; luteinizing hormone; luteinizing hormone receptor; messenger RNA; steroid receptor; animal cell; animal experiment; animal tissue; antibody specificity; antibody titer; Article; cAMP signaling; cell maturation; ciliated epithelium; controlled study; enzyme linked immunosorbent assay; gene; gene expression; hypothalamus; immunocompetent cell; immunohistochemistry; insl3 gene; Leydig cell; lhcgr gene; male; molecular weight; mouse; nonhuman; oviduct; perinatal period; protein expression; protein function; protein localization; real time polymerase chain reaction; RNA extraction; seminiferous tubule; Sertoli cell; signal transduction; spermatogenesis; testis development
SDGs
Type
journal article