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Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats.

ABSTRACT: We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.

SUBMITTER: Santos LC

PROVIDER: S-EPMC10556046 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats.

Santos Luciano Cardoso LC Dos Anjos Cordeiro Jeane Martinha JM da Silva Santana Larissa L Barbosa Erikles Macêdo EM Santos Bianca Reis BR Mendonça Letícia Dias LD Cunha Maria Clara da Silva Galrão MCDSG Machado William Morais WM Santana Larissa Rodrigues LR Kersul Maíra Guimarães MG Henriques Patrícia Costa PC Lopes Roberta Araújo RA Snoeck Paola Pereira das Neves PPDN Szawka Raphael Escorsim RE Silva Juneo Freitas JF

Scientific reports 20231005 1

We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels ...[more]

PMID: 37798396

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Project description:Strontium (Sr) is an essential trace element in the human body and plays an important role in regulating male reproductive health. Recent studies have shown that gut flora plays a key role in maintaining spermatogenesis, as well as testicular health, through the gut-testis axis. At present, it is unclear whether gut microbiota can mediate the effects of Sr on sperm quality, and what the underlying mechanisms may be. We investigated the effects of different concentrations of strontium chloride (SrCl2) solutions (0, 50, 100, and 200 mg/kg BW) on reproductive function and gut microbiota in male Wistar rats (6-8 weeks, 250 ± 20 g). All the animals were euthanized after 37 days of treatment. The Sr-50 group significantly increased sperm concentration, sperm motility, and sperm viability in rats. After Sr treatment, serum and testicular testosterone (T) and Sr levels increased in a dose-dependent manner with increasing Sr concentration. At the same time, we also found that testicular marker enzymes (ACP, LDH) and testosterone marker genes (StAR, 3β-HSD, and Cyp11a1) increased significantly in varying degrees after Sr treatment, while serum NO levels decreased significantly in a dose-dependent manner. Further investigation of intestinal flora showed that SrCl2 affected the composition of gut microbiome, but did not affect the richness and diversity of gut microbiota. Sr treatment reduced the number of bacteria with negative effects on reproductive health, such as Bacteroidetes, Tenericutes, Romboutsia, Ruminococcaceae_UCG_014, Weissella, and Eubacterium_coprostanoligenes_group, and added bacteria with negative effects on reproductive health, such as Jeotgalicoccus. To further explore the Sr and the relationship between the gut microbiota, we conducted a Spearman correlation analysis, and the results showed that the gut microbiota was closely correlated with Sr content in serum and testicular tissue, sex hormone levels, and testicular marker enzymes. Additionally, gut microbiota can also regulate each other and jointly maintain the homeostasis of the body's internal environment. However, we found no significant correlation between intestinal flora and sperm quality in this study, which may be related to the small sample size of our 16S rDNA sequencing. In conclusion, the Sr-50 group significantly increased T levels and sperm quality, and improved the levels of testicular marker enzymes and testosterone marker genes in the rats. Sr treatment altered the gut flora of the rats. However, further analysis of the effects of gut microbiota in mediating the effects of SrCl2 on male reproductive function is needed. This study may improve the current understanding of the interaction between Sr, reproductive health, and gut microbiota, providing evidence for the development of Sr-rich foods and the prevention of male fertility decline.

Dataset Information

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats.

Publications

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats.

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