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去负荷诱导成年雄性大鼠下丘脑 Kiss-1 表达下调导致生殖抑制。

Hindlimb unloading-induced reproductive suppression via Downregulation of hypothalamic Kiss-1 expression in adult male rats.

机构信息

Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.

出版信息

Reprod Biol Endocrinol. 2021 Mar 4;19(1):37. doi: 10.1186/s12958-021-00694-4.

DOI:10.1186/s12958-021-00694-4
PMID:33663539
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7931529/
Abstract

BACKGROUND

Spaceflights-induced microgravity can alter various physiological processes in human's body including the functional status of the reproductive system. Rodent model of tail-suspension hindlimb unloading is extensively used to stimulate the organs responses to the microgravity condition. This study explores the potential effects of hindlimb unloading on testicular functions and spermatogenesis in adult male rats and the underlying mechanism/s.

METHODS

Twenty Sprague-Dawley rats were allotted into two groups: normally loaded group (control; all arms were in touch with the grid floor) and hindlimb unloaded group (HU; only the forearms were in contact with the grid floor).

RESULTS

Following 30 days of exposure, the HU group saw a decline in body weight, testicular and epidydimal weights, and all semen parameters. The circulating concentrations of gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone significantly decreased, while levels of kisspeptin, corticosterone, inhibin, prolactin and estradiol (E2) increased in the HU group. Intratesticular levels of 5α-reductase enzyme and dihydrotestosterone (DHT) were suppressed, while the levels of aromatase and kisspeptin were significantly elevated in the HU group. Hypothalamic kisspeptin (Kiss1) mRNA expression levels were downregulated while its receptors (Kiss1R) were upregulated in the HU group. On the contrary, the mRNA expression levels of testicular Kiss1 were upregulated while Kiss1R were downregulated. The pituitary mRNA expression levels of FSHβ and LHβ decreased in the HU group. The levels of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and nitric oxide (NO) concentrations, and total antioxidant capacity (TAC) were elevated while malondialdehyde (MDA) concentrations declined in the testes of HU group. The testes of the HU rats showed positive immunostaining of caspase-3, heat shock protein 70 (HSP70) and Bcl2.

CONCLUSIONS

Altogether, these results revealed an inhibitory effect of hindlimb unloading on kisspeptin signaling in the hypothalamic-pituitary-testicular axis with impaired spermatogenesis and steroidogenesis.

摘要

背景

航天飞行引起的微重力会改变人体的各种生理过程,包括生殖系统的功能状态。鼠尾部悬吊后肢去负荷模型被广泛用于刺激器官对微重力条件的反应。本研究探讨了后肢去负荷对成年雄性大鼠睾丸功能和精子发生的潜在影响及其潜在机制。

方法

将 20 只 Sprague-Dawley 大鼠分为两组:正常负荷组(对照组;所有手臂均接触网格地板)和后肢去负荷组(HU 组;仅前肢接触网格地板)。

结果

暴露 30 天后,HU 组体重、睾丸和附睾重量以及所有精液参数均下降。促性腺激素释放激素(GnRH)、卵泡刺激素(FSH)、黄体生成素(LH)和睾酮的循环浓度显著降低,而 kisspeptin、皮质酮、抑制素、催乳素和雌二醇(E2)的水平在 HU 组升高。睾丸内 5α-还原酶和二氢睾酮(DHT)水平受到抑制,而芳香化酶和 kisspeptin 水平在 HU 组显著升高。下丘脑 kisspeptin(Kiss1)mRNA 表达水平下调,而 HU 组 kisspeptin 受体(Kiss1R)上调。相反,睾丸内 Kiss1 的 mRNA 表达水平上调,而 Kiss1R 下调。HU 组垂体 FSHβ和 LHβ 的 mRNA 表达水平降低。睾丸中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和一氧化氮(NO)浓度的抗氧化酶水平以及总抗氧化能力(TAC)升高,而丙二醛(MDA)浓度降低。HU 组大鼠睾丸 caspase-3、热休克蛋白 70(HSP70)和 Bcl2 呈阳性免疫染色。

结论

综上所述,这些结果表明,后肢去负荷对下丘脑-垂体-睾丸轴中的 kisspeptin 信号具有抑制作用,导致精子发生和类固醇生成受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/97843e92d47c/12958_2021_694_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/97843e92d47c/12958_2021_694_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/e77b88f02c71/12958_2021_694_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/4fd84e2e2760/12958_2021_694_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/55e7c5ce87a6/12958_2021_694_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/e867ea799671/12958_2021_694_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/6f4713007198/12958_2021_694_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/1687257742ef/12958_2021_694_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b739/7931529/97843e92d47c/12958_2021_694_Fig9_HTML.jpg

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