Adropin promotes testicular functions by modulating redox homeostasis in adult mouse.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2024-10-01 Epub Date: 2024-06-15 DOI:10.1007/s12020-024-03921-1

Shashank Tripathi, Shweta Maurya, Ajit Singh

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引用次数: 0

Abstract

Purpose: Adropin is an emerging metabolic hormone that has a role in regulating energy homeostasis. The present study aimed to explore the impact of adropin on redox homeostasis and its possible role in testicular functions in adult mouse testis.

Methods: Western blot, flow-cytometry, and TUNEL assay were performed to explore the impact of intra-testicular treatment of adropin (0.5 μg/testis) on testicular functions of adult mice. Hormonal assay was done by ELISA. Further, antioxidant enzyme activities were measured.

Results: Adropin treatment significantly increased the sperm count and testicular testosterone by increasing the expression of GPR19 and steroidogenic proteins. Also, adropin treatment reduced the oxidative/nitrosative stress by facilitating the translocation of NRF2 and inhibiting NF-κB into the nucleus of germ cells. Enhanced nuclear translocation of NRF2 leads to elevated biosynthesis of antioxidant enzymes, evident by increased HO-1, SOD, and catalase activity that ultimately resulted into declined LPO levels in adropin-treated mice testes. Furthermore, adropin decreased nuclear translocation of NF-κB in germ cells, that resulted into decreased NO production leading to decreased nitrosative stress. Adropin/GPR19 signaling significantly increased its differentiation, proliferation, and survival of germ cells by elevating the expression of PCNA and declining caspase 3, cleaved caspase 3 expression, Bax/Bcl2 ratio, and TUNEL-positive cells. FACS analysis revealed that adropin treatment enhances overall turnover of testicular cells leading to rise in production of advanced germ cells, notably spermatids.

Conclusion: The present study indicated that adropin improves testicular steroidogenesis, spermatogenesis via modulating redox potential and could be a promising target for treating testicular dysfunctions.

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阿托品通过调节成年小鼠的氧化还原稳态促进睾丸功能

目的：阿糖腺苷是一种新兴的代谢激素，在调节能量平衡方面发挥作用。本研究旨在探讨阿托品对氧化还原稳态的影响及其在成年小鼠睾丸功能中可能发挥的作用：方法：通过Western印迹、流式细胞术和TUNEL检测，探讨阿托品（0.5 μg/睾丸）睾丸内处理对成年小鼠睾丸功能的影响。激素测定采用酶联免疫吸附法。此外，还测定了抗氧化酶活性：结果：通过增加 GPR19 和类固醇生成蛋白的表达，阿托品能明显增加精子数量和睾丸睾酮。此外，阿托品还能促进 NRF2 转位并抑制 NF-κB 进入生殖细胞核，从而减少氧化/亚硝酸应激。NRF2的核转位增强会导致抗氧化酶的生物合成增加，HO-1、SOD和过氧化氢酶活性的增加就证明了这一点，最终导致阿托品处理的小鼠睾丸中LPO水平下降。此外，阿托品还减少了生殖细胞中 NF-κB 的核转位，从而减少了 NO 的产生，降低了亚硝基应激。阿托品/GPR19信号通过提高PCNA的表达，降低caspase 3、裂解caspase 3的表达、Bax/Bcl2比率和TUNEL阳性细胞，从而显著提高生殖细胞的分化、增殖和存活率。FACS分析表明，阿托品治疗可促进睾丸细胞的整体更替，导致高级生殖细胞（尤其是精母细胞）的生成增加：本研究表明，阿托品可通过调节氧化还原电位改善睾丸类固醇生成和精子生成，可能是治疗睾丸功能障碍的一个有前途的靶点。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.