Apelin receptor antagonist (ML221) treatment has a stimulatory effect on the testicular proliferation, antioxidants system and steroidogenesis in adult mice

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2023-10-01 DOI:10.1016/j.npep.2023.102354

Milirani Das, Guruswami Gurusubramanian, Vikas Kumar Roy

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Abstract

The expression of apelin and its receptor (APJ) has been shown in the hypothalamus-pituitary-testicular axis. It has also been suggested apelin and APJ are neuropeptide factors. The presence of apelin and APJ in the seminiferous tubules and interstitium might be predicted to act as a local regulator of testicular activity, although the function is not well known in the mice testis. In the present study, we have investigated the effects of APJ, antagonist, ML221 on the gonadotropin levels, testicular steroidogenesis, proliferation, apoptosis and antioxidant system. Our results showed that inhibition of APJ by ML221 increased the sperm concentration, circulating testosterone, FSH, LH levels and intra-testicular testosterone concentration. Furthermore, ML221 treatment stimulates the germ cell proliferation and antioxidant system in the testis. The expression of BCL2, AR was up-regulated whereas, the expression of BAX and active caspase3 was down-regulated after ML221 treatment. Immunohistocehmical analysis of AR also showed increase abundance in the spermatogonia, primary spermatocytes and Leydig cells of 150 μg/kg dose group. These findings suggest that in adult testis, the apelin system might have an inhibitory role in germ cell proliferation and a stimulatory role in apoptosis. It might also be suggested that the apelin system could be involved in the disposal mechanism for damaged germ cells during spermatogenesis via the down-regulation of AR.

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Apelin受体拮抗剂(ML221)对成年小鼠睾丸增生、抗氧化系统和甾体生成具有刺激作用

apelin及其受体（APJ）在下丘脑-垂体-睾丸轴中的表达已得到证实。也有人认为apelin和APJ是神经肽因子。曲精小管和间质中apelin和APJ的存在可能被预测为睾丸活动的局部调节因子，尽管其功能在小鼠睾丸中尚不清楚。在本研究中，我们研究了APJ、拮抗剂ML221对促性腺激素水平、睾丸类固醇生成、增殖、细胞凋亡和抗氧化系统的影响。我们的结果表明，ML221对APJ的抑制增加了精子浓度、循环睾酮、FSH、LH水平和睾丸内睾酮浓度。此外，ML221处理刺激睾丸中的生殖细胞增殖和抗氧化系统。ML221处理后，BCL2、AR的表达上调，而BAX和活性caspase3的表达下调。AR的免疫组织化学分析还显示，150μg/kg剂量组的精原细胞、初级精母细胞和Leydig细胞的丰度增加。这些发现表明，在成年睾丸中，apelin系统可能在生殖细胞增殖中起抑制作用，在细胞凋亡中起刺激作用。这也可能表明apelin系统可能通过下调AR参与精子发生过程中受损生殖细胞的处理机制。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.