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骨钙素可改善无精子症小鼠的睾丸形态,但不能改善其睾酮合成信号通路。

Osteocalcin improves testicular morphology but does not ameliorate testosterone synthesis signaling in azoospermic mice.

作者信息

Yaghobinejad Mahsa, Toolee Heidar, Solhjoo Somayeh, Seifali Elham, Parvari Soraya, Akanji Omotosho Dhulqarnain, Rastegar Tayebeh

机构信息

Anatomy Department, Medical School, Tehran University of Medical Science, Tehran, Iran.

School of Allied Medical Sciences, Shahrud University of Medical Sciences, Shahrud, Iran.

出版信息

Clin Exp Reprod Med. 2024 Dec;51(4):344-352. doi: 10.5653/cerm.2023.06674. Epub 2024 Jun 10.

Abstract

OBJECTIVE

Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G protein-coupled receptor class C group 6 member A (GPRC6A) on Leydig cells and with androgen receptors on Sertoli cells.

METHODS

Adult mice were assigned to the following groups: control; sham I, which received dimethyl sulfoxide for 5 weeks followed by phosphate-buffered saline for 1 month; azoospermia, which was treated with busulfan (40 mg/kg); sham II, which consisted of azoospermic animals that received phosphate-buffered saline for 1 month beginning at the 5-week mark; and the experimental group, which included azoospermic mice treated with OCN (3 ng/g/day) for 1 month.

RESULTS

In the mice receiving OCN treatment, immunohistochemical analysis revealed increased expression of androgen receptors and GPRC6A, indicative of enhanced spermatogenesis. Additionally, the expression levels of the cyclic adenosine monophosphate-responsive element binding protein 1, steroidogenic acute regulatory protein, and cytochrome P450 family 11 genes were elevated. However, testosterone levels exhibited no significant differences across groups. Morphometric analysis suggests that OCN may play a crucial role in spermatogenesis, as evidenced by its positive effects on germinal cells and the germinal epithelium in the azoospermia group (p<0.05).

CONCLUSION

We conclude that OCN may serve as a beneficial therapeutic agent for male infertility.

摘要

目的

骨钙素(OCN)与睾酮和雌激素共同影响精子发生。OCN通过与睾丸间质细胞上的G蛋白偶联受体C类第6组成员A(GPRC6A)以及支持细胞上的雄激素受体结合,促进睾酮的分泌。

方法

将成年小鼠分为以下几组:对照组;假手术I组,接受5周二甲亚砜治疗,随后1个月接受磷酸盐缓冲盐水;无精子症组,用白消安(40 mg/kg)治疗;假手术II组,由无精子症动物组成,从第5周开始接受1个月的磷酸盐缓冲盐水;实验组,包括用OCN(3 ng/g/天)治疗1个月的无精子症小鼠。

结果

在接受OCN治疗的小鼠中,免疫组织化学分析显示雄激素受体和GPRC6A的表达增加,表明精子发生增强。此外,环磷酸腺苷反应元件结合蛋白1、类固醇生成急性调节蛋白和细胞色素P450家族11基因的表达水平升高。然而,各组之间的睾酮水平没有显著差异。形态计量学分析表明,OCN可能在精子发生中起关键作用,无精子症组中其对生殖细胞和生精上皮的积极作用证明了这一点(p<0.05)。

结论

我们得出结论,OCN可能作为男性不育症的一种有益治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9371/11617912/2e3623b79831/cerm-2023-06674f1.jpg

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