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

  • Mahsa Yaghobinejad (Anatomy Department, Medical School, Tehran University of Medical Science) ;
  • Heidar Toolee (School of Allied Medical Sciences, Shahrud University of Medical Sciences) ;
  • Somayeh Solhjoo (Anatomy Department, Medical School, Kerman University of Medical Science) ;
  • Elham Seifali (Anatomy Department, Azad Islamic University of Medical Science) ;
  • Soraya Parvari (Anatomy Department, School of Medicine, Alborz University of Medical Science) ;
  • Omotosho Dhulqarnain Akanji (Anatomy Department, Olabisi Onabanjo University) ;
  • Tayebeh Rastegar (Anatomy Department, Medical School, Tehran University of Medical Science)
  • Received : 2023.11.05
  • Accepted : 2024.01.17
  • Published : 2024.12.31

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 GPR-C6A, 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.

Keywords

Acknowledgement

We would like to thank staff of Anatomical Department for their support.

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