Abstract
Adropin, a multifaceted peptide, was identified as a new metabolic hormone responsible for regulating gluco-lipid homeostasis. However, its role in the testicular function is not yet understood. We aimed to investigate the localization and expression of adropin and GPR19 during different phases of postnatal development. Immunohistochemical study revealed the intense reactivity of adropin in the Leydig cells during all phases of postnatal development, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells as well as primary and secondary spermatocytes. Western blot study revealed maximum expression of GPR19 in pre-pubertal mouse testis that clearly indicates maximum responsiveness of adropin during that period. So, we hypothesized that adropin may act as an autocrine/paracrine factor that regulates pubertal changes in mouse testis. To examine the effect of adropin on pubertal onset, we gave bilateral intra-testicular doses (0.5 and 1.5 µg/testis) to pre-pubertal mice. Adropin treatment promoted testicular testosterone synthesis by increasing the expression of StAR, 3β-HSD, and 17β-HSD. Adropin also promoted germ cell survival and proliferation by upregulating the expression of PCNA and downregulating the Bax/Bcl2 ratio and Caspase 3 expression resulting in fewer TUNEL-positive cells in adropin-treated groups. FACS analysis demonstrated that adropin treatment not only increases 1C to 4C ratio but also significantly increases the 1C (spermatid) and 1C to 2C ratio which demarcates accelerated germ cell differentiation and turnover of testicular cells. In conclusion, adropin promotes steroidogenesis, germ cell survival, as well as the proliferation in the pre-pubertal mouse testis that may hasten the pubertal transition in an autocrine/paracrine manner.
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Acknowledgements
Shashank Tripathi and Shweta Maurya highly acknowledge CSIR, New Delhi, for the grant as JRF and SRF. The DST-FIST and UGC-CAS programs of the Department of Zoology, BHU, are acknowledged. The authors are grateful to the Sophisticated Analytical and Technical Help Institute (SATHI), BHU, India for providing the flow cytometry facility.
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This work was financially supported by the Department of Science and Technology-Science and Engineering Research Board (DST-SERB) (file no. ECR/2016/001883/LS), New Delhi, India.
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The experiments were conceptualized and designed by all authors. Shashank Tripathi and Shweta Maurya conducted all the experiments and prepared graphs and figures. All authors analyzed the data. Shashank Tripathi wrote the manuscript. Ajit Singh reviewed the work and edited the final version of the manuscript. All the authors read and agreed to publish the final manuscript.
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Tripathi, S., Maurya, S. & Singh, A. Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice. Cell Tissue Res 395, 171–187 (2024). https://doi.org/10.1007/s00441-023-03852-9
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DOI: https://doi.org/10.1007/s00441-023-03852-9