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ORIGINAL RESEARCH article

Front. Pediatr.
Sec. Pediatric Urology
Volume 12 - 2024 | doi: 10.3389/fped.2024.1495310

Vitamin D protects spermatogonia and Sertoli cells from heat stress damage by inhibiting NLRP3

Provisionally accepted
Han Chu Han Chu *Qi-Fei Deng Qi-Fei Deng Yuan Fang Yuan Fang
  • Anhui Provincial Children’s Hospital, Hefei, China

The final, formatted version of the article will be published soon.

    Introduction：Cryptorchidism can damage cells in the cryptorchid testes due to elevated local temperatures, potentially impacting the fertility of the child in adulthood. Research indicates that vitamin D enhances sperm quality in adult males.This study aimed to explore whether vitamin D inhibits NLRP3 activation, thus helping to mitigate heat stress damage to testicular spermatogenic and Sertoli cells.Materials and methods：Five cases of normal testicular tissue adjacent to a tumor (testis removed due to tumorous growth) and five cases of atrophied cryptorchid testicular tissue (testis removed) were analyzed for immunohistochemistry to determine NLRP3 expression in cryptorchid tissue. In Phase I, spermatogonia (GC-1) and Sertoli cells (TM4) were separated into blank and heat stress groups. Apoptosis, inflammatory factor levels, and the expression of Bcl-2 and NLRP3 genes and proteins were measured at 2, 6, and 10 hours after heat stress treatment. In Phase II, the cells were re-cultured and divided into three groups: heat stress, siRNA + heat stress, and VD + heat stress. After 10 hours, the apoptosis, inflammatory factor levels, and gene and protein expressions of Bcl-2 and NLRP3 were reassessed in each group.Phase I, extending heat stress duration led to increased apoptosis in spermatogonia (GC-1) and testicular Sertoli cells (TM4), heightened levels of inflammatory factors, reduced BCL-2 expression, and elevated NLRP3 expression compared to the control group. Phase II, both the siRNA + heat stress and VD + heat stress groups showed decreased apoptosis in spermatogonia and Sertoli cells, lower inflammatory factor levels, increased BCL-2 expression, and decreased NLRP3 expression compared to the heat stress-only group, with statistically significant differences (P < 0.05).Conclusions：This is the first time we found the expression of NLRP3 in cryptorchidism. Vitamin D can inhibit the expression of NLRP3 and reduce the damage of heat stress on testicular spermatogenic cells and Sertoli cells, and play a protective role for testicular spermatogenic cells and Sertoli cells. This provides a theoretical basis for preserving testicular function during the "treatment gap" in boys with cryptorchidism who have not received surgical treatment.

    Keywords: Cryptorchidism, Spermatogonia, Sertoli cell, Vitamin D, NLRP3

    Received: 12 Sep 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 Chu, Deng and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Han Chu, Anhui Provincial Children’s Hospital, Hefei, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.