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Published on: February 6, 2018
Short peptide perturbs spermatogenesis via immune microenvironment dysregulation and mitochondrial imbalance
Heng Wang1, Xiaofang Tan2, Deyu Chen3
1School of Basic Medical Science, Guangzhou Medical University, China.
Abstract:
A short peptide derived from the occludin protein regulates tight junctions (TJ) of the blood-testis barrier and impairs germ cell development. However, the mechanism behind how this peptide regulates TJ and induces cell apoptosis remains unclear. In the present study, an animal model with induced TJ disruption via the short peptide was used to evaluate its impact on spermatogenesis. Here, we demonstrate that the short peptide promoted the infiltration of immune cells into the testicular interstitial tissue, accompanied by upregulation expression of the pro-inflammatory factors interleukin-6 and tumor necrosis factor-α. Moreover, mitochondrial fragmentation and mitophagy were upregulated in Sertoli cells and Leydig cells. Consistently, terminal deoxynucleotidyl transferase dUTP nick end labeling staining revealed extensive apoptosis in the testes during spermatogenesis. Notably, the severity of these disruptions began to attenuate after 27 days, although full functional recovery was not observed. Our findings reveal a novel mechanism wherein peptide-induced immune dysregulation and mitochondrial dysfunction synergistically impair spermatogenesis, potentially via microenvironmental perturbation of the TJ. Overall, these findings could hold valuable insights for the development of non-hormonal male contraceptives.
Insights
A peptide disrupting the blood-testis barrier impairs sperm development by causing immune cell infiltration and mitochondrial damage. This immune dysregulation and mitochondrial dysfunction offer insights into non-hormonal male contraceptives.
Area of Science:
- Reproductive Biology
- Immunology
- Cell Biology
Background:
- Occludin-derived peptides disrupt tight junctions (TJ) of the blood-testis barrier, impacting germ cell development.
- The precise mechanisms of TJ regulation and apoptosis induction by these peptides are not fully understood.
Purpose of the Study:
- To investigate the impact of a TJ-disrupting peptide on spermatogenesis using an animal model.
- To elucidate the molecular mechanisms underlying peptide-induced impairment of germ cell development.
Main Methods:
- Utilized an animal model with induced TJ disruption via a short peptide.
- Assessed immune cell infiltration, pro-inflammatory factor expression (interleukin-6, tumor necrosis factor-α), mitochondrial morphology, mitophagy, and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining).
Main Results:
- The peptide promoted immune cell infiltration and upregulated pro-inflammatory factors in testicular tissue.
- Sertoli and Leydig cells exhibited increased mitochondrial fragmentation and mitophagy.
- Extensive apoptosis was observed in testicular germ cells during spermatogenesis.
- Disruptions showed partial attenuation after 27 days, but full recovery was not achieved.
Conclusions:
- Peptide-induced immune dysregulation and mitochondrial dysfunction synergistically impair spermatogenesis.
- These effects may occur through microenvironmental perturbation of the TJ.
- Findings suggest potential for developing non-hormonal male contraceptives.
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