Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress.

Abstract

Blood-testis barrier (BTB) damage promotes spermatogenesis dysfunction, which is a critical cause of male infertility. Dyslipidemia has been correlated with male infertility, but the major hazardous lipid and the underlying mechanism remains unclear. In this study, we firstly discovered an elevation of palmitic acid (PA) and a decrease of inhibin B in patients with severe dyszoospermia, which leaded us to explore the effects of PA on Sertoli cells. We observed a damage of BTB by PA. PA penetration to endoplasmic reticulum (ER) and its damage to ER structures were exhibited by microimaging and dynamic observation, and consequent ER stress was proved to mediate PA-induced Sertoli cell barrier disruption. Remarkably, we demonstrated a critical role of aberrant protein palmitoylation in PA-induced Sertoli cell barrier dysfunction. An ER protein, Calnexin, was screened out and was demonstrated to participate in this process, and suppression of its palmitoylation showed an ameliorating effect. We also found that ω-3 poly-unsaturated fatty acids down-regulated Calnexin palmitoylation, and alleviated BTB dysfunction. Our results indicate that dysregulated palmitoylation induced by PA plays a pivotal role in BTB disruption and subsequent spermatogenesis dysfunction, suggesting that protein palmitoylation might be therapeutically targetable in male infertility.

• Authors: Xie Ge, Zhaowanyue He, Chun Cao, Tongmin Xue, Jun Jing, Rujun Ma, Wei Zhao, Ling Liu, Kadiliya Jueraitetibaike, Jinzhao Ma, Yuming Feng, Zhang Qian, Zhichuan Zou, Li Chen, Chuanhai Fu, Ninghong Song, Bing Yao
• Journal: Redox biology (Redox Biol) Vol. 54 Pg. 102380 (08 2022) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 35803125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Calnexin
• Palmitic Acid

Topics

• Blood-Testis Barrier (metabolism)
• Calnexin (metabolism, pharmacology)
• Humans
• Infertility, Male (etiology, metabolism)
• Lipoylation
• Male
• Palmitic Acid (pharmacology)
• Spermatogenesis (physiology)