2-萘胺引起的男性生殖毒性与睾丸免疫紊乱有关。
The Male Reproductive Toxicity Caused by 2-Naphthylamine Was Related to Testicular Immunity Disorders.
发表日期:2024 May 07
作者:
Pengyuan Dai, Mengqian Ding, Jingyan Yu, Yuan Gao, Miaomiao Wang, Jie Ling, Shijue Dong, Xiaoning Zhang, Xuhui Zeng, Xiaoli Sun
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
2-萘胺 (NAP) 被列为与膀胱癌相关的 I 类致癌物。日常暴露主要来自香烟和电子烟烟雾。 NAP可导致睾丸萎缩和间质组织增生;然而,NAP治疗对精子发生的影响及其相关机制尚未见报道。该研究旨在探讨持续暴露于5、20和40 mg/kg NAP 35天后,NAP对精子发生和精子生理功能的影响。我们发现,NAP(40 mg/kg)治疗组的精子活力、前向活力、精子平均路径速度和直线速度显着下降,并且NAP给药后精子变形率上升。 RNA 序列分析丰富了睾丸免疫和脂质代谢相关过程。与睾丸免疫相关的 Plvap、Ccr7、Foxn1、Trim29、Sirpb1c、Cfd 和 Lpar4 以及抑制甘油三酯和胆固醇吸收的 Pnliprp1 被证实在 NAP 暴露组中急剧上升。在 NAP 暴露组的睾丸中观察到总胆固醇和 CD68 水平增加。 Gpx5(在精子血浆中充当抗氧化剂)和 Semg1(有助于精子前向运动)均被下调。我们得出的结论是,短期暴露于 NAP 会导致生殖毒性,主要是由于睾丸炎症异常。
2-naphthylamine (NAP) was classified as a group I carcinogen associated with bladder cancer. The daily exposure is mostly from cigarette and E-cigarette smoke. NAP can lead to testicular atrophy and interstitial tissue hyperplasia; however, the outcomes of NAP treatment on spermatogenesis and the associated mechanisms have not been reported. The study aimed to investigate the effect of NAP on spermatogenesis and sperm physiologic functions after being persistently exposed to NAP at 5, 20, and 40 mg/kg for 35 days. We found that sperm motility, progressive motility, sperm average path velocity, and straight-line velocity declined remarkably in the NAP (40 mg/kg) treated group, and the sperm deformation rate rose upon NAP administration. The testis immunity- and lipid metabolism-associated processes were enriched from RNA-sequence profiling. Plvap, Ccr7, Foxn1, Trim29, Sirpb1c, Cfd, and Lpar4 involved in testis immunity and Pnliprp1 that inhibit triglyceride and cholesterol absorption were confirmed to rise dramatically in the NAP-exposed group. The increased total cholesterol and CD68 levels were observed in the testis from the NAP-exposed group. Gpx5, serving as an antioxidant in sperm plasma, and Semg1, which contributes to sperm progressive motility, were both down-regulated. We concluded that the short-term exposure to NAP caused reproductive toxicity, primarily due to the inflammatory abnormality in the testis.