| Title | Maternal exposure to PM2.5 disrupting offspring spermatogenesis through induced sertoli cells apoptosis via inhibin B hypermethylation in mice |
| Authors | Liu, Jianhui Huang, Jing Gao, Leqiang Sang, Yujian Li, Xiangyang Zhou, Guiqing Cao, Linlin Lu, Hong Zhou, Xianqing Ren, Lihua |
| Affiliation | Capital Med Univ, Beijing Obstet & Gynecol Hosp, Beijing Maternal & Child Hlth Care Hosp, Cent Lab, Beijing 100026, Peoples R China Peking Univ, Sch Nursing, Beijing 100191, Peoples R China Capital Med Univ, Sch Publ Hlth, Dept Toxicol & Hyg Chem, Beijing 100069, Peoples R China Peking Univ Third Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China Peking Univ Third Hosp, Natl Clin Res Ctr Obstet & Gynecol, Beijing, Peoples R China |
| Keywords | MALE REPRODUCTIVE TOXICITY PARTICULATE MATTER PM2.5 OXIDATIVE STRESS SEMEN QUALITY AIR-POLLUTION FERTILITY SPERM RATS |
| Issue Date | Aug-2022 |
| Publisher | ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY |
| Abstract | Particulate Matter 2.5 (PM2.5) disrupts endocrine functions and may negatively affect sperm quality and quantity in males; however, the long-term effects and potential mechanisms of this effect are unknown. This study aimed to investigate the epigenetic mechanism of maternal exposure to PM2.5-induced inhibin B hypermethylation in male offspring. In this experiment design, pregnant C57BL/6 mice were treated with two doses of PM2.5 (4.8 and 43.2 mg/kg bw). The membrane control group was given a sampling membrane and the control group received nothing. Following the formation of the vaginal plug, intratracheal instillation of PM2.5 was administered every three days until delivery of the pups. To assess the effect of PM2.5 in vitro, TM4 cells, a Sertoli-like cell line, was treated with different concentrations (0, 25, 50, 100 mu g/mL) of PM2.5 for 24 h. The results displayed that Sperm motility, as well as the number of adult offspring, was decreased in the PM2.5 exposed group relative to the untreated controls. Increased vacuolization was observed in the Sertoli cells of mice that were exposed to PM2.5 in utero. The levels of inhibin and testosterone were reduced and the levels of LH and FSH increased in the PM2.5 groups relative to the untreated controls. In vitro, PM2.5 resulted in cell cycle inhibition as well as increased apoptosis in TM4 cells. Moreover, PM2.5-induced inhibin B hypermethylation and activation of the p21/Cleaved Caspase-3 pathway resulted in TM4 cell apoptosis that was rescued through the use of a DNA methylation inhibitor. Together, our data suggest that prenatal exposure to PM2.5 results in inhibin B hypermethylation and can activate the p21/Cleaved Caspase-3 pathway, resulting in Sertoli cell apoptosis, aberrant secretion of androgen binding protein, and decreased testosterone, thus resulting in the inhibition of spermatogenesis. |
| URI | http://hdl.handle.net/20.500.11897/648412 |
| ISSN | 0147-6513 |
| DOI | 10.1016/j.ecoenv.2022.113760 |
| Indexed | SCI(E) |
| Appears in Collections: | 护理学院 第三医院 |
