College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China.
Reprod Toxicol. 2022 Jun;110:161-171. doi: 10.1016/j.reprotox.2022.04.007. Epub 2022 Apr 30.
The compound 3-methylcholanthrene (3-MC) is an environmental pollutant belonging to the PAHs, which reportedly have the potential to disrupt the endocrine systems of animals. In the present study, 4-week-old male and female mice were given 3-MC through their diet at a dose of 0.5 mg/kg of chow for 6 weeks before pregnancy. The first filial (F) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 or 10 weeks (F-5 W or F-10 W), and the potential effects on the F and F offspring were evaluated. The results showed that the serum and testicular testosterone (T) levels and the genes involved in T synthesis in F males and male F-5 W individuals born from female mice exposed to 3-MC were significantly decreased. In addition, histological analysis suggested that exposure to 3-MC significantly disrupted testicular morphology in F mice and in the offspring of female mice exposed to 3-MC. Further investigation revealed that genes involved in spermatogenesis, such as Phosphoglycerate kinase 2 (Pgk2), Glial cell derived neurotrophic factor (Gdnf), Myeloblastosis oncogene (Myb), DEAD box helicase 4 (Ddx4) and KIT proto-oncogene receptor tyrosine kinase (Kit), were suppressed in these mice. However, the adverse effects of parental 3-MC exposure on the adolescent mice were mitigated when they grew to adulthood, which was verified by studies on F-10 W mice. Our results suggest that female exposure to 3-MC has the potential to disrupt the endocrine system and spermatogenesis in male offspring; nevertheless, the adverse effects might be mitigated with age.
3-甲基胆蒽（3-MC）是一种环境污染物，属于多环芳烃（PAHs），据报道，它有可能破坏动物的内分泌系统。在本研究中，将 4 周龄雄性和雌性小鼠用含 0.5mg/kg 3-MC 的饲料进行为期 6 周的处理，然后进行妊娠。暴露或未暴露于亲代母鼠的第一代（F）后代在 5 或 10 周龄（F-5W 或 F-10W）时被处死，并评估其对 F 和 F 后代的潜在影响。结果表明，暴露于 3-MC 的雄性 F 代及其母鼠暴露后代雄性 F-5W 的血清和睾丸睾酮（T）水平以及 T 合成相关基因显著降低。此外，组织学分析表明，3-MC 暴露显著破坏了 F 代小鼠和母鼠暴露后代的睾丸形态。进一步的研究表明，参与精子发生的基因，如磷酸甘油酸激酶 2（Pgk2）、胶质细胞源性神经营养因子（Gdnf）、髓细胞瘤癌基因（Myb）、DEAD 盒解旋酶 4（Ddx4）和 KIT 原癌基因受体酪氨酸激酶（Kit），在这些小鼠中受到抑制。然而，当 F-10W 代小鼠成年后，亲代 3-MC 暴露对青少年小鼠的不良影响得到缓解。我们的结果表明，母体暴露于 3-MC 可能破坏雄性后代的内分泌系统和精子发生；然而，随着年龄的增长，这种不利影响可能会减轻。
