Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's, Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Toxicol Appl Pharmacol. 2022 Jul 15;447:116069. doi: 10.1016/j.taap.2022.116069. Epub 2022 May 20.
Bisphenol AF (BPAF) is one of the primary alternatives of bisphenol A. It has been ubiquitously detected in the environment and is an emerging endocrine disrupting compound. However, the effects of BPAF exposure on fetal Leydig cells and germ cells and the underlying mechanisms remain largely unknown. To this end, pregnant Sprague-Dawley rats were exposed to 10, 50, and 200 mg/kg/d BPAF by gavage from gestational days 14 to 21. The neonatal rats were sacrificed on day 1 at birth. The results showed that serum testosterone levels were significantly decreased at 50 and 200 mg/kg/d, the expression of Scarb1, Star, Cyp17a1, Hsd17b3, and Dhh and their proteins were markedly down-regulated at 50 and 100 mg/kg/d. BPAF exposure also significantly increased the incidence of multinucleated gonocytes at 200 mg/kg/d. We further detected significant increase of testicular malondialdehyde levels and reduction of antioxidants, including SOD1, SOD2, and CAT at 50 and/or 200 mg/kg/d. Furthermore, BPAF markedly reduced the levels of SIRT1 and PGC1α at 200 mg/kg/d while significantly increased AMPK phosphorylation in the testes at 50 and 200 mg/kg/d. In conclusion, our results provide novel in vivo data that BPAF can induce fetal Leydig cell dysfunction by interfering with steroidogenic networks and induce the formation of multinucleated gonocytes after suppressing the antioxidant defense system and reducing SIRT1 and PGC1α signals and increasing the phosphorylation of AMPK, which highlights the potential health risk of environmental exposure to BPAF in inducing male reproductive tract malformation.
双酚 AF（BPAF）是双酚 A 的主要替代品之一。它已在环境中广泛存在，是一种新兴的内分泌干扰化合物。然而，BPAF 暴露对胎儿睾丸间质细胞和生殖细胞的影响及其潜在机制在很大程度上仍不清楚。为此，将怀孕的 Sprague-Dawley 大鼠通过灌胃从妊娠第 14 天到第 21 天暴露于 10、50 和 200mg/kg/d 的 BPAF。新生大鼠在出生第 1 天被处死。结果表明，血清睾酮水平在 50 和 200mg/kg/d 时显著降低，Scarb1、Star、Cyp17a1、Hsd17b3 和 Dhh 的表达及其蛋白在 50 和 100mg/kg/d 时明显下调。BPAF 暴露还显著增加了 200mg/kg/d 时多核性精原细胞的发生率。我们进一步检测到，在 50 和/或 200mg/kg/d 时，睾丸丙二醛水平显著升高，抗氧化剂包括 SOD1、SOD2 和 CAT 减少。此外，BPAF 在 200mg/kg/d 时明显降低了 SIRT1 和 PGC1α 的水平，而在 50 和 200mg/kg/d 时明显增加了睾丸中 AMPK 的磷酸化。总之，我们的研究结果提供了新的体内数据，表明 BPAF 可以通过干扰类固醇生成网络来诱导胎儿睾丸间质细胞功能障碍，并在抑制抗氧化防御系统、降低 SIRT1 和 PGC1α 信号、增加 AMPK 磷酸化后诱导多核性精原细胞形成，这凸显了环境暴露于 BPAF 对男性生殖道畸形的潜在健康风险。
