School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Environ Res. 2024 Jun 1;250:118485. doi: 10.1016/j.envres.2024.118485. Epub 2024 Feb 17.
Per- and polyfluoroalkyl substances (PFAS) have already drawn a lot of attention for their accumulation and reproductive toxicity in organisms. Perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), two representative PFAS, are toxic to humans and animals. Due to their widespread use in environmental media with multiple toxicities, PFOA and PFOS have been banned in numerous countries, and many substitutes have been produced to meet market requirements. Unfortunately, most alternatives to PFOA and PFOS have proven to be cumulative and highly toxic. Of the reported multiple organ toxicities, reproductive toxicity deserves special attention. It has been confirmed through epidemiological studies that PFOS and PFOA are not only associated with reduced testosterone levels in humans, but also with an association with damage to the integrity of the blood testicular barrier. In addition, for women, PFOA and PFOS are correlated with abnormal sex hormone levels, and increase the risk of infertility and abnormal menstrual cycle. Nevertheless, there is controversial evidence on the epidemiological relationship that exists between PFOA and PFOS as well as sperm quality and reproductive hormones, while the evidence from animal studies is relatively consistent. Based on the published papers, the potential toxicity mechanisms for PFOA, PFOS and their substitutes were reviewed. For males, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Apoptosis and autophagy in spermatogenic cells; (2) Apoptosis and differentiation disorders of Leydig cells; (3) Oxidative stress in sperm and disturbance of Ca channels in sperm membrane; (4) Degradation of delicate intercellular junctions between Sertoli cells; (5) Activation of brain nuclei and shift of hypothalamic metabolome. For females, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Damage to oocytes through oxidative stress; (2) Inhibition of corpus luteum function; (3) Inhibition of steroid hormone synthesis; (4) Damage to follicles by affecting gap junction intercellular communication (GJIC); (5) Inhibition of placental function. Besides, PFAS substitutes show similar reproductive toxicity with PFOA and PFOS, and are even more toxic to the placenta. Finally, based on the existing knowledge, future developments and direction of efforts in this field are suggested.
全氟和多氟烷基物质（PFAS）因其在生物体内的积累和生殖毒性而备受关注。全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）是两种具有代表性的 PFAS，对人类和动物具有毒性。由于它们广泛应用于具有多种毒性的环境介质中，因此已在许多国家被禁止使用，并且已经生产了许多替代品以满足市场需求。不幸的是，大多数 PFOA 和 PFOS 的替代品已被证明具有蓄积性和高度毒性。在所报道的多种器官毒性中，生殖毒性值得特别关注。通过流行病学研究已经证实，PFOS 和 PFOA 不仅与人类睾丸酮水平降低有关，而且与血睾屏障完整性受损有关。此外，对于女性而言，PFOA 和 PFOS 与性激素水平异常有关，并增加了不孕和月经周期异常的风险。尽管如此，关于 PFOA 和 PFOS 与精子质量和生殖激素之间的流行病学关系仍存在争议证据，而来自动物研究的证据则相对一致。根据已发表的论文，本文综述了 PFOA、PFOS 及其替代品的潜在毒性机制。对于男性，PFOA 和 PFOS 可能通过以下五种方式产生生殖毒性：（1）生精细胞凋亡和自噬；（2）睾丸间质细胞凋亡和分化障碍；（3）精子氧化应激和质膜钙通道紊乱；（4）Sertoli 细胞之间精细细胞间连接的降解；（5）脑核激活和下丘脑代谢组移位。对于女性，PFOA 和 PFOS 可能通过以下五种方式产生生殖毒性：（1）通过氧化应激损伤卵母细胞；（2）抑制黄体功能；（3）抑制类固醇激素合成；（4）通过影响缝隙连接细胞间通讯（GJIC）损伤卵泡；（5）抑制胎盘功能。此外，PFAS 替代品具有与 PFOA 和 PFOS 相似的生殖毒性，对胎盘的毒性更大。最后，基于现有知识，提出了该领域未来的发展方向和努力方向。
