School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia.
Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW, Australia.
Reprod Fertil. 2024 Mar 8;5(1). doi: 10.1530/RAF-23-0087. Print 2024 Jan 1.
Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization.
PFAS are synthetic chemicals widely used in non-stick cookware, food packaging, and firefighting foam. Such extensive use has led to concerning levels of environmental contamination and reports of associations with a spectrum of negative health outcomes, including testicular cancer and reduced semen quality. To investigate the effects of PFAS on male reproduction, we incubated mouse sperm in a cocktail of nine PFAS at environmentally relevant concentrations before checking for a range of functional outcomes. This treatment strategy was not toxic to the sperm; it did not kill them or reduce their motility, nor did it affect their fertilization capacity. However, we did observe developmental delays among pre-implantation embryos created using PFAS-treated sperm. Such findings raise the intriguing prospect that PFAS-exposed sperm harbor a form of stress signal that they deliver to the embryo upon fertilization.
多氟和全氟烷基物质（PFAS）是合成的具有环境持久性的化学物质。尽管已经淘汰了某些 PFAS，但它们固有的稳定性导致了无处不在且持久的环境污染。PFAS 已在全球范围内被发现存在于大多数人群中，它们与一系列负面健康影响有关，包括与睾丸癌发病率增加和整体精液质量下降的强烈关联。为了阐明这些影响的生物学基础，我们采用了一种急性体外暴露模型，在该模型中，成年雄性小鼠的精子在环境相关浓度下暴露于 PFAS 化学物质混合物中。我们假设，PFAS 直接处理精子会诱导活性氧的产生，并损害暴露细胞的功能特征和 DNA 完整性。尽管如此，暴露后的功能测试表明，短期 PFAS 暴露（3 小时）不会引起细胞毒性，也不会明显影响精子的功能特征、获能率或体外受精能力。然而，PFAS 处理精子确实导致体外产生的第 4 天胚胎的发育进程显著延迟。这种发育延迟不能归因于精子 DNA 完整性的丧失、DNA 损伤或细胞内活性氧水平的升高。综合考虑，这里呈现的结果提出了一个有趣的观点，即暴露于短期 PFAS 暴露期的精子可能携带潜在的替代应激信号，该信号在受精时传递给胚胎。
PFAS 是一种广泛用于不粘炊具、食品包装和消防泡沫的合成化学品。这种广泛的用途导致了令人担忧的环境污染水平，并报告了与一系列负面健康结果的关联，包括睾丸癌和精液质量下降。为了研究 PFAS 对男性生殖的影响，我们将老鼠精子在环境相关浓度的九种 PFAS 混合物中孵育，然后检查一系列功能结果。这种处理策略对精子没有毒性；它没有杀死它们，也没有降低它们的活力，也没有影响它们的受精能力。然而，我们确实观察到使用 PFAS 处理的精子产生的着床前胚胎发育延迟。这些发现提出了一个有趣的观点，即暴露于 PFAS 的精子携带一种应激信号，在受精时传递给胚胎。
