Molecular Shadows of Per- and Polyfluoroalkyl Substances (PFASs): Unveiling the Impact of Perfluoroalkyl Substances on Ovarian Function, Polycystic Ovarian Syndrome (PCOS), and In Vitro Fertilization (IVF) Outcomes
Charalampos Voros, Diamantis Athanasiou, Ioannis Papapanagiotou, Despoina Mavrogianni, Antonia Varthaliti, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, George K. Papadimas, Athanasios Gkirgkinoudis, Kyriaki Migklis, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Charalampos Τsimpoukelis, Sofia Ivanidou, Anahit J. Stepanyan, Maria Anastasia Daskalaki, Marianna Theodora, Panagiotis Antsaklis, D. Loutradis, G. Daskalakis
Abstract
Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic-pituitary-ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women's reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments.