Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters

Abstract

Women with polycystic ovarian syndrome (PCOS) undergoing treatment for infertility could be a sensitive subpopulation for endocrine effects of exposure to perfluorinated alkyl acids (PFAAs), persistent organic pollutants with potential endocrine activity. Women with, PCOS (n = 30) and age- and BMI-matched controls (n = 29) were recruited from a UK fertility clinic in 2015. Paired serum and follicular fluid samples were collected and analysed for 13 PFAAs. Sex steroid and thyroid hormones, and metabolic markers were measured and assessed for associations with serum PFAAs. Four PFAAs were detected in all serum and follicular fluid samples and concentrations in the two matrices were highly correlated (R > 0.95): perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Serum PFOS was positively associated with age (1 ng/mL per yr, p < 0.05) and was higher in PCOS cases than controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05) and in women with irregular vs. regular menstrual cycles (GM 3.9 vs. 3.0 ng/mL, p = 0.01). After adjustment for confounders, serum testosterone was significantly associated with PFOA, PFHxS, PFNA, and the molar sum of the four frequently detected serum PFAAs (approximately 50 percent increase per ln-unit) among controls but not PCOS cases. HbA1c in PCOS cases was inversely associated with serum PFOA, PFHxs, and sum of PFAAs (2-3 mmol/mol per ln-unit). In controls, fasting glucose was positively associated with serum PFOA and sum of PFAAs (0.25 nmol/L per ln-unit increase in PFAAs). Few other associations were observed. The analyses and findings here should be considered exploratory in light of the relatively small sample sizes and large number of statistical comparisons conducted. However, the data do not suggest increased sensitivity to potential endocrine effects of PFAAs in PCOS patients.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary

“…Heffernan et al . found a positive association between PFNA exposure and A4 in both PCOS cases and controls, and a positive association between PFHxS exposure and total T in healthy women ( Heffernan et al , 2018 ). Zhang et al .…”

“…Due to the ability of albumin to pass the blood follicle barrier ( Hess et al , 1998 ; Schweigert et al , 2006 ), it is suggested that PFAAs can easily be transported into growing follicles. PFAAs have been detected in human follicular fluid and could alter oocyte maturation and follicle development in vivo ( Petro et al , 2014 ; Heffernan et al , 2018 ).…”

“…Moreover, Heffernan et al . observed a significant and negative association between PFOS exposure and free androgen index (FAI) among healthy women without PCOS ( Heffernan et al , 2018 ).…”

“…In contrast, no associations with hormone levels have been reported for PFOA exposure ( Knox et al ., 2011 ; Barrett et al ., 2015 ; McCoy et al ., 2017 ; Heffernan et al ., 2018 ; Zhang et al ., 2018 ). PFOS and PFOA were also not related to serum T levels among women 12–80 years of age from the NHANES 2011–2012 ( Lewis et al , 2015 ).…”

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

“…Currently there are no reports concerning the experimental evaluation of the dominant perfluoroalkyl acid detected in the environment, PFOA, on oocyte toxicity in mammals. However, levels of PFC, including PFOA, have been detected in the follicular fluid of women, and it was reported that women with follicular fluid PFC contamination had significantly lower fertilization rate and number of embryos transferred compared to the PFC negative group in patients undergoing IVF‐ET cycles, thus indicating possible deleterious effects of PFOA and other PFC on mammal's oocytes . Therefore, the objective in the present study was to investigate whether PFOA was able to generate ROS in murine fetal ovaries (early oogenesis) and cause oocyte death by apoptosis and/or necrosis in fetal oocytes in culture.…”