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This research investigates the association between perfluoroheptanoic acid (PFHpA) exposure and total testosterone levels in women and mice.

May 31, 2026Open Access

Association of Perfluoroheptanoic Acid With Total Testosterone: A Retrospective Study in Women of Childbearing Age and an Experimental Study in Female Mice Exposed to Perfluoroheptanoic Acid

Key Points

This research investigates the association between perfluoroheptanoic acid (PFHpA) exposure and total testosterone levels in women and mice.
Clinical data and serum samples were collected from 247 women of childbearing age.
Twenty female C57BL/6J mice were exposed to varying doses of PFHpA in a controlled experiment.
Serum hormone levels and enzyme expressions were quantified using ELISA and qPCR techniques.
PFHpA showed a positive association with total testosterone in women (β=0.51, 95% CI: 0.18, 0.30).
The high-dose PFHpA group had significantly higher testosterone levels compared to other groups (p<0.0001).
In mice, CYP11A1 levels were increased in the high-dose group compared to control and low-dose groups (p<0.01).

Abstract

Background: Multiple studies have demonstrated that exposure to perfluoroalkyl substances (PFAS) adversely affects endocrine function, reproductive health, metabolic processes, immune responses, and cardiovascular health; however, integration of population and animal studies remains limited. Methods: We collected clinical data and serum samples from 247 women of childbearing age who underwent pre-pregnancy fertility assessment at Hainan Women and Children’s Medical Center from January 2022 to June 2024. Serum samples were collected to assess the levels of PFAS. Furthermore, twenty female C57BL/6J mice, aged 8 weeks, were randomly allocated into four groups: a control group receiving an equivalent volume of a 1% Tween and 2% dimethyl sulfoxide aqueous solution, a low-dose perfluoroheptanoic acid (PFHpA) group (0.5 mg/kg/day), a medium-dose PFHpA group (5 mg/kg/day), and a high-dose PFHpA group (50 mg/kg/day). Serum reproductive hormone levels and the expression of cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), cytochrome P450 family 17 subfamily A polypeptide 1 (CYP17A1), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in the mice were quantified using enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). The associations between individual PFAS compounds and reproductive hormones, as well as intergroup mean differences, were analyzed utilizing IBM SPSS Statistics version 27. Results: In the human study, the natural logarithm of PFHpA showed a positive association with total testosterone (TT) levels, with a β of 0.51 (95% confidence interval CI for B: 0.18, 0.30). The high-dose PFHpA group exhibited elevated TT levels compared with all three other groups, with all p-values < 0.0001. Furthermore, in the animal study, CYP11A1 levels were increased in the high-dose PFHpA group compared with both the control and low-dose PFHpA groups, with all p-values < 0.01. Additionally, the high-dose PFHpA group demonstrated higher levels of CYP17A1, 3β-HSD, and 17β-HSD than all other groups, with all p-values < 0.05. Conclusions: This research concluded that PFHpA exposure affects TT levels. The increase in TT may result from upregulated expression of multiple enzymes within ovarian tissues, such as CYP11A1, CYP17A1, 3β-HSD, and 17β-HSD, following PFHpA exposure.

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