Perfluoroalkyl and polyfluoroalkyl substance exposure and association with sex hormone concentrations: results from the NHANES 2015–2016

Xie, Xin; Weng, Xueqiong; Liu, Shan; Chen, Jingmin; Guo, Xin; Gao, Xinyu; Fei, Qiaoyuan; Hao, Guang; Jing, Chunxia; Feng, Liping

doi:10.1186/s12302-021-00508-9

Cited by 34 publications

(12 citation statements)

References 53 publications

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“…Undoubtedly future work is needed to clarify sexually dimorphic effects. 65 In summary, the present study shows that 24-h PFOA exposure in vitro inhibits androgen production but not metabolism in ILCs at physiologically relevant concentrations. 28,[36][37][38]57,58,66,67 Inhibition of androgen biosynthesis is driven by downregulations of LHCGR, CYP11A1, 3β-HSD1, and NR5A1 at both mRNA and protein levels, which correspond with decreased enzymatic activities of CYP11A1 and 3β-HSD1.…”

Section: Discussionmentioning

confidence: 50%

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Perfluorooctanoic acid inhibits androgen biosynthesis in rat immature Leydig cells

Zhang,

Hu,

2023

Environmental Toxicology

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Perfluorooctanoic acid (PFOA) is a commonly used short‐chain synthetic perfluoroalkyl agent. Immature Leydig cells (ILCs) are localized in the testis and responsible for androgen biosynthesis and metabolism. Although PFOA shows toxicity in the reproductive system, it is not clear if it disrupts the function of ILCs. In the present study, primary ILCs were isolated from 35‐day‐old rats and exposed to a range of PFOA concentrations (0, 0.01, 0.1, or 1 μM). It was determined that 0.1 or 1 μM PFOA reduced total androgen biosynthesis in ILCs. Specifically, 22R‐hydroxycholesterol (22R), and pregnenolone (P5) mediated androgen biosynthesis were reduced by 0.1 μM PFOA. PFOA also selectively downregulated mRNA and protein expressions of steroidogenic enzymes including LHCGR, CYP11A1, 3β‐HSD1, and NR5A1 at 0.01, 0.1, or 1 μM. Further analysis revealed that 0.1 μM PFOA inhibited CYP11A1 and 3β‐HSD1 enzyme activities. However, PFOA did not significantly affect androgen metabolism and turnover under any of the conditions tested. And PFOA gavaging to 35‐day‐old rats at 5 or 10 mg/kg for 7 or 14 days also reduced serum androgen levels secreted by ILCs. Moreover, PFOA gavaging also downregulated the mRNA and protein expression levels of LHCGR, CYP11A1, 3β‐HSD1, and NR5A1 in vivo. Taken together, these findings suggest that PFOA inhibits androgen biosynthesis in ILCs by selectively targeting key enzymes in the synthesis pathway.

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Section: Discussionmentioning

confidence: 50%

“…It is also notable that PFOA exposure appears to disrupt sex hormones in females in an age‐specific manner. Undoubtedly future work is needed to clarify sexually dimorphic effects 65 …”

Section: Discussionmentioning

confidence: 99%

Perfluorooctanoic acid inhibits androgen biosynthesis in rat immature Leydig cells

Zhang,

Hu,

2023

Environmental Toxicology

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“…This finding is inconsistent with a 2012-2013 study of cord blood PFAS levels from Shanghai which identified no differences in PFAS concentrations by sex. 34 Other literature, however, suggests that there are sex differences in specific analytes, including PFHxS, at older ages 43–45 and outcome-impacting sex-specific associations between PFAS and DNA methylation 33 , an epigenetic regulator of gene expression. No significant sex differences were observed in PFAS concentrations of DBS collected 4 months post-birth, however.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Per- and Polyfluoroalkyl Substance (PFAS) concentrations in a community-based sample of infants from Samoa

Heinsberg,

Niu,

Arslanian

et al. 2023

Preprint

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Per- and polyfluoroalkyl substances (PFAS) are persistent contaminants with documented harmful health effects. Despite increasing research, little attention has been given to studying PFAS contamination in low- and middle-income countries, including Samoa, where there is more recent modernization and potential window to examine earlier stages of PFAS exposure and consequences. Using data and biosamples collected through theFoafoaga o le Ola(“Beginning of Life”) Study, which recruited a sample of mothers and infants from Samoa, we conducted an exploratory study to describe concentrations of 40 PFAS analytes in infant cord blood collected at birth (n=66) and dried blood spots (DBS) collected at 4 months post-birth (n=50). Of the 40 PFAS analytes tested, 19 were detected in cord blood, with 11 detected in >10% of samples (PFBA, PFPeA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFHxS, PFOS, and 9Cl-PF3ONS); 12 analytes were detected in DBS, with 3 detected in >10% of samples (PFBA, PFHxS, and PFOS). PFAS concentrations were generally lower than those reported in existing literature, with the exception of PFHxS, which was detected at higher concentrations. In cord blood, we noted associations between higher PFHxS and male sex, higher PFPeA and residence in Northwest ‘Upolu (NWU) compared to the Apia Urban Area (AUA), and lower PFUnA and 9Cl-PF3ONS with greater socioeconomic resources. In DBS, we found associations between higher PFBA and greater socioeconomic resources, and between lower PFBA and PFHxS and residence in NWU versus AUA. However, the latter association did not hold when controlling for socioeconomic resources. Finally, we observed associations between nutrition source at 4 months and DBS PFBA and PFHxS, with formula- or mixed-fed infants having higher concentrations compared to exclusively breastfed infants. This study presents the first evidence of PFAS contamination in Samoa. Additional work in larger samples is needed to identify potentially modifiable determinants of PFAS concentrations, information that is critical for informing environmental and health policy measures.

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“…Although it is challenging to present plausible explanations with limited evidence, several potential mechanisms were proposed to explain the NMDR effects of PFAS, including estrogen-like effects, low-dose stimulation effects, and cytotoxicity. PFAS may promote modifications of endogenous hormone regulation in humans and in wildlife [19,[53][54][55]. PFAS showed weak estrogenic effects in animal experiments, which manifested in increased estrogen and progesterone concentrations or mimicked the effect of endogenous estrogen [56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Association between Perfluoroalkyl and Polyfluoroalkyl Substances and Women’s Infertility, NHANES 2013–2016

Tan

Zeng

Liang

et al. 2022

IJERPH

Self Cite

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Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used in consumer products. However, the role of PFAS in infertility is still poorly understood. A total of 788 women from the 2013–2016 nationally representative NHANES were included to explore the association between PFAS exposure and self-reported infertility. Six PFAS, including PFDE, PFNA, PFHxS, n-PFOA, n-PFOS, and Sm-PFOS, were detected by online SPE-HPLC-TIS-MS/MS. We used the generalized linear regression model (GLM), generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) to assess the single effects, non-linear relationships, and mixed effects on women’s infertility, respectively. The prevalence of self-reported infertility was 15.54% in this study. In GLM, n-PFOA showed a negative association with self-reported infertility in women for the Q3 (OR: 0.396, 95% CI: 0.119, 0.788) and Q4 (OR: 0.380, 95% CI: 0.172–0.842) compared with Q1 (p for trend = 0.013). A negative trend was also observed in n-PFOS and ∑PFOS (p for trend < 0.05). In GAM, a non-linear relationship was revealed in Sm-PFOS, which exhibits a U-shaped relationship. The BKMR model indicated that there might be a joint effect between PFAS and women’s infertility, to which PFNA contributed the highest effect (PIP = 0.435). Moreover, age stratification analysis showed a different dose–response curve in under and above 35 years old. Women under the age of 35 have a more noticeable U-shaped relationship with infertility. Therefore, the relatively low level of mixed PFAS exposure was negatively associated with self-reported infertility in women in general, and the impact of PFAS on infertility may vary among women of different age groups. Further studies are needed to determine the etiological relationship.

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Perfluoroalkyl and polyfluoroalkyl substance exposure and association with sex hormone concentrations: results from the NHANES 2015–2016

Cited by 34 publications

References 53 publications

Perfluorooctanoic acid inhibits androgen biosynthesis in rat immature Leydig cells

Perfluorooctanoic acid inhibits androgen biosynthesis in rat immature Leydig cells

Characterization of Per- and Polyfluoroalkyl Substance (PFAS) concentrations in a community-based sample of infants from Samoa

Association between Perfluoroalkyl and Polyfluoroalkyl Substances and Women’s Infertility, NHANES 2013–2016

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