Perfluorooctane Sulfonate Concentrations in Amniotic Fluid, Biomarkers of Fetal Leydig Cell Function, and Cryptorchidism and Hypospadias in Danish Boys (1980-1996)

Background: Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development.

Objectives: We aim to study the associations between amniotic fluid PFOS level and fetal steroid hormone and Insulin-like factor 3 (INSL3) level as well as the prevalence of cryptorchidism and hypospadias.

Methods: Utilizing the Danish National Patient Registry, we selected 270 cryptorchidism cases, 75 hypospadias cases and 300 controls with stored maternal amniotic fluid samples available in a Danish pregnancy-screening biobank (1980-1996). PFOS was measured in amniotic fluid from 645 persons and steroid hormones in samples from 545 persons by mass spectrometry. INSL3 was measured by immunoassay from 475 persons. Associations between PFOS concentration in amniotic fluid, hormone levels and genital malformations were assessed by confounder adjusted linear and logistic regression.

Results: The highest tertile of PFOS exposure (>1.4 ng/ml) in amniotic fluid was associated with a 40% (95% CI: -69,-11%) lower INSL3 level and an 18% (95% CI: 7, 29 %) higher testosterone level compared to the lowest tertile (<0.8 ng/ml). Amniotic fluid PFOS concentration was not associated with cryptorchidism or hypospadias.

Conclusions: Environmental PFOS exposure was associated with steroid hormone and INSL3 concentrations in amniotic fluid, but was not associated with cryptorchidism or hypospadias in our study population. Additional studies are needed to determine whether associations with fetal hormone levels may have long-term implications for reproductive health.