Background
It is known that the endocrine (hormone) system is vulnerable to environmental influences. Endocrine disrupting chemicals (EDCs) can alter function(s) of the endocrine system and cause adverse health effects to exposed individuals – and potentially their children and subsequent generations.
EDCs are now essentially ubiquitous in our environment, and there is growing concern about the detrimental health effects of these chemicals, for which there is little or no safety data.
Important health lessons have been learned from past toxic level exposures to substances such as lead, polychlorinated biphenyls and diethylstilbestrol.
However, it is increasingly apparent that low level chronic exposure to EDCs may be very harmful to endocrine health, including fertility.
Perfluoroalkyl substances (commonly known as PFCs) are found in many household items, have been implicated in disrupting endocrine function, accumulate in the environment and can remain in the body for a long time.
Aim
To investigate the relationship between PFC exposure and male reproductive health.
Methods
A cross-sectional study was conducted between June 2017 and May 2018 within an annual screening protocol study designed to evaluate male reproductive health in high schools in Padova, Italy.
Participants were divided by geographical areas known to have different PFC exposure levels into high- and medium- exposed (n = 212) and non-exposed (n = 171; control) groups, and this was confirmed by quantifying PFC concentrations.
Outcome measures included anthropometric measurements, testicular ultrasound, semen analysis, and sex hormones. In an effort to elucidate mechanistic information, the authors also performed biochemical studies in established in vitro experimental models.
Results
A total of 212 men (mean age 18.7 years) in the exposed group and 171 men (mean age 18.5 years) in the control group were included in the study.
The exposed group had significantly decreased anthropometric measurements, including testicular volume (14.7 vs 16.1 mL), penile length (8.6 vs 9.7 cm) and anogenital distance (a marker of fetal testosterone exposure; 4.1 vs 4.5cm).
There was also a reduction in sperm quality in the exposed group, in particular these men had fewer sperm with a normal morphology (6.1 vs 7.9%). Samples from a subset of 100 participants (50 from each group) underwent further analyses.
Higher concentrations of PFCs in plasma and seminal fluid in the exposed group were confirmed and were significantly correlated with an increase in serum testosterone (19.3 vs 15.4 nmol/L), accompanied by a rise in LH (5.5 vs 4.2 U/L).
At in vitro concentrations similar to those measured in the exposed group, subtypes of PFCs elicited a negative effect on testosterone action at the androgen receptor (AR).
Further experiments were conducted on perfluorooctanoic acid (PFOA), the subtype of PFCs present in highest concentration. These demonstrated that PFOA reduced binding of testosterone to AR by ~35% and, in a dose-dependent manner, decreased AR nuclear translocation.
Conclusions
Young men with high levels of exposure to a class of EDCs known as PFCs had higher levels of testosterone and a reduction in semen quality, testicular volume, penile length and ano-genital distance. PFCs likely mediate this effect via an antagonistic effect on testosterone binding to the androgen receptor.
