Amniotic fluid phthalate levels and male fetal gonad function

Area of Science:

• Endocrinology
• Reproductive Toxicology
• Environmental Health

Background:

• Prenatal phthalate exposure is a potential risk to male reproductive health.
• Human in vivo data on phthalate effects, particularly on genital abnormalities, are limited.
• Di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) are common phthalates of concern.

Purpose of the Study:

• To investigate the association between prenatal exposure to DEHP and DiNP metabolites and male reproductive outcomes.
• To examine effects on cryptorchidism, hypospadias, and fetal Leydig cell function.
• To analyze steroid hormone and insulin-like factor 3 levels in relation to phthalate metabolite concentrations.

Main Methods:

• Study included 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls.
• Amniotic fluid samples from a Danish biobank (1980-1996) were analyzed for DEHP and DiNP metabolites using mass spectrometry.
• Hormone levels (testosterone, insulin-like factor 3) were measured via mass spectrometry and immunoassay.

Main Results:

• The DEHP metabolite 5cx-MEPP was associated with an 18% increase in testosterone and a 41% decrease in insulin-like factor 3.
• The DiNP metabolite 7cx-MMeHP showed increased odds for cryptorchidism (OR=1.28) and hypospadias (OR=1.69), though not statistically significant.
• No consistent associations were found between DEHP metabolites and genital abnormalities, or between DiNP metabolites and hormone levels.

Conclusions:

• DEHP metabolites may interfere with human male fetal gonadal function.
• A potential association between DiNP metabolites and hypospadias, and to a lesser extent cryptorchidism, cannot be ruled out.
• Further research is needed to confirm these findings and elucidate mechanisms of phthalate-induced reproductive disruption.