A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development

Abstract

The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.

Risk factors for cryptorchidism

“…Similarly, studies that have measured testosterone levels in cord blood found no evidence of an association between reduced testosterone levels and the development of cryptorchidism. 55,56 …”

“…58 In recent years, it has been reported that cord blood levels of INSL3 are lower in children born with cryptorchidism 5655,59 and might be reduced by exposure to exogenous endocrine-disrupting chemicals. 56,60 However more direct observation of the pathway between exogenous stimuli (such as chemicals), altered intrauterine INSL3 levels and cryptorchidism development is required in order to substantiate causality. The role of endocrine-disrupting chemicals as a risk factor for cryptorchidism is discussed elsewhere in this review.…”

“…Some authors have observed higher levels of the compounds bisphenol A , 176 dibutylin 169 dioxin , 164,173 heptachloroepoxide , 174 hexachlorobenzene , 174 polychlorinated biphenyls 164,173,177 and polybrominateddiphenyl ethers 159,164 among boys (and/or their mothers) who developed cryptorchidism compared to those who did not; however a substantial number of studies (at least some of which were adequately powered to detect an association) have directly evaluated these and other biologically-plausible compounds and found no such association. 56,60,152–157,160,163,168,172,178 In some cases, studies have found substantial regional heterogeneity, including conflicting results between countries within the same study. 161,162,164,169 For example, Rantakokko et al 169 observed that maternal exposure to high levels (>0.15ng/g) of dibutylin was associated with increased risk of cryptorchidism in Danish sons (adjusted OR vs. <0.10ng/g: 4.01, 95% CI 1.42–11.33), but was inversely associated in Finnish sons (adjusted OR: 0.16, 95% CI 0.03–0.75).…”

Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process

“…Although development of steroidogenic capacity in testis was affected by exposure to BPA and DEHP, expression of the Insl3 protein, a marker for Leydig cell differentiation, was unchanged as measured in 35 day-old male rats. However, BPA treatment increased Insl3 mRNA expression in the human but not rodent fetal testis (43) while BPA concentrations were negatively correlated with cord blood Insl3 concentrations in boys (44). The fetal testis was not analyzed for Insl3 expression in the present study, but there is evidence showing that EDCs may regulate factors other than Insl3 that affect development of steroid hormone secretion capacity.…”

Human exposure to endocrine disrupting chemicals as a prenatal risk factor for cryptorchidism

“…Pesticides have also been detected in amniotic fl uid, umbilical cord blood, meconium, and infant urine, indicating the exposure of the fetus to pesticides (37,38). In one of the most recent studies conducted in France, bisphenol A measured in cord blood correlated negatively with INSL3 but not with testosterone (39). The diff erences in dimethyl (DM) metabolites in pregnant women across the world may be due to diff erences in pesticide use among diff erent countries and diff erences in diet among populations.…”