Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta

Abstract

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case–control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case–control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish–Finnish joint prospective cohort study on cryptorchidism (1997–2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.

Risk factors for cryptorchidism

“…The medium for this analysis varies: many studies have used maternal blood taken during pregnancy, 152–158 although neonatal serum, 159,160 amniotic fluid, 60 breast milk, 159,161–166 placental tissue/cord blood 159–162,166–172 and adipose tissue biopsy from the child 173,174 have also been employed. Those studies investigating early-life environmental exposure to endocrine-disrupting chemicals as a risk factor for cryptorchidism have generally drawn blood from the children themselves.…”

“…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).…”

“…Maternal or childhood direct exposure to endocrine-disrupting chemicals 56,60,152–157,159,160,163,164,168,169,172–174,176–178 …”

Exposure Variation and Endocrine Disruption of the Male Reproductive System

“…Additionally, eight of the most prevalent organochlorine pesticides were significantly higher in breast milk among cryptorchid cases than controls [16]. Furthermore, breast milk PBDE and the placental dioxin-like PCB concentrations correlated positively with serum LH levels at 3 months [17,26], suggesting a mild testicular Leydig cell dysfunction linked to the exposure. …”

“…Thus, the milk sample covered a 2-month period, which reduced the problem of randomness of spot samples. Placentas were also collected for exposure analyses [26], and an analysis was made in adipose tissue samples that were collected during orchidopexy of cryptorchid boys or during herniotomy of the control boys [27]. …”