Effects of intrauterine exposure to 2,3′,4,4′,5‐pentachlorobiphenyl on the reproductive system and sperm epigenetic imprinting of male offspring

Abstract

Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3′,4,4′,5‐pentachlorobiphenyl (PCB118) is one of the most important dioxin‐like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant mice were exposed to 0, 20 and 100 μg/kg/day of PCB118 during the stage of fetal primordial germ cell migration. Compared with the control group, we found morphological alterations of the seminiferous tubules and a higher sperm deformity rate in the male offspring in the treatment groups. Furthermore, the methylation patterns in the treatment groups of the imprinted genes H19 and Gtl2 in the sperm were altered in the male offspring. We also characterized the disturbance of the expression levels of DNA methyltransferase 1 (Dnmt1), Dnmt3a, Dnmt3b, Dnmt3l, and Uhrf1. The results indicated that intrauterine exposure to low doses of PCB118 could significantly damage the reproductive health of the male offspring. Therefore, attention should be paid to the adverse effects of PCB118 exposure during pregnancy on the reproductive system of male offspring.

Exposure to human relevant mixtures of halogenated persistent organic pollutants (POPs) alters neurodevelopmental processes in human neural stem cells undergoing differentiation

“…Halogenated persistent organic pollutants (POPs) are long-lived compounds that are present in our daily environment and of concern to human health [ 1 ]. The toxic properties of POPs are well documented and many are classified as carcinogenic (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) [ 2 ], polybrominated diphenyl ethers (PBDEs) [ 3 ], immunotoxic (e.g., perfluoroalkyl substances (PFASs) [ 4 ], or neurotoxic (e.g., BDE-47 [ 5 ], and may affect reproduction and development (e.g., PCB-118 [ 6 ], endosulfan [ 7 ]). Brominated and chlorinated POPs are hydrophobic [ 8 ] and accumulate mainly in lipid rich tissues, while perfluorinated compounds tend to show a higher affinity for plasma proteins [ 9 ].…”

Systematic review of associations of polychlorinated biphenyl (PCB) exposure with declining semen quality in support of the derivation of reference doses for mixture risk assessments

“…The studies were conducted in rats, mice or goats. We identified four studies examining the effects of PCB-77 [ 39 – 42 ], two studies on those of PCB-118 [ 43 , 44 ], four studies which looked at PCB-126 [ 39 , 45 – 47 ], two studies for PCB-132 [ 48 , 49 ], one study for PCB-149 [ 48 ], two studies reporting on PCB-153 [ 45 , 50 ], two on PCB-169 [ 51 , 52 ] and one report on PCB-180 [ 53 ]. All these studies were selected for the data extraction process.…”

“…Of the two studies of PCB-118, one was conducted in the rat [ 43 ], and the other in mice [ 44 ]. We rated the key elements of the study by Kuriyama and Chahood as “probably low risk” or “definitely low risk”, but failed some of the additional elements and therefore assigned an overall Medium confidence ( TIER 2 ) [ 43 ].…”

“…We rated the key elements of the study by Kuriyama and Chahood as “probably low risk” or “definitely low risk”, but failed some of the additional elements and therefore assigned an overall Medium confidence ( TIER 2 ) [ 43 ]. The mouse study was “definitely low” or “probably low risk” in all elements and was therefore considered TIER 1 or of High confidence [ 44 ]. Both studies reported a decline in semen quality.…”

Prenatal Environmental Exposure to Persistent Organic Pollutants and Reproductive Hormone Profile and Pubertal Development in Dutch Adolescents

“…There are not many studies reporting on underlying mechanisms for an up-regulation of reproductive hormone levels and larger testicular volumes after higher prenatal PCB exposure. One possible underlying mechanism could be a decrease in expression of DNA methyltransferases, as has been found in mice exposed to PCBs [ 36 ]. With regard to a study in mice, He et al reported that intra-uterine exposure to PCB-118 was associated with an increased testicular coefficient (expressed as percentage of organ weight in live body weight) in male offspring compared to unexposed mice.…”