Effects of dioxins on animal spermatogenesis:A state-of-the-art review

The male reproductive system is especially affected by dioxins, a group of persistent environmental pollutants, resulting in irreversible abnormalities including effects on sexual function and fertility in adult males and possibly on the development of male offspring. The reproductive toxicity caused by dioxins is mostly mediated by an aryl hydrocarbon receptor (AhR). In animals, spermatogenesis is a highly sensitive and dynamic process that includes proliferation and maturation of germ cells. Spermatogenesis is subject to multiple endogenous and exogenous regulatory factors, including a wide range of environmental toxicants such as dioxins. This review discusses the toxicological effects of dioxins on spermatogenesis and their relevance to male infertility. After a detailed categorization of the environmental contaminants affecting the spermatogenesis, the exposure pathways and bioavailability of dioxins in animals was briefly reviewed. The effects of dioxins on spermatogenesis are then outlined in detail. The endocrine-disrupting effects of dioxins in animals and humans are discussed with a particular focus on their effects on the expression of spermatogenesis-related genes. Finally, the impacts of dioxins on the ratio of X and Y chromosomes, the status of serum sex hormones, the quality and fertility of sperm, and the transgenerational effects of dioxins on male reproduction are reviewed

2,3,7,8-tetrachlorodibenzo-p-dioxin induces multigenerational testicular toxicity and biosynthetic disorder of testosterone in BALB/C mice: Transcriptional, histopathological and hormonal determinants

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent environmental contaminant, is an endocrine disrupter with a proven reproductive toxicity in mammals. However, its effects on male fertility across generations are still elusive. The current work evaluates the toxicity of dioxin on male reproductive system in two separate groups of BALB/C mice; a group of pubertal males directly exposed to TCDD (referred to as DEmG), and a group of indirectly exposed males (referred to as IDEmG) comprises of F1, F2 and F3 males born from TCDD-exposed pregnant females. Both groups were exposed to 25 μg TCDD/kg body weight for a week. Our data show that males of TCDD-DEmG exhibited significant alterations in the expression of certain genes involved in the detoxification of TCDD and the biosynthesis of testosterone. This was accompanied with testicular pathological symptoms, including a sloughing in the germinal epithelium and a congestion of blood vessels in interstitial tissue with the presence of multinuclear cells into seminiferous tubule, with a 4-fold decline in the level of serum testosterone and reduced sperm count. Otherwise, the male reproductive toxicity across F1, F2 and F3 generations from TCDD-IDEmG was mainly characterized by: i) a reduce in body and testis weight. ii) a decrease in gene expression of steriodogenesis enzyme, e.g., AhR, CYP1A1, CYP11A1, COX1, COX2, LOX5 and LOX12. iii) a remarked and similar testicular histopathology that found for DEmG, iv) a serious decline in serum testosterone. v) a decreased male-to-female ratio. vi) a low sperm count with increasing abnormalities. Thus, pubertal or maternal exposure to TCDD provokes multigenerational male reproductive toxicity in mice, ultimately affecting the spermatogenesis and suggesting that the hormonal alternation and sperm abnormality are the most marked effects of the indirect exposure of mammalian male to TCDD

Additional file 2: Table S2. of Immuno-detection of dioxins using a recombinant protein of aryl hydrocarbon receptor (AhR) fused with sfGFP

The different additives used for refolding the sfGFP-AhR. The basic information of the different additives used for solubilizing the sfGFP-AhR from the inclusion bodies. (DOC 95 kb

Additional file 4: Figure S2. of Immuno-detection of dioxins using a recombinant protein of aryl hydrocarbon receptor (AhR) fused with sfGFP

The structure of the plasmid pRSET-sfGFP-AhR. Map of the plasmid construct pRSET-sfGFP-AhR, in which the inserted AhR (LBD) is indicated. The most important elements of the plasmid are shown, including the T7 promoter, N-terminal 6×His tag, two restriction sites (BamHI/EcoRI) used for insert ligation, ampicillin resistance gene (Amp), f1/PUC origin of replication and the sfGFP gene. (DOC 266 kb

Additional file 1: Table S1. of Immuno-detection of dioxins using a recombinant protein of aryl hydrocarbon receptor (AhR) fused with sfGFP

The primers used for the amplification and cloning of the AhR. The different parameters (application, name, length and sequence) of the primers used for AhR gene amplification and cloning into the pRSET-sfGFP plasmid. (DOC 79 kb

Additional file 3: Figure S1. of Immuno-detection of dioxins using a recombinant protein of aryl hydrocarbon receptor (AhR) fused with sfGFP

Alignment of the AhR(LBD) amino acids sequences. Amino acids sequence alignment of the AhR(LBD) from human (hAhR, NP_001612), mouse (mAhR, NP_038492) and rat (rAhR, NP_037281). Similarity bar above the sequences and the different secondary structures (as attributed by Geneious software) are indicated with small arrows. The TCDD binding cavity and the PAS-B domains are indicated through which small boxes under the sequence refer to the amino acids whose side chains are implicated in the structure of the cavity (light coloured for lateral and dark for internal positions), as described before [31]. (DOC 272 kb