Gestational exposure to low‐dose zearalenone disrupting offspring spermatogenesis might be through epigenetic modifications

Abstract

Zearalenone (ZEA), a F‐2 mycotoxin produced by Fusarium, has been found to be an endocrine disruptor through oestrogen receptor signalling pathway to impair spermatogenesis. The disruption on reproductive systems by ZEA exposure might be transgenerational. In our previous report, we have found that low dose (lower than no‐observed effect level, NOEL) of ZEA impaired mouse spermatogenesis and decreased mouse semen quality. The purpose of the current investigation was to explore the impacts of low‐dose ZEA on spermatogenesis in the offspring after prenatal exposure and the underlying mechanisms. And it demonstrated that prenatal low‐dose ZEA exposure disrupted the meiosis process to inhibit the spermatogenesis in offspring and even to diminish the semen quality by the decrease in spermatozoa motility and concentration. The DNA methylation marker 5hmC was decreased, the histone methylation markers H3K9 and H3K27 were elevated, and oestrogen receptor alpha was reduced in the offspring testis after prenatal low‐dose ZEA exposure. The data suggest that the disruption in spermatogenesis by prenatal low‐dose ZEA exposure may be through the modifications on epigenetic pathways (DNA methylation and histone methylation) and the interactions with oestrogen receptor signalling pathway. Moreover, in the current study, the male offspring were indirectly exposed to low‐dose ZEA through placenta and the spermatogenesis in offspring was disrupted which suggested that the toxicity of ZEA on reproductive systems was very severe. Therefore, we strongly recommend that greater attention should be paid to this mycotoxin to minimize its adverse impact on human spermatogenesis.

Estrogen Receptor-Related DNA and Histone Methylation May Be Involved in the Transgenerational Disruption in Spermatogenesis by Selective Toxic Chemicals

“…Moreover, we found that 5hmC was mainly expressed in spermatogonia stem cells (SSCs; Men et al, 2019). The number of 5hmC-positive SSCs in F0 mouse testes was significantly diminished by NH 4 Cl-50mg/kg, NH 4 Cl-10mg/kg + Na 2 S-10mg/kg, and NH 4 Cl-50 mg/kg + Na 2 S-50 mg/kg exposure ( Figures 3A, B ).…”

Environmental contaminants and male infertility: Effects and mechanisms

“…was increased along with the decreased expression of testicular ERα in mice exposed to ZEA (Gao et al, 2015;Men et al, 2019). These studies revealed the crucial role of interactions between the oestrogen signalling pathway and genetic and epigenetic pathways in mediating the adverse effects of ZEA on spermatogenesis (Gao et al, 2015;Men et al, 2019).…”

“…was increased along with the decreased expression of testicular ERα in mice exposed to ZEA (Gao et al, 2015;Men et al, 2019). These studies revealed the crucial role of interactions between the oestrogen signalling pathway and genetic and epigenetic pathways in mediating the adverse effects of ZEA on spermatogenesis (Gao et al, 2015;Men et al, 2019). Kim et al reported nonylphenol in-duced pathophysiological abnormalities in testis and epididymis of F2 mice, which were suggested to be a result of epigenetic reprogramming by nonylphenol exposure (Kim et al, 2019).…”

Environmental Impact on Male (In)Fertility via Epigenetic Route

“…Concomitantly with these findings, the authors report the disruption of meiosis and decreased sperm quality [ 192 ]. Moreover, the same group—using the same doses—further explored the consequences of prenatal exposure to zearalenone in ICR mice and found that, irrespective of the strain used, a global reduction in both DNA methylation and estrogen alpha can still be observed, paralleled by elevated histone methylation of H3K9 and H3K27 [ 193 ]. Given the effects reported, further attention should be given to zearalenone and caution must be taken when dealing with products contaminated with this EDC.…”