zearalenone and Infertility--Male

Zearalenone (ZEA) is a nonsteroidal estrogen-like mycotoxin widely distributed in maize, wheat, rice and other cereals with its derivants. It also presents in meat or dairy products or even in the aquatic ecosystem via rain, and thus can affect human health. ZEA affects the body function in various ways. On the one hand, it can disturb the synthesis of estrogen and its combination with the receptor, influence the reproductive ability via the estrogen signaling pathway, and cause the dysfunction of the reproductive systems. On the other hand, it can disturb the synthesis of DNA and proteins and result in lipid peroxidation and cytotoxicity by inducing the apoptosis of germ cells. It is known that exposure to different doses of ZEA can affect the female reproductive system by increasing the apoptosis of germ cells and inducing germ cell prematurity, sexual precocity, endocrine disorder, reproductive cycle disorder, and so on. But studies of its influence on the male reproductive system are relatively rare, especially about its unique male-related action mechanisms. This review presents an overview of the studies on the mechanisms of ZEA affecting male fertility and the phenotype changes in the male reproductive system after exposure to ZEA, hoping to provide some new ideas for the protection of human fertility.. 玉米赤霉烯酮（ZEA）是一种具有类雌激素作用的非甾体类霉菌毒素，ZEA及其衍生物广泛分布于水稻、玉米和小麦等农作物中，还可以富集于牲畜的肉制品、奶制品中，并可以通过雨水等途径进入水生系统，具有影响人类健康的充分条件。ZEA可以通过多种途径影响机体的功能，一方面，它能够扰乱雌激素的合成代谢及与受体的结合，通过干扰雌激素信号通路来影响动物的生殖能力，造成生殖机能紊乱；另一方面，它还能够干扰DNA和蛋白质合成，引起脂质过氧化作用等，通过诱导凋亡等途径对细胞产生毒性作用，导致生殖细胞的异常死亡。目前已知各种剂量的ZEA暴露可以对雌性生物的生殖系统产生诸如增加生殖细胞凋亡、导致生殖细胞早衰、性早熟、内分泌紊乱、生殖周期紊乱等影响。但对雄性生殖系统的影响研究相对较少，尤其缺少对雄性生物生殖毒性作用途径不同的、雄性性别相关的特有机制的研究。本文将介绍已知的ZEA对雄性生物生殖毒性的作用机制，并总结ZEA暴露使雄性生物生殖系统发生的表象变化，旨在为人类男性生殖能力下降的研究提供新的理论依据和研究方向，进而为人类生殖能力的保全和提升提供新的思路。.

Topics: Apoptosis; Estrogens, Non-Steroidal; Fertility; Humans; Infertility, Male; Male; Signal Transduction; Zearalenone

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.

Topics: Animals; Animals, Newborn; Disease Models, Animal; DNA Methylation; Dose-Response Relationship, Drug; Endocrine Disruptors; Epigenesis, Genetic; Female; Histone Code; Humans; Infertility, Male; Male; Maternal Exposure; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; No-Observed-Adverse-Effect Level; Pregnancy; Prenatal Exposure Delayed Effects; Semen Analysis; Signal Transduction; Sperm Motility; Spermatogenesis; Testis; Zearalenone