Laboratory of Differentiation and Radiobiology of the Gonads, CEADSV/iRCM/SCSR, Fontenay aux Roses, France.
Environ Health Perspect. 2010 Mar;118(3):331-7. doi: 10.1289/ehp.0900975. Epub 2009 Oct 14.
Cadmium (Cd) is a common environmental pollutant and a major constituent of tobacco smoke. Adverse effects of this heavy metal on reproductive function have been identified in adults; however, no studies have examined its effects on human reproductive organs during development.
Using our previously developed organ culture system, we investigated the effects of cadmium chloride on human gonads at the beginning of fetal life, a critical stage in the development of reproductive function.
Human fetal gonads were recovered during the first trimester (711 weeks postconception) and cultured with or without Cd. We used different concentrations of Cd and compared results with those obtained with mouse fetal gonads at similar stages.
Cd, at concentrations as low as 1 microM, significantly decreased the germ cell density in human fetal ovaries. This correlated with an increase in germ cell apoptosis, but there was no effect on proliferation. Similarly, in the human fetal testis, Cd (1 microM) reduced germ cell number without affecting testosterone secretion. In mouse fetal gonads, Cd increased only female germ cell apoptosis.
This is the first experimental demonstration that Cd, at low concentrations, alters the survival of male and female germ cells in humans. Considering data demonstrating extensive human exposure, we believe that current environmental levels of Cd could be deleterious to early gametogenesis.
镉 (Cd) 是一种常见的环境污染物,也是烟草烟雾的主要成分。这种重金属对生殖功能的不良影响已在成年人中得到证实;然而,尚无研究探讨其在人类生殖器官发育过程中的影响。
利用我们先前开发的器官培养系统,研究氯化镉对人类胎儿生命早期生殖器官的影响,这是生殖功能发育的关键阶段。
在妊娠第 1 期(受孕后 711 周)获取人类胎儿性腺,并在有或没有 Cd 的情况下进行培养。我们使用了不同浓度的 Cd,并将结果与类似阶段的小鼠胎儿性腺进行了比较。
低至 1μM 的 Cd 浓度显著降低了人类胎儿卵巢中的生殖细胞密度。这与生殖细胞凋亡增加相关,但对增殖没有影响。同样,在人类胎儿睾丸中,Cd(1μM)减少了生殖细胞数量,而不影响睾酮分泌。在小鼠胎儿性腺中,Cd 仅增加了雌性生殖细胞凋亡。
这是首次实验证明,低浓度的 Cd 可改变人类雄性和雌性生殖细胞的存活。考虑到广泛的人类暴露数据,我们认为当前环境水平的 Cd 可能对早期配子发生有害。