Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, 510632, China.
Environ Toxicol. 2018 Mar;33(3):351-360. doi: 10.1002/tox.22522. Epub 2017 Dec 7.
Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male offspring arises much concern recently, but its toxic effects on the development of Leydig cells and androgen synthesis have not been elucidated. In this study, female rats were exposed to Cd during gestation and lactation, and the development of Leydig cells in the first filial-generation (F1) male rats was investigated. The steroidogenic signaling pathway and biomarkers related to the development of Leydig cells were detected to disclose how maternal Cd-exposure caused reproductive damage. F1 male rats with maternal Cd-exposure gained a low relative weight of testis and declined levels of steroid hormones. Maternal Cd-exposure interrupted the development of Leydig cells with high expression of SRD5α and cell morphology of immature Leydig cells in adulthood, inhibited the activation of cyclic adenosine monophosphate/ protein kinase A signaling pathway and down-regulated the steroidogenic enzymes. These results would help to disclose the origin of male sexual dysfunction in the developmental stages of Leydig cells.
母体暴露于镉(Cd)对雄性后代睾丸间质细胞的毒性作用最近引起了广泛关注,但 Cd 对睾丸间质细胞发育和雄激素合成的毒性作用尚未阐明。在这项研究中,雌性大鼠在妊娠期和哺乳期暴露于 Cd,研究了第一代(F1)雄性大鼠睾丸间质细胞的发育情况。检测了与睾丸间质细胞发育相关的甾体生成信号通路和生物标志物,以揭示母体 Cd 暴露如何导致生殖损伤。母体 Cd 暴露的 F1 雄性大鼠睾丸相对重量降低,甾体激素水平下降。母体 Cd 暴露中断了睾丸间质细胞的发育,成年后 SRD5α 表达升高,细胞形态呈未成熟睾丸间质细胞样,抑制环腺苷酸/蛋白激酶 A 信号通路的激活,并下调甾体生成酶。这些结果有助于揭示睾丸间质细胞发育阶段男性性功能障碍的起源。