Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Environ Pollut. 2020 Aug;263(Pt B):114357. doi: 10.1016/j.envpol.2020.114357. Epub 2020 Mar 13.
Zearalenone is a phenolic Fusarium mycotoxin, which is ubiquitous in human and animal feedstuff and often co-occurs with other mycotoxins. ZEA has been reported to disturb Leydig cell function and even cause the apoptosis to the Leydig cells. However, the effects of gestational exposure to zearalenone on fetal Leydig cells and the underlying mechanism remain unknown. Sprague Dawley dams were daily gavaged with 0, 2.5, 5, 10, and 20 mg/kg body weight ZEA from gestational day 14-21. On gestational day 21, rats were euthanized and serum testosterone levels were measured, and testes were collected for further evaluation of Leydig cell number, cell size, gene, and protein expression. Zearalenone significantly decreased anogenital distance and its index of male fetus, serum testosterone levels, Leydig cell proteins (SCARB1, STAR, CYP11A1, CYP17A1, and INSL3), and fetal Leydig cell number at 10 and/or 20 mg/kg by delaying the commitment of stem Leydig cells into the Leydig cell lineage and proliferation. Further study found that Notch signaling (RFNG, PSEN1, NOTCH1, and NOTCH3) was up-regulated by zearalenone. In conclusion, gestational exposure to high doses of zearalenone (10 and 20 mg/kg) blocks fetal Leydig cell development, thus possibly causing the anomalies of the male reproductive tract.
玉米赤霉烯酮是一种酚类镰刀菌真菌毒素，普遍存在于人类和动物饲料中，常与其他真菌毒素共存。已有报道称玉米赤霉烯酮会干扰间质细胞功能，甚至导致间质细胞凋亡。然而，妊娠期暴露于玉米赤霉烯酮对胎儿间质细胞的影响及其潜在机制尚不清楚。SD 孕鼠从妊娠第 14 天至 21 天每天经口灌胃 0、2.5、5、10 和 20mg/kg 体重的玉米赤霉烯酮。在妊娠第 21 天，处死大鼠并测量血清睾酮水平，收集睾丸进一步评估间质细胞数量、细胞大小、基因和蛋白表达。玉米赤霉烯酮通过延迟干细胞向间质细胞谱系的分化和增殖，显著降低了雄性胎儿的肛殖距及其指数、血清睾酮水平、间质细胞蛋白（SCARB1、STAR、CYP11A1、CYP17A1 和 INSL3）和胎儿间质细胞数量，在 10 和/或 20mg/kg 时达到了统计学意义。进一步的研究发现，玉米赤霉烯酮上调了 Notch 信号通路（RFNG、PSEN1、NOTCH1 和 NOTCH3）。综上所述，妊娠期暴露于高剂量的玉米赤霉烯酮（10 和 20mg/kg）会阻断胎儿间质细胞的发育，从而可能导致男性生殖道畸形。
