Department of Anesthesiology, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China; Department of Pathology, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Department of Pain management, Wuhan Fourth Hospital, No. 473, Hanzheng Street, Qiaokou District, Wuhan, Hubei 430033, China.
Ecotoxicol Environ Saf. 2023 Mar 1;252:114568. doi: 10.1016/j.ecoenv.2023.114568. Epub 2023 Jan 23.
Citrinin, a mycotoxin existing in fruits, has nephrotoxicity, hepatotoxicity and embryotoxicity. The effects of citrinin on Leydig cell development in prepuberty remains unclear. Male Sprague-Dawley rats were gavaged with 0, 1, 2.5, and 5 mg/kg citrinin from postnatal days 21-28. Citrinin at 5 mg/kg significantly decreased serum testosterone levels, while increasing serum LH and FSH levels. Citrinin at 1-5 mg/kg markedly downregulated Hsd17b3 and HSD17B3 expression, while upregulating Srd5a1 (SRD5A1) and Akr1c14 (AKR1C14) expression at 2.5 and/or 5 mg/kg. Citrinin at 5 mg/kg also significantly increased PCNA-labeling index in Leydig cells. Citrinin at 5 mg/kg significantly raised testicular MDA amount, whiling at 2.5 and 5 mg/kg downregulating SOD1 and SOD2 expression. Citrinin at 5 mg/kg markedly decreased the ratio of Bcl2 to Bax, in consistent with the increased apoptosis in Leydig cells judged by TUNEL assay. Enzymatic assay revealed that citrinin inhibited rat testicular HSD3B1 activity at 100 µM and HSD17B3 activity at 10-100 μM. Citrinin at 50 μM and higher also induced reactive oxygen species (ROS) and apoptosis of R2C cell line. In conclusion, citrinin inhibits Leydig cell development at multiple levels via different mechanisms and oxidative stress partially plays a role.
桔青霉素是一种存在于水果中的真菌毒素，具有肾毒性、肝毒性和胚胎毒性。桔青霉素对青春期前莱迪希细胞发育的影响尚不清楚。雄性 Sprague-Dawley 大鼠从出生后第 21-28 天开始每天灌胃 0、1、2.5 和 5mg/kg 桔青霉素。5mg/kg 的桔青霉素显著降低了血清睾酮水平，同时增加了血清 LH 和 FSH 水平。1-5mg/kg 的桔青霉素显著下调了 Hsd17b3 和 HSD17B3 的表达，而在 2.5 和/或 5mg/kg 时上调了 Srd5a1（SRD5A1）和 Akr1c14（AKR1C14）的表达。5mg/kg 的桔青霉素也显著增加了 Leydig 细胞的 PCNA 标记指数。5mg/kg 的桔青霉素显著增加了睾丸 MDA 含量，而在 2.5 和 5mg/kg 时下调了 SOD1 和 SOD2 的表达。5mg/kg 的桔青霉素显著降低了 Bcl2 与 Bax 的比值，与 TUNEL 检测到的 Leydig 细胞凋亡增加一致。酶活性测定表明，桔青霉素在 100μM 时抑制大鼠睾丸 HSD3B1 活性，在 10-100μM 时抑制 HSD17B3 活性。50μM 及更高浓度的桔青霉素也诱导了 R2C 细胞系的活性氧（ROS）和凋亡。综上所述，桔青霉素通过不同的机制在多个水平上抑制莱迪希细胞的发育，氧化应激在其中部分发挥作用。
