Ma Tan, Xia Yunhui, Wang Bo, Yang Fenglian, Ding Jie, Wu Jiang, Han Xiaodong, Wang Junli, Li Dongmei
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China; Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu, China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, 225001, Jiangsu, China.
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
Toxicol Lett. 2023 Mar 15;377:16-28. doi: 10.1016/j.toxlet.2023.01.009. Epub 2023 Feb 2.
Since Sertoli cells (SCs) play an essential role in providing energy for spermatogenesis, the present study aimed to investigate the effects of maternal exposure to plasticizer Dibutyl phthalate (DBP) on the onset of spermatogenesis in male offspring through the metabolism pathway as well as the underlying molecular mechanism. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. The in vivo results showed that 50 mg/kg/day DBP exposure could promote the expression of glucose metabolism-related proteins (GLUT3, LDHA, and MCT4) in the testis of 22 days male offspring. The in vitro results demonstrated that 0.1 mM monobutyl phthalate (MBP, the active metabolite of DBP) promoted the lactate production, glucose consumption, and glycolytic flux of immature SCs, which was paralleled by the upregulated expression of glucose metabolism-related proteins (GLUT1, GLUT3, LDHA, and MCT4). On the other hand, DBP/MBP increased fatty acid (FA) uptake, FA β-oxidation, and ATP production by promoting the expression of CD36 in immature SCs, which might accelerate the maturity of SCs to support the onset of spermatogenesis. Therefore, our findings provided a new perspective on glycolipid metabolism to explain prenatal DBP exposure leading to earlier onset of spermatogenesis in male offspring mice.
由于支持细胞（SCs）在为精子发生提供能量方面起着至关重要的作用，本研究旨在通过代谢途径以及潜在的分子机制，探讨母体暴露于增塑剂邻苯二甲酸二丁酯（DBP）对雄性后代精子发生起始的影响。在此，从妊娠第12.5天至分娩，对怀孕小鼠每天经口灌胃给予1 mL/kg玉米油，其中分别含0（对照）、50、250或500 mg/kg/天的DBP。体内结果表明，暴露于50 mg/kg/天的DBP可促进22日龄雄性后代睾丸中葡萄糖代谢相关蛋白（GLUT3、LDHA和MCT4）的表达。体外结果显示，0.1 mM邻苯二甲酸单丁酯（MBP，DBP的活性代谢产物）促进了未成熟支持细胞的乳酸生成、葡萄糖消耗和糖酵解通量，同时葡萄糖代谢相关蛋白（GLUT1、GLUT3、LDHA和MCT4）的表达上调。另一方面,DBP/MBP通过促进未成熟支持细胞中CD36的表达增加了脂肪酸（FA）摄取、FAβ氧化和ATP生成，这可能加速支持细胞的成熟以支持精子发生的起始。因此，我们的研究结果为糖脂代谢提供了一个新的视角，以解释产前DBP暴露导致雄性后代小鼠精子发生提前起始的现象。
