Liu Shaozhen, Chen Yue, Li Tongyao, Qiao Liying, Yang Qiong, Rong Weiya, Liu Qing, Wang Weiwei, Song Jing, Wang Xianzong, Liu Yu
College of Animal Science, Shanxi Agricultural University, Jinzhong 030801, China.
Int J Mol Sci. 2023 Feb 10;24(4):3571. doi: 10.3390/ijms24043571.
17α-Methyltestosterone (MT), a synthetic environmental endocrine disruptor with androgenic effects, has been shown to disrupt the reproductive system and inhibit germ cell maturation in . To further investigate the regulation of gonadal development by MT through the hypothalamic-pituitary-gonadal (HPG) axis, were exposed to 0, 25, 50, and 100 ng/L of MT for 7, 14, and 21 days. We analyzed its biological indicators, gonadotropin-releasing hormone (GnRH), gonadotropins, reproduction-related gene expression, and brain tissue transcriptome profiles. We found a significant decrease in the gonadosomatic index (GSI) in males exposed to MT for 21 days compared to the control group. GnRH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, as well as the expressions of the , , , , and genes, were significantly reduced in the brains of both male and female fish when exposed to 100 ng/L MT for 14 days compared to the controls. Therefore, we further constructed four RNA-seq libraries from 100 ng/L MT-treated groups of male and female fish, obtaining 2412 and 2509 DEGs in male and female brain tissue, respectively. Three common pathways were observed to be affected in both sexes after exposure to MT, namely, nicotinate and nicotinamide metabolism, focal adhesion, and cell adhesion molecules. Furthermore, we found that MT affected the PI3K/Akt/FoxO3a signaling pathway through the upregulation of and , and the downregulation of and . Therefore, we hypothesize that MT interferes with the levels of gonadotropin-releasing hormone (GnRH, FSH, and LH) in brains through the PI3K/Akt/FoxO3a signaling pathway, and affects the expression of key genes in the hormone production pathway (, and ) to interfere with the stability of the HPG axis, thus leading to abnormal gonadal development. This study provides a multidimensional perspective on the damaging effects of MT on fish and confirms that is a suitable model animal for aquatic toxicology.
17α-甲基睾酮（MT）是一种具有雄激素作用的合成环境内分泌干扰物，已被证明会扰乱生殖系统并抑制[具体物种]的生殖细胞成熟。为了进一步研究MT通过下丘脑-垂体-性腺（HPG）轴对性腺发育的调节作用，将[具体物种]暴露于0、25、50和100 ng/L的MT中7、14和21天。我们分析了其生物学指标、促性腺激素释放激素（GnRH）、促性腺激素、生殖相关基因表达以及脑组织转录组图谱。我们发现，与对照组相比，暴露于MT 21天的[具体物种]雄性个体的性腺体指数（GSI）显著降低。当暴露于100 ng/L MT 14天时，与对照组相比，雄性和雌性鱼类大脑中的GnRH、促卵泡激素（FSH）和促黄体生成素（LH）水平以及[相关基因名称1]、[相关基因名称2]、[相关基因名称3]、[相关基因名称4]和[相关基因名称5]基因的表达均显著降低。因此，我们进一步从100 ng/L MT处理的雄性和雌性鱼类组中构建了四个RNA测序文库，在雄性和雌性脑组织中分别获得了2412个和2509个差异表达基因（DEG）。暴露于MT后，观察到两性均有三个共同的途径受到影响，即烟酸和烟酰胺代谢、粘着斑和细胞粘附分子。此外，我们发现MT通过上调[相关基因名称6]和[相关基因名称7]以及下调[相关基因名称8]和[相关基因名称9]来影响PI3K/Akt/FoxO3a信号通路。因此，我们推测MT通过PI3K/Akt/FoxO3a信号通路干扰[具体物种]大脑中促性腺激素释放激素（GnRH、FSH和LH）的水平，并影响激素产生途径中关键基因（[相关基因名称1]、[相关基因名称2]和[相关基因名称3]）的表达，从而干扰HPG轴的稳定性，进而导致性腺发育异常。本研究为MT对鱼类的损害作用提供了多维度视角，并证实[具体物种]是水生毒理学的合适模式动物。
