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Testosterone disruptor effect and gut microbiome perturbation in mice: Early life exposure to doxycycline

文献类型： 外文期刊

作者： Hou, Xiang 1 ; Zhu, Lei 1 ; Zhang, Xianwei 3 ; Zhang, Lili 1 ; Bao, Hongduo 1 ; Tang, Minmin 2 ; Wei, Ruicheng 1 ; Wang, 1 ;

作者机构： 1.Jiangsu Acad Agr Sci, Inst Food Safety & Nutr, Nanjing, Jiangsu, Peoples R China

2.Minist Agr, Key Lab Food Qual & Safety Jiangsu Prov, Risk Assessment Lab Agroprod Proc Qual & Safety N, State Key Lab Breeding Base, Nanjing, Jiangsu, Peoples R China

3.Nanjing Med Univ, Childrens Hosp, Nanjing, Jiangsu, Peoples R China

关键词： Antibiotic; Endocrine disrupting chemicals; Mitochondrial dysfunction; Leydig cells; Testosterone

期刊名称：CHEMOSPHERE （ 2020影响因子：7.086； 五年影响因子：6.956 ）

ISSN： 0045-6535

年卷期： 2019 年 222 卷

页码：

收录情况： SCI

摘要： Veterinary tetracyclines drugs are emerging organic pollutants detected at high concentrations in the urine of school children and a potential public health risk. However, the implications of early-life exposure to tetracyclines on testosterone production, being new endocrine disruptors, remain unknown. We investigated whether the early-life exposure to low-doxycycline, a widely used tetracycline, on mitochondria dysfunction and testosterone disruption in Leydig cells in vitro and in vivo. Next, we determined the mRNA levels of testis cells markers for early-life exposure to low-doxycycline outcomes of testis health in later-life. Finally, we compared the weight gain performance exposed to low- and therapeutic-doses through 15 weeks and examined the role of the microbiota during development. Our results showed doxycycline disturbed steroidogenesis process by mitochondrial dysfunction in mouse Leydig tumor cell line (MLTC-1) cells in vitro. Leydig cells mitochondrial function was disrupted by early-life exposure to low-doxycycline from birth to 49 days, causing testosterone deficiency and decreased quality of the sperm in mice. Early-life exposure to low-doxycycline significantly altered the mRNA levels of key genes in Leydig cells (Cyp11a1, Cyp17a1 and 17 beta-HSD) and spermatogenic cells (Grfal, Plzf, and Stra8) in later-life in mice. Subchronic low- and therapeutic-doses doxycycline changed gut microbiota differences in diversity reduction and compositional alteration. Moreover, the weight gain effects of doxycycline were only observed in low-dose in male mice. Overall, these results provide insight into the effects of doxycycline on both testis and gut microbiota health. The results provide insight that envi- ronmental antibiotics are needed additional research to classify as ECDs. (C) 2019 Published by Elsevier Ltd.

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