The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal stero
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RESEARCH ARTICLE
The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal steroidogenesis disorders induced by di-(2-ethylhexyl) phthalate Tian-Xin Zhao 1,2,3,4,5,6 & Yue-Xin Wei 1,2,3,4,5 & Jun-Ke Wang 2,3,4,5,6 & Lin-Dong Han 1,3,4,5,6 & Mang Sun 2,3,4,5,6 & Yu-Hao Wu 2,3,4,5,6 & Lian-Ju Shen 2,3,4,5,6 & Chun-Lan Long 2,3,4,5,6 & Sheng-De Wu 1,2,3,4,5,6 & Guang-Hui Wei 1,2,3,4,5,6 Received: 13 February 2020 / Accepted: 22 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP. Keywords Di-(2-ethylhexyl) phthalate . Prepuberal testis . Gut microbiota . Oxidative stress . Nrf2 signaling pathway . Gut-microbiota-testis axis
Introduction Di-(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates, which are used as plasticizers to make plastics
flexible in polymer products (Praveena et al. 2018). DEHP has been widely used in the production of a multitude of plasticderived products, such as medical devices, plastic-based toys, infant products, cosmetics, and personal care products
Responsible Editor: Mohamed M. Abdel-Daim Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-020-09854-2) contains supplementary material, which is available to authorized users. * Sheng-De Wu [email protected] * Guang-Hui Wei [email protected] 1
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Department of Urology, Children’s Hospital of Chongqing Medical University, Yuzhong District, Chongqing 400014, People’s Republic of China Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, People’s Republic of China
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Ministry of Education Key Laboratory of Child Developme
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