Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic. Issue 7 (18th February 2021)

• Record Type: Journal Article
• Authors: Gong, Yingyun; Xue, Yanfeng; Li, Xin; Zhang, Zhao; Zhou, Wenjun; Marcolongo, Paola; Benedetti, Angiolo; Mao, Shengyong; Han, Leng; Ding, Guolian; Sun, Zheng
• Is Part Of: Advanced science. Volume 8:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-18
• Subjects: arsenic -- diabetes -- environmental health -- epigenetic inheritance -- metabolism -- obesity; Science -- Periodicals; 505
• DOI: 10.1002/advs.202002715
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross‐generational effects of iAs in an exclusive male‐lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6‐phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male‐lineage iAs exposure show increased adiposity, especially on a high‐calorie diet. These findings have unveiled sex‐ and generation‐specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene‐environment interactions. Abstract : Inorganic arsenic (iAs) has sex‐ and generation‐specific heritable effects on metabolic physiology in mammals through the male germline lineage. Paternal exposure to iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males. F2 offspring from grand paternal iAs exposure show reduced adiposity. F3 offspring of the male‐lineage iAs exposure show increased adiposity.