High-fat diet aggravates prenatal low-dose DEHP exposure induced spermatogenesis disorder: Characterization of testicular metabolic patterns in mouse offspring. (July 2022)

• Record Type: Journal Article
• Authors: Fan, Yun; Xu, Qiaoqiao; Qian, Hong; Tao, Chengzhe; Wan, Tingya; Li, Zhi; Yan, Wenkai; Niu, Rui; Huang, Yuna; Chen, Minjian; Xu, Qiujin; Martin, Elizabeth M.; Wang, Xinru; Qin, Yufeng; Lu, Chuncheng
• Is Part Of: Chemosphere. Volume 298(2022)
• Publication Date: 2022-07
• Subjects: DEHP -- HFD -- WCNA -- Male adult offspring -- Reproductive dysfunction; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.134296
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and has been identified as a male prenatal reproductive toxicant. A high fat diet (HFD) has also been suggested as another potential disruptor of male reproductive function. Despite this potential synergism between DEHP exposure and HFD, little is known about the concomitant effects of prenatal DEHP and a subsequent HFD exposure on male offspring reproductive injury. Here we established a mouse model of prenatal exposure to DEHP (0.2 mg/kg/day) to assess the testicular development and spermatogenesis in offspring subjected to obesogenic diet during the pubertal period. Gross phenotype, hormone profiles and the testicular metabolome were analyzed to determine the underlying mechanism. We found that prenatal exposure to low-dose DEHP resulted in decreased sperm density, decreased testosterone (T) levels, increased luteinizing hormone (LH) levels and testicular germ cell apoptosis. Furthermore, these injury phenotypes were aggravated by pubertal HFD treatment. Testicular riboflavin and biotin metabolites were enriched implying their roles in contributing HFD to exacerbate offspring spermatogenesis disorders due to prenatal low-dose DEHP exposure. Our findings suggest that pubertal HFD exacerbates reproductive dysfunction associated with prenatal exposure to low-dose DEHP in male adult offspring. Graphical abstract: Image 1 Highlights: Pubertal HFD exacerbates the male offspring reproductive dysfunction resulting from prenatal low-dose DEHP exposure. Pubertal HFD exacerbates sex hormone alterations and testicular apoptosis in offspring exposed to prenatal low-dose DEHP. Testicular metabolites are significantly associated with the phenotypes altered by prenatal DEHP exposure and pubertal HFD. Riboflavin and biotin contribute to HFD exacerbated spermatogenesis disorders due to prenatal low-dose DEHP exposure.