Transgenerational Effects of Exposure of 2 2' 3 3'4 4' 5 5' 6 6'-decabromodiphenyl Ether (BDE-209) during Prenatal Period on Testicular and Sperm Functions and DNA methylation in Rats

• Main Authors: LI, ZHENG-KUAN, 李政寬
• Other Authors: HSU, PING-CHI
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/mwf49f

碩士 === 國立高雄科技大學 === 環境與安全衛生工程系 === 107 === Background: Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that have been widely used in many products to reduce fire risk by mixing polymer products. There are still few studies to investigate the transgenerational and epigenetic effects of decabromodiphenyl ether (BDE-209) on male reproductive function. The purpose of this study was to evaluate the transgenerational effects of pregnant rats (F0) prenatal exposure to BDE-209 on male reproductive dysfunctions and associated sperm DNA methylation epimutations in rat male offspring. Methods: Pregnant SD rats were treated by gavage on gestation day (GD) 0 to GD 20 with 5 mg BDE-209/kg/day based on the lowest-observed-adverse-effect level for sperm toxicity in male rats for BDE-209. F1 , F2, and F3 male offspring were killed and the epididymal sperm counts, motility, morphology, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), sperm chromatin DNA structure integrity, epigenetic sperm DNA methylation, testicular DNA content in spermatogenesis, and serum testosterone levels were assessed on postnatal day (PND) 84. An outcross experiment was performed to determine whether the transgenerational phenotype is tranfmitted through the male germ line. F1 BDE-209-treated males were bred to unexposed females to generate the F2 treated generation and F2 BDE-209-treated males were bred to unexposed females to generate the F3 treated generation. Results: We found that body weight, sperm motility, and sperm counts in BDE-209 exposed group were significantly decreased than the control group (p<0.05). There was a significant decrease in the sperm motility and normal morphology rate in the F2 generation males prenatally exposed to BDE-209 (p<0.05). Reduced serum III testosterone levels and normal morphology rate were observed in males of the F3 generation exposed group. After analyzed 3371 hyper methylation genes of biological process, there were 11 sperm DNA methylation genes with properties of androgen, 9 methylation genes of apoptosis, and 59 methylation genes of endocrine. Furthermore, we performed a Fold Change filtering between exposed and control group with methylated DNA score to focus the most significant 22 hyper-methylation and 18 hypo-methylation genes. Conclusion: The effects of F0 exposed to BDE-209 might result in male reproductive dysfunctions and associate sperm DNA methylation in F3. BDE-209-induced change in sperm DNA hyper or hypo-DNA methylation in F3 might explain the possible mechanism of BDE-209-mediated epigenetic transgenerational effects on male reproductive system.