Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model
Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model
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DOI：
10.1093/molehr/gav010
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发表时间：
2015-05-01
影响因子：
4
通讯作者：
Gardner, David K.
中科院分区：
文献类型：
--
作者：
Binder, Natalie K.;Sheedy, John R.;Gardner, David K.
在过去的三十年里，育龄男性的肥胖率增加了两倍。以前，我们证明了父亲肥胖导致植入前发育动力学受损，压实后代谢受损，体内产生胚胎时囊胚细胞数量减少。随后，使用体外受精，我们发现肥胖男性的胚胎在致密化前代谢发生改变，内细胞团细胞数量减少，胎儿发育迟缓这两项研究的区别分别在于胚胎产生的方法和精浆的存在与否。在这里，我们假设精子和精浆都受到肥胖的影响，以累积的方式损害胚胎发育和妊娠健康。从正常和肥胖C57 BL/6小鼠收集附睾精子和精囊液。从精子中提取RNA和DNA，分别用于qPCR和整体甲基化分析。采用蛋白质组学（Luminex）和代谢组学（GC-MS）技术分析精囊液的组成。肥胖男性精子中线粒体呼吸链末端酶细胞色素c氧化酶亚单位IV亚型1（Cox 4 i1）的RNA水平显著升高（P < 0.05）。精浆胰岛素、瘦素和雌二醇水平在正常男性和肥胖男性之间有显著性差异（P < 0.05）。此外，肥胖显著影响精囊液的代谢物组成。因此，这项研究已经确定，肥胖影响精子和精浆成分。精子和精浆之间的相互作用需要进一步分析。
The rate of obesity among men of reproductive age has tripled in the last three decades. Previously, we demonstrated that paternal obesity resulted in impaired preimplantation developmental kinetics, compromised post-compaction metabolism and decreased blastocyst cell number when embryos were generated in vivo. Subsequently, using in vitro fertilization we found embryos of obese males to have altered metabolism before compaction, reduced inner cell mass cell number and retarded fetal development-the difference between these two studies being the method of embryo generation and the presence or absence of seminal plasma, respectively. Here, we hypothesize that both sperm and seminal plasma are affected by obesity, compromising embryogenesis and pregnancy health in a cumulative manner. Epididymal sperm and seminal vesicle fluid were collected from normal and obese C57BL/6 mice. RNA and DNA were extracted from spermatozoa for qPCR and global methylation analysis, respectively. Proteomic (Luminex) and metabolomic (GC-MS) techniques were employed to analyse the composition of seminal vesicle fluid. Nuclear encoded cytochrome c oxidase subunit IV isoform 1 (Cox4i1) of the terminal enzyme in the mitochondrial respiratory chain demonstrated significantly increased RNA levels in the sperm of obese males (P < 0.05). Quantitative seminal plasma analysis identified significant changes in levels of the hormones insulin, leptin and estradiol between normal and obese males (P < 0.05). Further, the metabolite composition of seminal vesicle fluid was significantly affected by obesity. Consequently, this study has determined that obesity affects both sperm and seminal plasma composition. The interaction between sperm and seminal plasma warrants further analysis.