Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model.
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.
Department of Zoology, University of Melbourne, Parkville 3010, VIC, Australia Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg 3084, VIC, Australia nkbinder@unimelb.edu.au.
Natalie K
NK
Binder
Department of Zoology, University of Melbourne, Parkville 3010, VIC, Australia.
John R
JR
Sheedy
Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg 3084, VIC, Australia.
Natalie J
NJ
Hannan
Department of Zoology, University of Melbourne, Parkville 3010, VIC, Australia.
David K
DK
Gardner
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007248:Infertility, Male / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D012661:Semen / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000235:genetics / Q000378:metabolism*; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation
D007328:Insulin; D020738:Leptin; D021122:Protein Subunits; D012333:RNA, Messenger; D029589:Seminal Plasma Proteins; D004958:Estradiol; C000604261:Cox4i1 protein, mouse; D003576:Electron Transport Complex IV
fructose; high-fat; infertility; semen; sperm