In Australia, the rate of obesity among men of reproductive age has more than tripled in the last three decades. Previously, we demonstrated that paternal obesity resulted in retarded preimplantation embryo development, disproportionate changes in blastocyst metabolism and reduced cell number when embryos were generated by mating animals. Subsequently, using in vitro fertilisation we found embryos of obese males to have altered precompaction metabolism, 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 fluid respectively. Here we hypothesise that both sperm and seminal fluid are affected by obesity, compromising embryogenesis and pregnancy health in a cumulative manner.
Seminal vesicle fluid and epididymal sperm were collected from control (normal diet/weight) and obese C57BL/6 mice. Gas chromatography-mass spectrometry was employed to analyse the metabolite composition of seminal vesicle fluid. RNA was extracted from sperm samples as well as IVF derived blastocysts and placenta (embryo transfer) generated from the same sperm, and converted to cDNA for gene expression analysis via RT-qPCR. Twenty four genes of interest were selected across the three tissue types based on literature review and previous embryo culture results.
Nuclear encoded cytochrome c oxidase subunit IV isoform 1 (COX4I1) of the terminal enzyme in the mitochondrial respiratory chain had significantly increased expression in the sperm of obese males (p<0.05). Also, PPARA expression was significantly reduced in the placenta of male but not female conceptuses generated from obese males, compared to control (p<0.05). The carbohydrate composition of seminal vesicle fluid was distinctly different between control and obese.
This study has revealed that paternal diet affects both sperm function and seminal fluid composition, and furthermore that diet can alter sperm gene expression. The interaction between sperm and seminal fluid warrants further analysis.