Impact of obesity on male fertility, sperm function and molecular composition

Abstract

Male obesity in reproductive-age men has nearly tripled in the past 30 y and coincides with an increase in male infertility worldwide. There is now emerging evidence that male obesity impacts negatively on male reproductive potential not only reducing sperm quality, but in particular altering the physical and molecular structure of germ cells in the testes and ultimately mature sperm. Recent data has shown that male obesity also impairs offspring metabolic and reproductive health suggesting that paternal health cues are transmitted to the next generation with the mediator mostly likely occurring via the sperm. Interestingly the molecular profile of germ cells in the testes and sperm from obese males is altered with changes to epigenetic modifiers. The increasing prevalence of male obesity calls for better public health awareness at the time of conception, with a better understanding of the molecular mechanism involved during spermatogenesis required along with the potential of interventions in reversing these deleterious effects. This review will focus on how male obesity affects fertility and sperm quality with a focus on proposed mechanisms and the potential reversibility of these adverse effects.

Figure 1. The effect of male obesity on pregnancy success in couples undergoing assisted reproductive technologies. Data taken from ref. from 305 couples undergoing assisted reproductive technologies. BMI classification ranges, Normal (18.5 – 24.9 kg/m²), Overweight (25.0 – 29.9 kg/m²) and Obese (≥ 30 kg/m²). Data was analyzed through a multivariate analysis including both paternal and maternal BMI. Different letters denote significance at p < 0.05.

Figure 2. Hypothesis for the effect of male obesity on spermatogenesis and how it impacts offspring health. Paternal obesity in rodents has been shown to negatively impact the metabolic and reproductive health of offspring. Sperm are the likely mediator for altering the developmental profile of the embryo,^, fetes^, and then resultant offspring.^,,, This change is likely to be molecular in nature and resulting from impaired spermatogenesis as a result of the obesity phenotype most likely occurring through changes to acetylation, methylation or non-coding RNA status of sperm .

Figure 3. The effect of diet induced obesity in C57BL6 mice on Acetylation and DNA damage levels in spermatids during protanimation. Data taken from. Data was analyzed through a univariate general linear model with replicate fitted as a covariate and mouse ID as a random factor. Correlation data was determined by a Pearson’s Rho. (A) The effect of diet induced obesity in mice on acetylation levels of H3K9 in elongating spermatids representative of > 120 spermatids from at least 5 mice per treatment group. (B) The effect of diet induced obesity in mice on DNA damage levels in elongating spermatids representative of > 4000 spermatids from at least 5 mice per treatment group. There was a negative correlation found between acetylation levels of H3K9 and DNA damage levels in round spermatids R² = 0.60, p = 0.023 n = 8 animals.