The effect of paternal diet‐induced obesity on sperm function and fertilization in a mouse model

Abstract

Although obvious effects of obesity on female reproduction and oocytes are emerging, the effects on male fertility and sperm quality are less clear with studies reporting conflicting results. We hypothesize that male obesity affects sperm function and physiology probably as a result of elevated oxidative stress in spermatozoa and therefore elevated levels of sperm DNA damage and loss of function. Six-week-old C57/Bl6 male mice (n = 36) were randomly allocated to two groups: group 1 (n = 18) received a control diet, whereas group 2 (n = 18) received a high-fat diet (HFD). At the completion of a 9-week period, mice were sacrificed and spermatozoa were obtained. Sperm motility, concentration, intracellular reactive oxygen species (ROS) production and sperm DNA damage were measured. The ability of the sperm to undergo capacitation, acrosome reaction, sperm binding and ability to fertilize an oocyte were also assessed. The percentage of motile spermatozoa was decreased in the HFD group compared with controls (36 ± 2% vs. 44 ± 4%; p < 0.05). Intracellular ROS was elevated (692 ± 83 vs. 409 ± 22 units; p < 0.01) in the HFD group compared with controls. Sperm DNA damage was also increased (1.64 ± 0.6% vs. 0.17 ± 0.06%; p < 0.05) in the HFD group compared with the control group. Furthermore, the percentage of non-capacitated sperm was significantly lower compared with controls (12.34% vs. 21.06%; p < 0.01). The number of sperm bound to each oocyte was significantly lower (41.14 ± 2.5 vs. 58.39 ± 2.4; p < 0.01) in the HFD group compared with that in controls and resulted in significantly lower fertilization rates (25.9% vs. 43.9%; p < 0.01). This report provides evidence that obesity may induce oxidative stress and sperm DNA damage as well as decreased fertilizing ability. This is important as DNA damage in the sperm as a result of oxidative stress has been linked to poor reproductive outcomes.

Female offspring sired by diet induced obese male mice display impaired blastocyst development with molecular alterations to their ovaries, oocytes and cumulus cells

“…The model of paternal diet induced obesity used here recapitulated that sperm from males fed a HFD had reduced motility and increased levels of intracellular ROS, compared to sperm from CD fed males. This is consistent with previous studies in similar models that demonstrate that not only does HFD feeding result in an obese phenotype [9, 11, 12, 14-16, 32, 36-38] but also correlates with impaired sperm quality [15,16,[36][37][38]. Although testosterone concentrations were not measured in these HFD fed males, we speculate that their observed subfertility may be associated with lowered testosterone concentrations, as previously demonstrated [36,37].…”

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

“…Studies on obese men (Kort et al 2006, Chavarro et al 2009 showed increased numbers of sperm with DNA fragmentation, findings that are partly corroborated by animal studies that have shown a small increase in sperm with nDNA damage (Bakos et al 2011) and evidence of one of its consequences, decreased implantations (Ghanayem et al 2010). This contrasts with the findings of our study, that showed no difference in the sperm nDNA status of either animal model.…”

Nutritional modifications in male infertility: a systematic review covering 2 decades

“…27 Some components of high-energy diets, such as trans fatty acids and saturated fats, have the potential to adversely affect the testicular lipid metabolism and impair sperm production. In another animal study, Bakos et al 40 reported that paternal-diet-induced obesity decreased both the motility and the fertilizing ability of sperm in male mice. Morgan et al 34 also reported that elevated levels of plasma cholesterol induced by a cholesterol-rich diet negatively affected spermatogenesis in rabbits.…”