The prevalence of metabolic syndrome (MetS) has increased in alarming proportions, affecting around 20–25% of the global population.1 MetS has been defined as an increase in at least three of the following factors: abdominal obesity, blood pressure, triglycerides, cholesterol, and fasting glucose.2 Although MetS had been originally associated with advanced age, changes in lifestyle have accelerated the appearance of the symptoms, coinciding with reproductive age and becoming a risk factor for fertility disorders. Therefore, the study of the effect of MetS on fertility emerges as a novel area of research. However, a direct correlation of MetS with male infertility still remains unclear. In the case of the mouse model, most of the studies published so far have been performed in the C57BL/6 strain.3 Considering both that C57BL/6 mice are poor reproducers and that the multifactorial syndrome could be attributable to susceptibility genes modulated by the genetic background, the authors wondered whether the acquisition of a metabolic disorder could affect the fertility of males from a different mouse strain without pre-existing reproductive deficiencies. In view of this, the present study evaluates whether MetS has a negative impact on fertility and sperm function of hybrid male mice with high reproductive performance.
To induce a MetS-like condition, C57BL/6xBALB/c F1 (B6CF1) male mice were fed a high-fat diet (HFD, 30% fat) for 19 weeks, while controls received a normal-fat diet (NFD, 6% fat). HFD-fed mice ingested a higher amount of fat (p<0.01) but less total food (p<0.01) and only 12% more calories than NFD-fed animals (p<0.05), indicating that HFD-fed animals received a poor-quality diet. Since Week 11 of treatment, HFD-fed mice gained more weight compared to NFD-fed mice (p<0.001). At the end of the treatment, serum triglyceride levels were similar in both groups, but there was a significant increase in cholesterol (p<0.001), fasting glucose levels (p<0.05), and glucose intolerance (p<0.05) in HFD-fed mice, compatible with MetS acquisition. When fertility was evaluated, there was no significant difference between groups in the in vivo fertilisation rate or in the percentage of embryos that developed in vitro to blastocysts. While testicular weight and morphology were similar in both groups, HFD-fed mice presented lighter epididymides and higher amounts of gonadal fat compared to controls (p<0.01). In vitro studies were performed as a more restricted condition to unveil sperm defects. Whereas there was no difference in sperm viability, motility, or acrosome reaction between groups, sperm count was lower in HFD-diet mice compared to control (p<0.05). Finally, in vitro fertilisation assays showed no differences in either fertilisation or embryo development rates between groups.
In summary, HFD-fed B6CF1 animals developed a physiological condition compatible with MetS. However, this metabolic condition did not impact on the reproductive performance of hybrid B6CF1 animals, albeit a significant decrease in sperm count. These findings support the possibility that fertility impairment in humans could be the result of a combination of different environmental and genetic factors that may act in a cumulative manner with other predisposing factors from any of the two members of the couple.