Dietary Micronutrient Supplementation for 12 Days in Obese Male Mice Restores Sperm Oxidative Stress.

Nicole O Mcpherson,Deirdre L Zander-Fox,Michelle Lane,Tod Fullston,Helana Shehadeh

doi:10.3390/nu11092196

Abstract

Male obesity, which often co-presents with micronutrient deficiencies, is associated with sub-fertility. Here we investigate whether short-term dietary supplementation of micronutrients (zinc, selenium, lycopene, vitamins E and C, folic acid, and green tea extract) to obese mice for 12 days (designed to span the epididymal transit) could improve sperm quality and fetal outcomes. Five-week-old C57BL6 males were fed a control diet (CD, n = 24) or high fat diet (HFD, n = 24) for 10 weeks before allocation to the 12-day intervention of maintaining their original diets (CD, n = 12, HFD n = 12) or with micronutrient supplementation (CD + S, n = 12, HFD + S, n = 12). Measures of sperm quality (motility, morphology, capacitation, binding), sperm oxidative stress (DCFDA, MSR, and 8OHdG), early embryo development (2-cell cleavage, 8OHdG), and fetal outcomes were assessed. HFD + S males had reduced sperm intracellular reactive oxygen species (ROS) concentrations and 8OHdG lesions, which resulted in reduced 8OHdG lesions in the male pronucleus, increased 2-cell cleavage rates, and partial restoration of fetal weight similar to controls. Sub-fertility associated with male obesity may be restored with very short-term micronutrient supplementation that targets the timing of the transit of sperm through the epididymis, which is the developmental window where sperm are the most susceptible to oxidative damage.

Highlights

The prevalence of obesity has more than doubled in the last three decades making obesity in adults more common than under-nutrition [1]
We have previously shown that lifestyle interventions including changing to a low saturated fat nutrient matched diet coupled with light exercise for 2.5 months in our rodent model of obesity reduces adiposity, reduces sperm reactive oxygen species (ROS), and associated oxidative DNA damage, and reverses the adverse fetal outcomes associated with male obesity [11,26,27,28]
Males fed a high fat diet (HFD) were heavier from 7 weeks on the diet, which resulted in a 24% increase in total weight gained during the pre-intervention period compared with males fed a control diet (CD) (Figure 1A,B, p < 0.05)

Summary

Introduction

The prevalence of obesity has more than doubled in the last three decades making obesity in adults more common than under-nutrition [1] This is most evident in westernized societies including. A recent systematic review found that men who are obese have decreased total sperm counts, lower sperm mitochondrial membrane potential, and increased sperm DNA damage, resulting in a higher odds ratio of experiencing infertility in the general population [5]. These sperm traits were coupled with reduced live birth rates after. There is a need for clinically applicable interventions in obese men prior to conception to help improve both sperm quality but to break the transgenerational disease cycle

Methods

Results

Discussion

Conclusion