The Effect of Dietary Micronutrient Supplementation on the Reproductive Health of Obese Males

Abstract

According to the Australian Institute of Health and Welfare, 2 in 3 Australian men are overweight or obese. Sperm oxidative stress is a common factor in various forms of male infertility including obesity, and can lead to increased sperm intracellular reactive oxygen species (ROS) and oxidative DNA lesions (8-OHdG), impaired sperm function, reduced implantation and live birth rates and the transgenerational inheritance of disease for up to two generations. According to Cochrane Reviews, the use of dietary micronutrient and antioxidant supplementation has been shown efficient in improving live birth rates in infertile men despite recent reports suggesting the evidence is of low quality. There is limited research however, regarding the effectiveness of dietary micronutrient supplements in the growing population of obese males. Therefore, the aim of this thesis was to establish the impact of a combination of dietary micronutrient supplements on male reproductive health outcomes in obese men and diet-induced obese mice. In the mouse model, male mice were fed a control diet (CD, 6% fat) or a high fat diet (HFD, 21% fat) for 10 weeks to induce obesity and then assigned to one of three dietary micronutrient supplement (selenium, vitamin C, lycopene, vitamin E, zinc, folic acid green tea extract) treatment durations: (i) 10 weeks; (ii) 5 weeks or (iii) 10 days in conjunction with their initially allocated control or HFD. In all three treatment durations, sperm morphology, intracellular ROS, 8-OHdG lesions, sperm-oocyte binding and fertilization rates were increased with micronutrient supplements in HFD-fed males compared to the un-supplemented HFD-fed mice. HFD-induced obese males treated with micronutrient supplementation for 10 days were mated with normal weight females and implantation rates were increased in addition to increased fetal weights. Also, immunofluorescence showed that 8-OHdG lesions were reduced in developing testicular spermatogenic cells and the paternal pronucleus of the subsequent embryo in males fed a HFD supplemented with micronutrients. In the retrospective and prospective studies, fertility treatment outcomes and sperm oxidative stress were assessed in non-smoking couples attending an infertility clinic whereby the male partner was aged <45 years old, of normal weight, overweight or obese BMI, and the female partner was non-obese and aged <38 years old. Couples were stratified by the male partner’s BMI and whether they were consuming micronutrient supplements (Menevit or multivitamins) at the time of treatment. Retrospective data showed that fertilization rates and on-time embryo development were increased with micronutrient supplement intake in obese men compared to obese men not consuming dietary supplements. Also, implantation and live birth rates were improved with micronutrient supplementation in all men regardless of their BMI. The prospective data showed similar results in addition to reduced sperm intracellular ROS in obese men and reduced sperm 8-OHdG lesions in all men despite BMI with micronutrient supplement intake. Overall, these findings demonstrate that micronutrient supplementation can increase implantation and live birth rates in obese males and lessen the inheritance of oxidative lesions in the male germline highlighting the importance of paternal preconception health. These studies warrant further research into potential molecular mechanisms in sperm, the testis and epididymis.