Mechanisms of Obesity-induced Male Infertility

Karen P Phillips; Nongnuj Tanphaichitr


Expert Rev Endocrinol Metab. 2010;5(2):229-251. 

In This Article

Five-year View

The issue of infertility in the obese male is critical in the context of the obesity epidemic in the Western world. Within the next 5 years, the obesity epidemic will begin to evolve into the Type 2 diabetes epidemic, with an explosion of men and women developing insulin resistance. As we learn more about the molecular biology underlying insulin resistance, the intriguing findings of concomitant suppression of Leydig cell testosterone production may be further elucidated. Certainly, there is a need for more robust studies examining semen quality in insulin-resistant men. Adipocytokines are hormones released from adipocytes, including leptin (reviewed here), resistin and adiponectin. Investigation of the physiological roles of these adipocytokines is in its infancy, although links between adipocytokines and insulin resistance have already been postulated. Kisspeptins and their modulation of the hypothalamic–pituitary–gonadal axis in both men and women is a field that is developing at a rapid pace. Understanding the neuroendocrine modulation of the reproductive system and its potential sensitivity to endocrine disrupters and nutritional stressors will contribute significantly to this field. The contribution of environmental stressors (nutrition, endocrine disrupters and infectious agents) to fetal development, and ultimately adult-onset diseases, including obesity and infertility, will be investigated using molecular approaches. Although this review has focused on male infertility, the potential for environmental stressors to create epigenetic changes to the germ line will have important implications for future generations. Endocrine disrupters, particularly environmental estrogens, are well-established reproductive toxicants and target steroid hormone signaling pathways associated with nuclear receptor superfamily members. The recent characterization of nongenomic steroid hormone receptors has the potential to revolutionize the field of endocrinology. Chemicals with the capacity to perturb adipose physiology have only recently been identified and termed obesogens or metabolic disrupters. The importance of these chemicals to obesity, diabetes and male infertility remains to be elucidated.


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