Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility

Abstract

Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

Obesity, a serious etiologic factor for male subfertility in modern society

“…Meanwhile, the replacement of histone by protamines in late round spermatids also plays a critical role in sperm DNA protection. Histone acetylation is necessary for histones replacement by protamines, and alterations in histone acetylation are commonly found in the diet-induced obese mouse models, resulting in increased levels of DNA damage (Gaucher et al 2010, Palmer et al 2011, Davidson et al 2015. On the other hand, because of the limitation in antioxidant defensive capacity and defectiveness in DNA repair system, the DNA damage induced by ROS in spermatozoa is particularly crippling and increases the risk of failure in further fertilization and embryonic development (Gavriliouk & Aitken 2015).…”

Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men

“…Hypo-androgenism is associated with generalised depression and lethargy, plus the more specific sexual symptoms of erectile dysfunction and diminished desire [6], all significantly reducing men’s quality of life [2]. While weight loss usually results in normalisation of androgen levels and spermatogenesis [4, 7–9], unfortunately most obese men are unable to achieve this goal and therefore continue to suffer from the adverse effects of hypogonadism.…”

Changing of the ejaculate parameters and sperm structure in men with overweight

“…Так, у пациентов с варикоцеле и инфекционными заболеваниями урогенитального тракта часто выявляют астенозооспермию (снижение подвижности сперматозоидов), возникающую в ре-зультате множественных структурных нарушений в цитоскелете жгутика. По данным некоторых авторов [1,2,10,11,18], астенозооспермия является частой патологией и у мужчин с ожирением. Возможными причинами могут быть гипертермия и оксидативный стресс, возникающие в результате увеличения про-слойки жировой ткани в мошонке.…”

“…Согласно вышесказанному, можно предполо-жить, что у мужчин с избыточной массой тела макро-скопические показатели спермограммы должны быть хуже, чем у мужчин с нормальным ИМТ [2].…”