title: 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.
authors.affiliation: a Nuffield Department of Obstetrics and Gynaecology , University of Oxford , UK.
authors.forename: Lien M
authors.initials: LM
authors.lastname: Davidson
authors.affiliation: a Nuffield Department of Obstetrics and Gynaecology , University of Oxford , UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Millar
authors.affiliation: a Nuffield Department of Obstetrics and Gynaecology , University of Oxford , UK.
authors.forename: Celine
authors.initials: C
authors.lastname: Jones
authors.affiliation: a Nuffield Department of Obstetrics and Gynaecology , University of Oxford , UK.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Fatum
authors.affiliation: a Nuffield Department of Obstetrics and Gynaecology , University of Oxford , UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Coward
mesh_terms: D000273:Adipose Tissue / Q000503:physiopathology; D000328:Adult; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D015992:Body Mass Index; D004702:Endocrine Glands / Q000503:physiopathology; D044127:Epigenesis, Genetic; D004967:Estrogens / Q000032:analysis; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007248:Infertility, Male / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology*; D063766:Pediatric Obesity / Q000209:etiology; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology; D013737:Testis / Q000503:physiopathology; D013739:Testosterone / Q000032:analysis
chemical_list: D004967:Estrogens; D013739:Testosterone; D001141:Aromatase
keywords: Obesity; body mass index; hypothalamic-pituitary-gonadal axis; infertility; spermatogenesis