Metabolic syndrome-associated sperm alterations in an experimental rabbit model: Relation with metabolic profile, testis and epididymis gene expression and effect of tamoxifen treatment

The influence of metabolic syndrome (MetS) on sperm quality and function is debated. Using a well-established high fat diet (HFD) rabbit model resembling human MetS, including development of hypogonadism, we demonstrate that HFD decreased sperm motility, morphology and acrosome reaction in response to progesterone and increased sperm cholesterol content. All the above parameters were associated with most MetS features, its severity and plasma testosterone (T) at univariate analysis. After T adjustment, sperm morphology and motility retained a significant association, respectively, with mean arterial pressure and circulating cholesterol levels. MetS modified the expression of inflammatory and tissue remodelling genes in the testis and of aquaporins in the epididymis. In a multivariate analysis, sperm morphology resulted associated with testis expression of fibronectin and collagen type 1 genes, whereas motility with epididymis aquaporin 1 gene. Administration of tamoxifen, used in the treatment of idiopathic male infertility, to HFD rabbits partially restored motility, but further decreased morphology and increased spontaneous acrosome reaction, without restoring responsiveness to progesterone. Overall our results indicate that development of MetS produces detrimental effects on sperm quality and functionality by inducing metabolic disorders leading to alterations in testis and epididymis functions and evidence a role of hypertension as a new determinant of abnormal sperm morphology, in line with a previous human study from our group.