Higher clusterin immunolabeling and sperm DNA damage levels in hypertensive men compared with controls

• Published in: Human reproduction (Oxford) 2012-08, Vol.27 (8), p.2267-2276
• Main Authors: Muciaccia, Barbara, Pensini, Simona, Culasso, Franco, Padula, Fabrizio, Paoli, Donatella, Gandini, Loredana, Di Veroli, Claudio, Bianchini, Gabriella, Stefanini, Mario, D'Agostino, Angela
• Format: Article
• Language: English
• Subjects: Adult; Age; Biological and medical sciences; Case-Control Studies; Clusterin; Clusterin - chemistry; Cohort Studies; Data processing; Diabetes mellitus; DNA Damage; DNA Fragmentation; Drugs; Fertility; Flow cytometry; Flow Cytometry - methods; Glycoproteins; Glycoproteins - chemistry; Gynecology. Andrology. Obstetrics; Humans; Hypertension; Hypertension - metabolism; Hypertension - pathology; Immunofluorescence; In Situ Nick-End Labeling; Male; Medical sciences; Metabolic disorders; Microscopy, Fluorescence - methods; Middle Aged; Mortality; Motility; Obesity; Regression Analysis; Reproductive system; Semen; Semen - metabolism; Side effects; Sperm; Spermatozoa - metabolism; Spermatozoa - pathology
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/des173

BACKGROUND Clusterin, a heterodimeric glycoprotein found at several sites in the human male reproductive tract, could be a marker of morphologically abnormal spermatozoa, while TUNEL positivity indicates DNA fragmentation. Metabolic disorders such as diabetes mellitus and obesity may compromise sperm quality and fertility of men; however, little evidence specifically links hypertension with the impairment of male reproductive function. METHODS By flow cytometric, immunofluorescence (TUNEL assay and clusterin immunolabeling) and immunohistochemical (peroxidase-streptavidin method) analyses, we have compared both clusterin- and TUNEL labeling in ejaculated spermatozoa from healthy normotensive donors and hypertensive subjects with the purpose to reveal possible differences between the two conditions. RESULTS Data analysis from the normotensive (n = 25) and hypertensive subjects (n = 25) demonstrate a significant correlation between high levels of clusterin immunolabeling and the presence of sperm DNA damage, which is often associated with abnormal morphology. In the normotensive subjects, a low percentage (15.3 ± 4.5) of spermatozoa positive for high levels of clusterin was detected; however, this percentage significantly increased (30.9 ± 13.0) (P < 0.01) in hypertensive subjects. Standard semen evaluations does not reveal any significant differences between the two groups of subjects, except for a reduced forward motility and lower sperm vitality in the hypertensive subjects. CONCLUSIONS This pilot study strongly suggests a relationship between hypertension and markers indicative of poor sperm quality. In hypertensive subjects, high levels of clusterin immunolabeling identified a consistent fraction of ejaculated spermatozoa carrying both DNA fragmentation and strong morphological alterations, which was not correlated with age or with sperm cell mortality. The alternative possibility that sperm damage observed is due to adverse effects of anti-hypertensive drugs does not find support in the literature nor in the drug data sheets. The relationship observed between hypertension and human semen represents a novel and possibly relevant information to be considered in the study of male fertility.