Berniza Calderón1,2, Lydia Huerta3, María Emilia Casado3,4, José Manuel González-Casbas5, José Ignacio Botella-Carretero2,4, Antonia Martín-Hidalgo6,7,8. 1. Instituto Tecnológico Santo Domingo (INTEC), Santo Domingo, República Dominicana. 2. Departamento de Endocrinología y Metabolismo, Madrid, Spain. 3. Servicio de Bioquímica-Investigación, Madrid, Spain. 4. CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII, Madrid, Spain. 5. Instituto Europeo de Fertilidad y Unidad de Reproducción Asistida, Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS), Hospital Universitario Ramón y Cajal, E-28034, Madrid, Spain. 6. Servicio de Bioquímica-Investigación, Madrid, Spain. antonia.martin@hrc.es. 7. CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII, Madrid, Spain. antonia.martin@hrc.es. 8. Department of Biochemistry-Research, Hospital Universitario Ramón y Cajal, Ctra.ColmenarViejo, Km 9.100, E-28034, Madrid, Spain. antonia.martin@hrc.es.
Abstract
OBJECTIVE: To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. DESIGN: Observational study. SETTING: None PATIENT(S): Ten controls and 20 obese patients. INTERVENTION(S): Anthropometric parameters. Serum and semen samples were collected. MAIN OUTCOME MEASURE(S): Spermatozoon concentration, immunolocalization, and protein expression in semen. RESULTS: Spermatozoon concentration and motility was decreased in morbidly obese patients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obese patients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obese patients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obese patients. CONCLUSION(S): The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obese patients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility.
OBJECTIVE: To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. DESIGN: Observational study. SETTING: None PATIENT(S): Ten controls and 20 obesepatients. INTERVENTION(S): Anthropometric parameters. Serum and semen samples were collected. MAIN OUTCOME MEASURE(S): Spermatozoon concentration, immunolocalization, and protein expression in semen. RESULTS: Spermatozoon concentration and motility was decreased in morbidly obesepatients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obesepatients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obesepatients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obesepatients. CONCLUSION(S): The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obesepatients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility.
Entities:
Keywords:
Cholesterol; Fertility; Human spermatozoa; Lipid receptors and transporters; Obesity
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