Morbid obesity–related changes in the expression of lipid receptors, transporters, and HSL in human sperm
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.
Ten controls and 20 obese patients.
Anthropometric parameters. Serum and semen samples were collected.
Main outcome measure(s)
Spermatozoon concentration, immunolocalization, and protein expression in semen.
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.
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.
KeywordsLipid receptors and transporters Human spermatozoa Obesity Fertility Cholesterol
We thank the members of Department of Biochemistry-Research for their help.
B.C. participated in the sample collection and data analysis and revised the manuscript.
L.H. participated in the sample collection and conducted the experiments.
M.E.C. participated in the data analysis.
J.M.G.C. participated in sample collection.
J.I.B.C. participated in the study design and revised the manuscript critically for important intellectual content.
A.M.H. participated in the study design and coordination, data analysis, and interpretation and wrote the manuscript.
Supported by Grants PI1501686 and PI1600154 from Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness. Supported in part by Fondo Europeo de Desarrollo Regional (FEDER) from the European Union. CIBERobn is also an initiative of Instituto de Salud Carlos III. Dr. Calderón received a grant from MESCYT, Dominican Republic Ministry of Superior Education.
Compliance with ethical standards
We included 10 healthy controls and 20 male patients with moderate to severe obesity who gave written informed consent to participate in a substudy and the study was approved by the Institutional Review Board of our hospital.
Conflict of interest
The authors declare that they have no conflict of interest.
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