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肥胖相关的脂质受体、转运体和 HSL 在人精子中的表达变化。

Morbid obesity-related changes in the expression of lipid receptors, transporters, and HSL in human sperm.

机构信息

Instituto Tecnológico Santo Domingo (INTEC), Santo Domingo, República Dominicana.

Departamento de Endocrinología y Metabolismo, Madrid, Spain.

出版信息

J Assist Reprod Genet. 2019 Apr;36(4):777-786. doi: 10.1007/s10815-019-01406-z. Epub 2019 Jan 18.

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.

摘要

目的

研究与胆固醇摄取和外排相关的受体(SR-BI/CLA-1、SR-BII 和 LDLr)和转运蛋白(ABCA1)在人精子中的位置和表达,并评估肥胖是否改变其位置/表达,以及这是否与不育有关。

设计

观察性研究。

地点

患者

10 名对照者和 20 名肥胖患者。

干预措施

人体测量参数。收集血清和精液样本。

主要观察指标

精子浓度、精液中的免疫定位和蛋白表达。

结果

肥胖患者的精子浓度和活力降低。SR-BI/CLA-1、SR-BII、LDLr 和 ABCA1 位于精子细胞膜上,肥胖患者和对照组之间的定位没有变化。对照组精子显示出高 SR-BI 表达,而其余分析的受体表达较少,表明 SR-BI/CLA-1 与人类精子胆固醇摄取/外排有关。相反,肥胖患者的精子显示出比对照组更少的 SR-BI/CLA-1 表达,而对 SR-BII、LDLr 和 ABCA1 的阳性染色更强。最后,人类精子表达 130-和 82-kDa 激素敏感脂肪酶(HSL)同工型。130-kDa 同工型在对照组精子中表达,而在肥胖患者中表达消失。

结论

脂质受体/转运蛋白和 HSL 存在于人精子中,表明它们在成熟/获能过程中起作用。肥胖患者中脂质受体/转运蛋白表达的变化以及缺乏 130-kDa HSL 同工型阻止了这些受体内化的胆固醇酯的水解,并有利于其在精子细胞质中的积累,这可能导致脂毒性和不育。

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