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Impact of high fat diet on the sterol regulatory element-binding protein 2 cholesterol pathway in the testicle
Molecular Human Reproduction ( IF 4 ) Pub Date : 2021-03-30 , DOI: 10.1093/molehr/gaab023
Abi K Funes 1, 2 , Layla Simón 1 , Regina Colombo 1, 2 , María Virginia Avena 1, 2 , María Monclús 1, 3 , Julieta Crescitelli 2, 3 , María E Cabrillana 1 , María Inés Conte 1 , Niubys Cayado 3, 4 , Paola Boarelli 5 , Miguel W Fornés 1 , Tania E Saez Lancellotti 1, 2, 3
Affiliation  

Male fertility has been shown to be dependent on cholesterol homeostasis. This lipid is essential for testosterone synthesis and spermatogenesis, but its levels must be maintained in an optimal range for proper testicular function. In particular, sperm cells’ development is very sensitive to high cholesterol levels, noticeably during acrosomal formation. The aim of this work was to study whether the molecular pathway that regulates intracellular cholesterol, the sterol regulatory element-binding protein (SREBP) pathway, is affected in the testicles of animals under a fat diet. To investigate this, we took advantage of the non-obese hypercholesterolemia (HC) model in New Zealand rabbits that displays poor sperm and seminal quality. The testicular expression of SREBP isoform 2 (SREBP2) and its target molecules 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and low-density lipoprotein receptor (LDLR) were studied under acute (6 months) and chronic (more than 12 months) fat intake by RT–PCR, western blot and immunofluorescence. Our findings showed that fat consumption promoted down-regulation of the SREBP2 pathway in the testicle at 6 months, but upregulation after a chronic period. This was consistent with load of testicular cholesterol, assessed by filipin staining. In conclusion, the intracellular pathway that regulates cholesterol levels in the testicle is sensitive to dietary fats, and behaves differently depending on the duration of consumption: it has a short-term protective effect, but became deregulated in the long term, ultimately leading to a detrimental situation. These results will contribute to the understanding of the basic mechanisms of the effect of fat consumption in humans with idiopathic infertility.

中文翻译:

高脂饮食对睾丸中甾醇调节元件结合蛋白2胆固醇通路的影响

男性生育能力已被证明依赖于胆固醇稳态。这种脂质对于睾酮合成和精子发生至关重要,但其水平必须保持在最佳范围内,以确保睾丸功能正常。特别是,精子细胞的发育对高胆固醇水平非常敏感,尤其是在顶体形成期间。这项工作的目的是研究调节细胞内胆固醇的分子途径,即甾醇调节元件结合蛋白 (SREBP) 途径,是否在脂肪饮食动物的睾丸中受到影响。为了对此进行调查,我们利用了新西兰兔的非肥胖高胆固醇血症 (HC) 模型,该模型显示精子和精液质量较差。在急性(6个月)和慢性(超过 12 个月)通过 RT-PCR、蛋白质印迹和免疫荧光检测的脂肪摄入量。我们的研究结果表明,脂肪消耗促进了睾丸中 SREBP2 通路在 6 个月时的下调,但在慢性期后上调。这与通过菲律宾染色评估的睾丸胆固醇负荷一致。总之,调节睾丸中胆固醇水平的细胞内通路对膳食脂肪很敏感,并且根据食用时间的不同而表现不同:它具有短期保护作用,但在长期内变得失调,最终导致不利的局面。这些结果将有助于理解脂肪消耗对特发性不孕症患者的影响的基本机制。
更新日期:2021-03-30
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