Impact of high fat diet on the sterol regulatory element-binding protein 2 cholesterol pathway in the testicle

Abstract 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 t...

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Published in:	Molecular human reproduction Vol. 27; no. 5
Main Authors:	Funes, Abi K, Simón, Layla, Colombo, Regina, Avena, María Virginia, Monclús, María, Crescitelli, Julieta, Cabrillana, María E, Conte, María Inés, Cayado, Niubys, Boarelli, Paola, Fornés, Miguel W, Saez Lancellotti, Tania E
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 08-05-2021
Subjects:	Animals Cholesterol - metabolism Diet, High-Fat Infertility, Male - metabolism Male Rabbits Real-Time Polymerase Chain Reaction Semen Analysis Sterol Regulatory Element Binding Protein 2 - metabolism Testis - metabolism cholesterol / male infertility / SREBP / spermatozoa / testicle
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Summary:	Abstract 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1360-9947 1460-2407
DOI:	10.1093/molehr/gaab023