ACUTE vs. CHRONIC RESPONSE OF SREBP2 PATHWAY TO FAT DIET IN RABBIT TESTICLES

AVENA MARIA; BOARELLI P; SAEZ LANCELLOTTI , ESTEFANIA; FUNES ABI; CRESCITELI JULIETA; MONCLUS MARÍA ANGELES; COLOMBO REGINA; ROLDAN, ADRIÁN; FORNES MIGUEL

VIRTUAL

Congreso; IV Reunión Conjunta de Sociedades de Biología de la Argentina; 2020

Male fertility has been shown to be dependent on cholesterol (chol) homeostasis. Chol is essential for testosterone synthesis and spermatogenesis. For proper functioning of the testicles, chol should be maintained in an optimal ratio. We have previously shown that rabbits under a high fat diet (HFD) exhibit low seminal quality related to an overload of cholesterol in cells of the seminiferous tubule. The aim of this work was to study the molecular pathway that regulates the intracellular chol, controlled by the Sterol regulatory element-binding proteins (SREBPs), in the testicles of animals under HFD. To investigate this, we took advantage of our previously developed hypercholesterolemic model in New Zealand rabbits (HCR) that display poor seminal quality. The expression of SREBP-2 was studied under acute (HCR ≤ 6M, less than 6 months of diet) and chronic (HCR ≥ 12M, more than 12 months of diet) intake of HFD (14% bovine grease w/w) by RT-PCR, western blot and immunofluorescence. Our findings show that fat consumption promoted significant down regulation in both SREBP-2 mRNA and protein in the testicle at 6 months (42 % and 48 % respectively), but significant upregulation after a chronic period (160 % and 30 % respectively). This was consistent with an accumulation of testicular cholesterol, assessed by Filipin III staining. However, both blood lipid alterations and seminal deleterious changes were evident from the acute intake period. Furthermore, by indirect immunofluorescence, the sub-cellular location of SREBP-2 protein in the testicle was determined. In conclusion, the pathway that regulates chol levels in the testicle is sensitive to dietary fat, and behaves differently according to the time the rabbits spend consuming fat: a protective effect can be observed in the short term, but it is deregulated in the long term. This ultimately leads to a detrimental situation, related to poor seminal quality.