Submitted on April 10, 2006
Revised on July 7, 2006
Accepted on July 21, 2006
Predominance of one of the SR-BI isoforms is associated with increased esterified cholesterol levels not apoptosis in mink testis
Casimir D. Akpovi, Suk Ran Yoon, María Leiza Vitale, and R.-Marc Pelletier
Pathology and Cell Biology, Faculty of medicine, University of Montreal, Montreal, Quebec H3T 1J4
Corresponding Author: marc.pelletier{at}umontreal.ca
SR-BI contributes to the HDL-mediated cellular cholesterol efflux and is a phagocytosis-inducing phospholipid phosphatidylserine receptor in rat Sertoli cells while the spliced variant of the SR-B gene SR-BII, is implicated in the efflux of free cholesterol (FC) in macrophages. The study aimed to assess whether spontaneous autoimmune orchitis (AIO) which causes impaired clearance of apoptotic germ cells and spermatogenic arrest involves SR-BI, SR-BII, and/or cholesterol. The levels measured during development and the twelve month of the annual reproductive cycle in normal mink were compared to those in mink with spontaneous AIO. Time periods with lowest tubular esterified cholesterol (EC) levels showed maximal SR-BI and SR-BII levels and the periods when one or the other SR-BI isoform predominated showed increased EC levels and spermatogenic arrest in normal mink seminiferous tubules. In tubules with AIO, the predominance of only one or the other SR-BI isoform was the reverse of that measured in normal tubules and it was associated with an increase in EC levels not with apoptosis levels. SR-BI and SR-BII levels were not correlated with serum testosterone levels. SR-BI mainly localized to the Leydig cell, germ cell and Sertoli cell surface where its distribution was stage-specific. SR-BII was principally intracellular. Tubules from testes with AIO showed a deregulation of cholesterol homeostasis and SR-BI expression but relatively unchanged apoptosis levels. The results suggest that expression of both SR-BI isoform is required for maintenance of low EC levels and that the predominance of only one isoform is associated with accumulation of EC not apoptosis in the tubules.