The predominance of one of the SR-BI isoforms is associated with increased esterified cholesterol levels not apoptosis in mink testis

This article is available online at http://www.jlr.org Supplementary key words hormone-sensitive lipase • cholesterol esters • steroidogenesis • spermatogenesis • fertility • sterility Spermatogenesis occurs in a series of proliferative and differentiation stages, which can be subdivided into mitotic, meiotic, and spermatogenic phases. Each phase is characterized by distinct cell types (spermatogonia, spermatocytes, and spermatids, respectively) ( 1, 2 ). Pathologic, experimental, and natural seasonal arrest of spermatogenesis are all associated with increases in lipid droplets ( 3, 4 ), indicating a close relationship between fertility and changes in lipid metabolism during spermatogenesis ( 5 ). A constant supply of cholesterol is required within Leydig cells to serve as precursor for the synthesis of steroid hormones (steroidogenesis) ( 6, 7 ), whereas in the seminiferous tubules, cholesterol is involved in germinal cell differentiation to spermatozoids (spermatogenesis or gametogenesis) ( 8 ).There is also considerable evidence indicating that cholesterol is required for the development of gametes and fertility in both sexes. Disruption of the DHCR24 gene, which encodes the cholesterol biosynthetic enzyme desmosterol reductase, causes infertility in male mice ( 9 ). In addition to cholesterol, sterol Abstract There is a tight relationship between fertility and changes in cholesterol metabolism during spermatogenesis. In the testis, class B scavenger receptors (SR-B) SR-BI, SR-BII, and LIMP II mediate the selective uptake of cholesterol esters from HDL, which are hydrolyzed to unesterifi ed cholesterol by hormone-sensitive lipase (HSL). HSL is critical

Section: Discussionsupporting

confidence: 80%

HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and disrupted lipid raft microdomains

Casado

Huerta

Ortiz

et al. 2012

“…Intercellular exchanges in the epithelium might also occur since SR-B1 was also detected on the lateral membranes (from caput segment 4 to cauda; data not shown). Such intercellular exchanges have been shown elsewhere ( 31 ).…”

Section: Ce Accumulation Enhances Apoptosis In Segment 1 Epithelial Cmentioning

confidence: 93%

LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell-specific manner

Ouvrier¹,

Cadet²,

Vernet³

et al. 2009

This article is available online at http://www.jlr.org tozoa to fully mature cells ( 1 , 2 ). Principal aspects of epididymal transformation include functional maturation, sperm concentration, storage of the spermatozoa in a quiescent state, and removal of degenerating cells. Functional maturation of these spermatozoa requires interaction of sperm with luminal fl uid, whose composition is regulated by absorption and secretion activities of the epididymal epithelium ( 3 ).The sperm plasma membrane is the site of dramatic changes throughout the development of these cells, and, in the epididymis, the remodeling process includes important modifi cations in lipid composition as well as repositioning of lipid and protein components to different membrane domains ( 4 ). The lipid composition of mammalian spermatozoa is specifi c with a large amount of plasmalogen phospholipids (PLs), a high content of long-chain PUFAs, mostly arachidonic acid (20:4, n-6), docosapentaenoic acid (22:5, n-3), and docosahexaenoic acid (22:6, n-3), and relatively low cholesterol:PL ratios ranging from 0.24 for caput epididymidis sperm to 0.29 for cauda epididymidis sperm in mice ( 5 ). This ratio is an indicator of membrane fl uidity, and although it is quite stable during epididymal transit, membrane fl uidity was shown to increase during this step ( 6 ). Earlier work showed a significant decrease of the two major PLs, phosphatidylcholine and phosphatidylethanolamine, in mouse spermatozoa from cauda epididymidis compared with those from caput epididymidis ( 5 ). During epididymal maturation, stearic acid (C18:0) decreased also, whereas palmitic acid (C16:0) increased. Among the PUFAs, docosapentaenoic and docosahexaenoic acids rose signifi cantly in the cauda epididymidis. Cholesterol content also declined by roughly 65% during epididymal maturation ( 5 ). These modifi cations have been supposed to prepare sperm cells for capacitation and acrosome reaction that take place in the Abstract Mammalian spermatozoa undergo important plasma membrane maturation steps during epididymal transit. Among these, changes in lipids and cholesterol are of particular interest as they are necessary for fertilization. However, molecular mechanisms regulating these transformations inside the epididymis are still poorly understood. Liver X receptors (LXRs), the nuclear receptors for oxysterols, are of major importance in intracellular cholesterol homeostasis, and LXR ؊ / ؊ -defi cient male mice have already been shown to have reduced fertility at an age of 5 months and complete sterility for 9-month-old animals. This sterility phenotype is associated with testes and caput epididymides epithelial defects. The research presented here was aimed at investigating how LXRs act in the male caput epididymidis by analyzing key actors in cholesterol homeostasis. We show that accumulation of cholesteryl esters in LXR The epididymis is an essential organ for reproductive physiology as sperm cells start the process of posttesticular maturation during their transit in this or...

“…The majority of nutrients for spermatogenesis, including lipids, are provided by the supporting Sertoli cells, which have the capacity to synthesize cholesterol from acetate in vitro ( 27 ). Because the cholesterol required to support spermatogenesis exceeds the biosynthetic capacity in Sertoli cells, cholesterol could be imported from circulation via specialized cholesterol transporters ( 28 ). Sertoli cells mainly depend on cholesterol acquired from HDLs by the apoE-dependent pathway ( 29,30 ).…”

Section: Discussionmentioning

confidence: 99%

Male germ cell-specific knockout of cholesterogenic cytochrome P450 lanosterol 14α-demethylase (Cyp51)

Keber

Ačimovič

Majdič

et al. 2013

sexes have been a matter of intense investigation. Early experiments suggested that a diffusible, sex-unspecifi c meiosis-inducing substance is produced by gonads of both sexes but induces meiotic initiation only in female germ cells. It was suggested that meiosis in the prespermatogonia could be blocked by the antagonistic action of meiosis-preventing substance, secreted by testicular cords ( 1, 2 ). In 1995, two structurally related sterols, termed meiosis-activating sterols (MAS), with the ability to trigger the resumption of meiosis in mouse oocytes cultured in vitro, were identifi ed ( 3 ). Follicular fl uid meiosis-activating sterol (FF-MAS), isolated from human follicular fl uid, and testis meiosis-activating sterol (T-MAS), isolated from bull testes, were the fi rst reported sterol precursors with potential biological activity and the fi rst compounds with meiosis-activating potency. Based on the sex-and species-unspecifi c action of MAS, a hypothesis about the important role of MAS in reproduction emerged ( 3, 4 ). However, follow-up in vitro experiments have provided evidence that MAS might not be absolutely essential for gonadotropin-mediated resumption of meiosis ( 5 ). In contrast, some studies have demonstrated that MAS and related analogs promote nuclear and cytoplasmic maturation of oocyte in vitro ( 6 ). Therefore, despite the existence of a relatively large body of in vitro studies indicating an important regulatory role of MAS in the onset of meiosis in oocytes, in vivo proof has not yet been provided. a Young Scientist Fellowship to R. K.; Abstract