Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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(-/-)-deficient 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(-/-) male mice is associated with a specific loss of ABCA1 and an increase in apoptosis of apical cells of the proximal caput epididymidis. ATP-binding cassette G1 (ABCG1) and scavenger receptor B1 (SR-B1), two other cholesterol transporters, show little if any modifications. Our study also revealed that SR-B1 appears to have a peculiar expression pattern along the epididymal duct. These results should help in understanding the functional roles of LXR in cholesterol trafficking processes in caput epididymidis.
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PMID:LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell-specific manner. 1939 34

Oxysterol nuclear receptors liver x receptors (LXRalpha and LXRbeta) regulate lipid homeostasis when cells have to face high amounts of cholesterol and/or fatty acids. Male mice invalidated for both lxr (LXR-/-) are infertile by 5 months of age, and become sterile by the age of 9 months. The epididymis was previously shown to be affected by the gene invalidation, a phenotype specifically located in the two proximal segments of this organ. We demonstrate here that cholesteryl esters are accumulated in a specific cell type of the epididymal epithelium, the apical cells, in these two first segments, in LXR-/- male mice. These accumulations are correlated to a decrease in the amount of a specific membrane cholesterol transporter, ATP-binding cassette A1 (ABCA1) in the caput epididymidis of LXR-/- mice. This decrease is due to a transcriptional down-regulation, and we further demonstrate that ABCA1, in the two first segments of the caput epididymidis, is located in the apical cells, and that its accumulation is lost in these cells for LXR-/- male mice as soon as 4 months of age. These data bring new elements in the cholesterol trafficking pathways in the epididymis, and will help a better understanding of the molecular mechanisms occurring in this organ in relation to the sperm cells maturation process.
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PMID:LXR regulate cholesterol homeostasis in the proximal mouse epididymis. 2006 98

It has been reported that following administration, alkylphenols, such as octylphenol, reach the testis and epididymis but fail to accumulate in these tissues, suggesting the rapid expulsion of these chemicals by transporters. Specialized transporters that function to restrict compounds that enter target cells have been identified. ABCB1 is a member of the ATP-binding cassette family of proteins capable of transporting a broad range of drugs and xenobiotics out of tissues. The objective of this study was to characterize the expression profile and functional role of ABCB1a and ABCB1b along the different regions (initial segment, caput, corpus [CS], and cauda [CA]) of the adult rat epididymis. ABCB1a and ABCB1b transcripts were detected in all four regions of the epididymis. Immunolocalization revealed minimal ABCB1 staining in epithelial cells or spermatozoa of proximal regions of the epididymis; however, this progressively increased in the CS and CA epididymis. This expression gradient was confirmed by Western blot, suggesting that spermatozoa acquire ABCB1 during epididymal maturation. Multidrug resistance (MDR) assays revealed that rat epididymal cells and epididymal spermatozoa display an MDR phenotype that can be inhibited under control conditions. To assess whether or not the system was inducible by alkylphenols, cells from an immortalized epididymal cell line (RCE) were exposed to different concentrations of nonylphenol. Results revealed a significant induction of both ABCB1a and ABCB1b messenger RNA and ABCB1 protein in RCE cells. Our findings demonstrate a role for ABCB1 in protecting both epididymal principal cells and spermatozoa from xenobiotics.
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PMID:Regulation and characterization of the ATP-binding cassette transporter-B1 in the epididymis and epididymal spermatozoa of the rat. 2096 54

During their epididymal maturation, stabilizing factors such as cholesterol sulfate are associated with the sperm plasma membrane. Cholesterol is sulfated in epididymal spermatozoa by the enzyme estrogen sulfotransferase. Because of its role in the efflux of sulfate conjugates formed intracellularly by sulfotransferases, the ATP-binding cassette membrane transporter G2 (ABCG2) might have a role in the translocation of this compound across the plasma membrane. In the present study we showed that ABCG2 is present in the plasma membrane overlaying the acrosomal region of spermatozoa recovered from testis, epididymis, and after ejaculation. Although ABCG2 is also present in epididymosomes, the transporter is not transferred to spermatozoa via this mechanism. Furthermore, although epididymal sperm ABCG2 was shown to be functional, as determined by its ability to extrude Hoechst 33342 in the presence of the specific inhibitor Fumitremorgin C, ABCG2 present in ejaculated sperm was found to be nonfunctional. Additional experiments demonstrated that phosphorylation of ABCG2 tyrosyl residues, but not its localization in lipid rafts, is the mechanism responsible for its functionality. Dephosphorylation of ABCG2 in ejaculated spermatozoa is proposed to cause a partial protein relocalization to other intracellular compartments. Prostasomes are proposed to have a role in this process because incubation with this fraction of seminal plasma induces a decrease in the amount of ABCG2 in the associated sperm membrane fraction. These results demonstrate that ABCG2 plays a role in epididymal sperm maturation, but not after ejaculation. The loss of ABCG2 function after ejaculation is proposed to be regulated by prostasomes.
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PMID:ATP-binding cassette transporter G2 activity in the bovine spermatozoa is modulated along the epididymal duct and at ejaculation. 2244 96