The epididymis is a single and highly convoluted tubule system in mammals. The epithelium is the major compartment for epididymal function. Proteins synthesized and secreted by epididymal epithelium provide a special and ever-changing luminal fluid environment for sperm as they progress through the epididymis, which makes sperm achieve motility and ultimately results in sperm functional maturation. Specialized genes expressed in the epididymis have regional-specific characteristics. They are regulated by androgen and/or testicular factors and present spatial and tempel-specialized expression pattern in postnatal development, all these hint that they play important and unique roles in epididymis.
Animals ; Epididymal Secretory Proteins ; genetics ; Epididymis ; physiology ; Gene Expression Regulation, Developmental ; Male ; Mammals ; Sperm Maturation ; genetics

OBJECTIVETo identify the specific protein in the epididymal luminal fluid that may play a role in sperm epididymal maturation or modification on the surface of spermatozoa.

METHODSWe compared the differential protein components in the lumen fluids from the caput and cauda segments of the epididymis of normal rats as well as from the cauda segment of experimental left varicocele (ELV) rats by SDS-PAGE or 2D-electrophoresis. The protein spots of interest were selected for MS identification, and the target proteins further characterized by immuno-blot assay.

RESULTSMS analysis showed that one of the most prominent proteins, M(r) 22 000, was identical to the phosphatidylethanolamine-binding protein (PBP), and it was further identified as PBP by immuno-blot assay.

CONCLUSIONPBPs were present in a variety of molecular forms in the epididymal luminal fluid, including the glycosylated form, and ELV markedly elevated the PBP level in the cauda luminal fluid of the rats. Thus, the association of this molecule with sperm surface modification remains an interest for future investigation.

Animals ; Disease Models, Animal ; Epididymal Secretory Proteins ; isolation & purification ; Epididymis ; metabolism ; Male ; Rats ; Varicocele ; metabolism

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.
Biomarkers, Tumor ; Epididymal Secretory Proteins ; Humans* ; Immunoassay ; Lung Diseases ; Lung Neoplasms* ; Lung* ; Lymph Nodes ; Male ; Neoplasm Metastasis ; ROC Curve

Sperm maturation in the epididymis is regulated by changes of luminal ion concentration and processing of sperm surface membrane by several glycosidases and proteases, and the actions of the proteases are controlled by protease inhibitors present in specific areas of the epididymis. WFDC-type serine protease inhibitors that are highly expressed in the epididymis play an important role in natural immunity and male reproduction. This paper gives an overview of the structure and function of the protein and its application prospects in the development of drugs for male reproductive tract infection and immunocontraception.
Anti-Infective Agents ; therapeutic use ; Contraceptive Agents ; Epididymal Secretory Proteins ; metabolism ; Epididymis ; chemistry ; metabolism ; Humans ; Male ; Serine Proteinase Inhibitors ; genetics ; metabolism ; therapeutic use

BACKGROUNDHuman epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown.

METHODSIn this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro.

RESULTSHE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro.

CONCLUSIONHE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion.

Biomarkers, Tumor ; analysis ; Cell Line, Tumor ; Disease Progression ; Epididymal Secretory Proteins ; analysis ; genetics ; physiology ; Female ; Gene Silencing ; physiology ; Humans ; Ovarian Neoplasms ; pathology ; RNA Interference

AIMIdentification of the rodent counterparts of human and canine epididymal cDNAs HE3, HE4 and Ce8/Ly6G5C by sequence homology and analysis of their expression patterns and regulation level in the rat.

METHODS"Electronic screening" of Expressed Sequence Tag (EST) and genomic databases, followed by RT-PCR and Northern blot analysis.

RESULTSRodent ESTs and genomic sequences homologous to HE3, HE4 and Ce8/Ly6G5C were identified in the public databases and the "full-length" rat cDNAs cloned. To emphasise their homology to the human and canine genes, they were named Me3/Re3, Me4/Re4 and Re8 for mouse and rat counterparts, respectively. mRNA expression patterns were analysed in rats, including rat HE1 and HE5/CD52 counterparts as controls. Re3 and Re8 mRNAs were only found in the rat epididymis, while Re4 showed a broader tissue distribution. Within the epididymis, Re3 and Re4 mRNAs were detected in all regions; Re8, on the other hand, was restricted to the caput. During postnatal development, Re3 and control mRNAs were found from the earliest stages investigated, while Re8 mRNA was observed only from day 24 postnatum, corresponding to the onset of spermatogenesis in the prepubertal testis. Castration and testosterone supplementation of adult male rats suggested that none of the cloned mRNAs was directly androgen-regulated. Efferent duct ligation, however, showed that Re8 mRNA levels depended on testicular factors other than androgens.

CONCLUSIONThe novel rodent cDNAs can now be used to monitor epididymal gene expression more closely and to set up various regulatory and functional studies.

Amino Acid Sequence ; Animals ; Blotting, Northern ; Carrier Proteins ; chemistry ; genetics ; DNA, Complementary ; chemistry ; Dogs ; Epididymal Secretory Proteins ; chemistry ; genetics ; Epididymis ; chemistry ; Glycoproteins ; chemistry ; genetics ; Humans ; Male ; Molecular Sequence Data ; Proteins ; chemistry ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology ; Tissue Distribution ; beta-Defensins