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Testicular lumicrine factors regulate ERK, STAT and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis

ABSTRACT: The initial segment of the epididymis is vital for male fertility, therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from epididymis, a subset of cells within the initial segment undergo apoptosis. In this study, microarray analyses was used to examine early changes in the downstream signal transduction pathways following the loss of lumicrine factors, and we discovered the following cascade of events leading to loss of protection and eventual apoptosis. First, mRNA expression of several key components of ERK pathway decreased sharply after 6 hours of loss protection from testicular lumicrine factors. After 12 hours, the levels of mRNA expression of STAT and NF-кB pathways components increased, mRNA expression of genes encoding cell cycle inhibitors increased. After 18 hours of loss protection from testicular lumicrine factors, apoptosis was observed in the initial segment. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating ERK pathway, repressing STAT and NF-кB pathways, and preventing a cascade of reactions leading to apoptosis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE21806 | GEO | 2011/03/11

SECONDARY ACCESSION(S): PRJNA126965

REPOSITORIES: GEO

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Testicular lumicrine factors regulate ERK, STAT and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis

Project description:The initial segment of the epididymis is vital for male fertility, therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from epididymis, a subset of cells within the initial segment undergo apoptosis. In this study, microarray analyses was used to examine early changes in the downstream signal transduction pathways following the loss of lumicrine factors, and we discovered the following cascade of events leading to loss of protection and eventual apoptosis. First, mRNA expression of several key components of ERK pathway decreased sharply after 6 hours of loss protection from testicular lumicrine factors. After 12 hours, the levels of mRNA expression of STAT and NF-кB pathways components increased, mRNA expression of genes encoding cell cycle inhibitors increased. After 18 hours of loss protection from testicular lumicrine factors, apoptosis was observed in the initial segment. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating ERK pathway, repressing STAT and NF-кB pathways, and preventing a cascade of reactions leading to apoptosis. Unilateral efferent duct ligation (EDL) surgeries were performed to block lumicrine testicular fluid factors from reaching one side of epididymis. For the control, a sham operation was performed on the contra-lateral side within the same animal. After 6, 12 and 18 hours of EDL, the most proximal region of the initial segment containing zone 1a and 1b of initial segment was dissected out. In this microarray study, sham control and each time point of EDL (sham, 6h EDL, 12h EDL, 18h EDL) all have 4 replicates, a total of 16 arrays were hybridized.

2011-03-11 | E-GEOD-21806 | biostudies-arrayexpress

Rattus norvegicus

Project description:Testicular lumicrine factors regulate ERK, STAT and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis

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PTEN is essential in the maintenance of normal transporter activity in the epididymal epithelium

Project description:A fully developed initial segment, the most proximal region of the epididymis, is important for male fertility. Conditional deletion of Pten from the initial segment from postnatal day 17 onwards resulted in de-differentiation of the initial segment. When spermatozoa progressed through the de-differentiated epididymal duct, they developed angled flagella, suggesting compromised sperm maturation, which eventually resulted in male infertility. To understand mechanisms that underlie this sperm maturation defect following loss of Pten, we compared transcriptome profile of the initial segment between controls and knockouts and revealed that the transporter activity was one of the top molecular and cellular functions altered following loss of Pten. Alteration in the protein levels and localization of several transporters following loss of Pten were also observed by immunofluorescence analysis. Epithelial cells of the initial segment from knockouts are more permeable to Fluorescein isothiocyanate-dextran (4000da) compared to controls. When analyzing GEO datasets with Pten deletion in the prostate and inner ear of mice, alteration in transporter activity was also found in these Pten knockout mouse models, suggesting it is a common phenomenon. PTEN regulates transporter activities probably through regulation of cell shape, size, and membrane property, which in turn regulates the intracellular and intercellular micro-environment.

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RNA sequencing analysis of Ovch2 knockout initial segment-caput epididymis.

Project description:Purpose: The purpose of this study is to characterize gene expression in the Ovch2-ablated mouse initial segment (IS)-caput epididymis. Methods: Ovch2-/- mice were used when they were 14-week-old. IS-caput epididymal mRNA profiles were generated by deep sequencing, in triplicate, using Illumina NovaSeq6000. Results: RNA-seq data identified differentially expressed transcripts. Conclusions: Our results show that the expression of many genes was not critically affected by Ovch2 ablation.

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Project description:The testis, efferent ductules, epididymis, and vas deferens, constituting the majority of male reproductive tract, are the regions for testosterone production, spermatogenesis, and sperm maturation, storage and discharge, but whether these regions change during aging is unknown. Here, we addressed this by investigating the adult (3-month) and aged (18-month) transcriptomes from seven regions of male mouse reproductive tract：the testis, efferent ductules, initial segment, caput, corpus and cauda epididymis, and vas deferens. We identified various of region-specific genes across different regions of male mouse reproductive tract. Moreover, we identified region-dependent changes of transcripts at an anatomic resolution. This study provides a framework for futher studies on male reproducitve aging.

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Extracellular vesicles are involved in the paracrine communication between epithelial cells in different regions of the domestic cat epididymis

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