Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions

Browne, James A.; Yang, Rui; Leir, Shih Hsing; Eggener, Scott E.; Harris, Ann

doi:10.1093/molehr/gav066

Cited by 70 publications

(115 citation statements)

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“…Attached along the caudomedial border of the testis, the epididymis can be divided into three main segments, the caput (head), corpus (body) and cauda (tail), which finally tapers into the vas deferens. It is through this tube that sperm progressively acquire functional competency for fertilisation, and therefore characteristic highly regionalised gene and protein expression profiles give rise to a dynamic intraluminal environment [14]. One particular β-defensin, (BD126) has been documented to play a number of roles critical to sperm survival, motility and interaction with the female reproductive tract and its secretions [15–17].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomic identification and validation of β-defensin genes in the Ovis aries genome

et al. 2017

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Backgroundβ-defensins are small, cationic, antimicrobial peptides found in species across the plant and animal kingdoms. In addition to microbiocidal activity, roles in immunity as well as reproduction have more recently been documented. β-defensin genes in Ovis aries (domestic sheep) have been poorly annotated, having been identified only by automatic gene prediction algorithms. The objective of this study was to use a comparative genomics approach to identify and characterise the β-defensin gene repertoire in sheep using the bovine genome as the primary reference.ResultsAll 57 currently predicted bovine β-defensin genes were used to find orthologous sequences in the most recent version of the sheep genome (OAR v4.0). Forty three genes were found to have close genomic matches (>70% similarity) between sheep and cattle. The orthologous genes were located in four clusters across the genome, with 4 genes on chromosome 2, 19 genes on chromosome 13, 5 genes on chromosome 20 and 15 genes on chromosome 26. Conserved gene order for the β-defensin genes was apparent in the two smaller clusters, although gene order was reversed on chromosome 2, suggesting an inversion between sheep and cattle. Complete conservation of gene order was also observed for chromosome 13 β-defensin orthologs. More structural differences were apparent between chromosome 26 genes and the orthologous region in the bovine reference genome, which is known to be copy-number variable. In this cluster, the Defensin-beta 1 (DEFB1) gene matched to eleven Bovine Neutrophil beta-Defensin (BNBD) genes on chromosome 27 with almost uniform similarity, as well as to tracheal, enteric and lingual anti-microbial peptides (TAP, EAP and LAP), suggesting that annotation of the bovine reference sequence is still incomplete. qPCR was used to profile the expression of 34 β-defensin genes, representing each of the four clusters, in the ram reproductive tract. Distinct site-specific and differential expression profiles were detected across the reproductive tract of mature rams with preferential β-defensin gene expression in the epididymis, recapitulating observations for orthologous genes in other species.ConclusionsThis is the first comprehensive analysis of β-defensin genes encoded by the ovine reference sequence, and the first report of an expanded repertoire of β-defensin genes in this species. The preferential expression of these genes in the epididymis suggests a role in fertility, possibly providing immunoprotection for sperm within the female reproductive tract.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3666-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Comparative genomic identification and validation of β-defensin genes in the Ovis aries genome

et al. 2017

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“…Many functional pathways in the human epididymis show regional distribution, with the caput epithelium being distinct from both the corpus and cauda, which are more similar (16). HNF1α and HNF1β protein levels in caput, corpus and cauda HEE cells were analyzed by western blot (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Though in an analysis of gene expression in intact epididymis tissue segments by microarray (14), neither HNF1α nor HNF1β showed a regional distribution, this likely reflects the minor contribution of the epithelium to the whole tissue gene expression profile. We previously showed that HNF1β is much more abundant than HNF1α throughout the epididymis epithelium, though both show strong regional expression (16). Here, we confirm by western blot that HNF1β is much more abundant than HNF1α in caput HEE cells and so our data primarily relate to the functions of HNF1β.…”

Section: Discussionmentioning

confidence: 99%

“…We recently showed that PAX2 coordinates gene expression in a human epididymis epithelial cell line (24). Of interest, PAX2 and PAX8 are, like HNF1, more abundant in the caput HEE cells than in corpus or cauda cells (16). HNF1 is part of the transcription factor complex that regulates expression of the CFTR gene in intestinal epithelial cells (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…Though the functions of HNF1α and HNF1β are well studied in epithelia from several other tissues (liver, kidney, intestine, and pancreas, reviewed in (12) their role in the adult epididymis epithelium remains unexplored. The human epididymis has 3 functionally distinct regions: the head (caput), body (corpus) and tail (cauda) with different transcriptomes (13-16). The caput and cauda luminal environments are probably the most relevant for sperm maturation (17,18).…”

Section: Introductionmentioning

confidence: 99%

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HNF1 regulates critical processes in the human epididymis epithelium

Browne¹,

Yang²,

Eggener

et al. 2016

Molecular and Cellular Endocrinology

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The luminal environment of the epididymis participates in sperm maturation and impacts male fertility. It is dependent on the coordinated expression of many genes encoding proteins with a role in epithelial transport. We identified cis-regulatory elements for critical genes in epididymis function, by mapping open chromatin genome-wide in human epididymis epithelial (HEE) cells. Bioinformatic predictions of transcription factors binding to the regulatory elements suggested an important role for hepatocyte nuclear factor 1 (HNF1) in the transcriptional program of these cells. Chromatin immunoprecipitation and deep sequencing (ChIP-seq) revealed HNF1 target genes in HEE cells. In parallel, the contribution of HNF1 to the transcriptome of HEE cells was determined by RNA-seq, following siRNA-mediated depletion of both HNF1α and HNF1β transcription factors. Repression of these factors caused differential expression of 1892 transcripts (902 were downregulated and 990 upregulated) in comparison to a non-targeting siRNA. Differentially expressed genes with HNF1 ChIP-seq peaks within 20kb were subject to gene ontology process enrichment analysis. Among the most significant pathways associated with down-regulated genes were epithelial transport of water, phosphate and bicarbonate, all critical processes in epididymis epithelial function. Measurements of intracellular pH (pHi) confirmed a role for HNF1 in regulating the epididymis luminal environment.

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Effects of a high‐fat diet on rat epididymis

et al. 2023

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The epididymis plays an essential role in reproduction, promoting sperm cell maturation. In this study, we investigated the effects of a high-fat diet (HFD) in the three regions of the epididymis of rats, including caput, corpus, and cauda. Our results showed an increase in malondialdehyde and a decrease in superoxide dismutase, which indicated an increase in oxidative stress in all segments of the epididymis. The cellular response mechanisms were mostly detected in the corpus/ cauda regions, which showed an increase in apoptosis, probably for eliminating dysfunctional cells arising from HFD-induced oxidative stress, and a decrease in mitophagy. Additionally, an increase in lipophagy to prevent lipid accumulation and a decrease in cell proliferation were recorded in the corpus.

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Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions

Abstract: This work was supported by the National Institutes of Health: R01HD068901 (PI: A.H.). The authors declare no conflict of interest.

Cited by 70 publications

References 59 publications

Comparative genomic identification and validation of β-defensin genes in the Ovis aries genome

Comparative genomic identification and validation of β-defensin genes in the Ovis aries genome

HNF1 regulates critical processes in the human epididymis epithelium

Effects of a high‐fat diet on rat epididymis

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