Regulation of epithelial function, differentiation, and remodeling in the epididymis

Breton, Sylvie; Ruan, Ye Chun; Park, Yoo‑Jin; Kim, Bongki

doi:10.4103/1008-682x.165946

Cited by 86 publications

(89 citation statements)

References 93 publications

(153 reference statements)

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“…In support of SLC26A3 anion exchange activity within the epididymal epithelium, we found abnormal distribution and increased amount of V ATPase protein in SLC26A3 epididymides, which reflect bicarbonate and pH deregulation within the luminal fluid, as plasma membrane targeting and proton pump activity of the V‐ATPase were reported to be regulated by bicarbonate (Breton et al, ; Shum et al, , ). In addition, SLC26A3 deficient cauda, exhibit an excessive increase of acrosome‐deficient sperm cells and some morphological anomalies of the flagellum, such as hairpin‐like bending and coiled flagellum, which were described to be induced by osmotic deregulation (Yeung et al, ; Yeung, Barfield, & Cooper, , ).…”

Section: Discussionsupporting

confidence: 66%

“…In particular, segment 1 of the caput, showed increased V‐ATPase staining at the apical pole of the cells; in addition, narrow/clear cells from segment 2, which were merely stained in wild‐type epididymides, displayed increased V‐ATPase staining in the mutant (Figure b). Such increase in V‐ATPase staining would be consistent with a dysregulation of luminal bicarbonate concentration and/or acidification in SLC26A3‐deficient epididymides, as V‐ATPase targeting at the plasma membrane within clear cells was shown to be regulated by bicarbonate and pH (Breton, Ruan, Park, & Kim, ; Shum, Da Silva, Brown, & Breton, ; Shum, Ruan, da Silva, & Breton, ).…”

Section: Resultsmentioning

confidence: 77%

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Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse

Khouri

Whitfield

Stouvenel

et al. 2018

Molecular Reproduction Devel

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Members of the solute carrier 26 (SLC26) family have emerged as important players in mediating anions fluxes across the plasma membrane of epithelial cells, in cooperation with the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Among them, SLC26A3 acts as a chloride/bicarbonate exchanger, highly expressed in the gastrointestinal, pancreatic and renal tissues. In humans, mutations in the SLC26A3 gene were shown to induce congenital chloride-losing diarrhea (CLD), a rare autosomal recessive disorder characterized by life-long secretory diarrhea. In view of some reports indicating subfertility in some male CLD patients together with SLC26-A3 and -A6 expression in the male genital tract and sperm cells, we analyzed the male reproductive parameters and functions of SLC26A3 deficient mice, which were previously reported to display CLD gastro-intestinal features. We show that in contrast to Slc26a6, deletion of Slc26a3 is associated with severe lesions and abnormal cytoarchitecture of the epididymis, together with sperm quantitative, morphological and functional defects, which altogether compromised male fertility. Overall, our work provides new insight into the pathophysiological mechanisms that may alter the reproductive functions and lead to male subfertility in CLD patients, with a phenotype reminiscent of that induced by CFTR deficiency in the male genital tract.

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Section: Discussionsupporting

confidence: 66%

Section: Resultsmentioning

confidence: 77%

Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse

Khouri

Whitfield

Stouvenel

et al. 2018

Molecular Reproduction Devel

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“…The epididymal epithelium consists of different cell types including principal, narrow, clear, and basal cells that work together to establish an optimal environment. Narrow cells in the initial segment and clear cells (CCs) in the caput, corpus, cauda (Cd), and vas deferens secrete protons via the proton-pumping vacuolar (V-ATPase) located in their apical membrane [3,5,[11][12][13]. The V-ATPase is a major contributor to luminal acidification in several organs, including the kidney, airway, and osteoclast, in addition to the epididymis [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Park¹,

Battistone²,

Kim³

et al. 2017

Biology of Reproduction

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While spermatozoa undergo epididymal maturation, they remain quiescent thanks to the establishment of a low luminal pH. This study is aimed at determining how epithelial cells lining the epididymal lumen work together to maintain and regulate this acidic milieu. In particular, we examined the relative contribution of clear cells (CCs) and principal cells (PCs) to this process. Functional analysis in the mouse cauda epididymidis (Cd) perfused in vivo showed that the pH of a control solution remained constant at pH 6.6 after perfusion through the Cd lumen. In contrast, the pH of both an acidic (pH 5.8) and alkaline (pH 7.8) perfusate was progressively restored toward the control acidic pH. Pharmacological studies indicated the contribution of cystic fibrosis transmembrane regulator, previously shown to be present in the apical membrane of PCs, to the recovery from an acidic pH of 5.8. In addition, we found that CCs and PCs equally contribute to the recovery from an alkaline of 7.8, via the H + pumping vacuolar ATPase (V-ATPase) located in CCs, and the Na + /H + exchanger type 3 (NHE3) located in PCs. Immunofluorescence labeling showed apical membrane accumulation of the V-ATPase in CCs at pH 7.8, and its internalization at pH 5.8 compared to pH 6.6. Immunofluorescence showed expression of NHE3, but absence of NHE2, in PCs located in the Cd. RT-PCR and western blotting showed expression of NHE3 in all epididymal regions. Luminal 8-(4-chlorophenylthio)adenosine 3 ,5 -cyclic monophosphate (cpt-cAMP) partially inhibited luminal pH recovery from pH 7.8. However, cpt-cAMP induced an increase in V-ATPase apical membrane accumulation at this pH. Cell fractionation studies showed the apical accumulation of NHE3 from intracellular vesicles at pH 7.8 versus 6.6, and prevention of this effect by cpt-cAMP. These results indicate the participation of both CCs and PCs in the regulation of luminal pH in the epididymis. Our study also shows the dual role of PCs in HCO 3 − and H + secretion, and that this switch from base to acid secretion depends on the luminal environment. Characterization of the respective roles of CCs and PCs in the regulation of the optimal luminal condition for epididymal sperm maturation should provide new frameworks for the evaluation and treatment of male infertility. Summary SentenceThis study shows the equal contribution of clear and principal cells to proton secretion, and the dual role of principal cells in bicarbonate and proton secretion, depending on luminal cues.

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“…N and C cells are secreting cells of protons and are implicated in luminal acidification (Arrighi, Ventriglia, et al., ; Da Silva et al., ). Acidification of luminal pH and low bicarbonate concentration may contribute to the maintenance of sperm in a dormant state during maturation and storage in the epididymis (Breton, Ruan, Park, & Kim, ; Da Silva et al., ; Shum, Ruan, Silva, & Breton, ), which may explain the AQP9 expression by the N cell.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 9 is expressed in the epididymis of immature and mature pigs

Schimming

Baumam

Pinheiro

et al. 2017

Reprod Domestic Animals

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Aquaporins (AQPs) are channel proteins that facilitate the transepithelial and bidirectional movement of water. AQP9 is an aquaporin that is expressed in the mammalian epididymis. This water transport contributes to epididymal sperm concentration. This study aimed to examine the morphology of epididymal epithelium in piglets and boars, as well as the expression and immunolocalization of AQP9. The piglets presented an epididymal epithelium in differentiation with principal, basal and apical cells. The cellular population of the epididymal epithelium in boars consisted of principal, basal, apical, clear and narrow cells. The migratory cells known as halo cells were observed in the epididymis of both piglets and boars. AQP9 expression presented differences between piglets and boars. Moderate intensity of AQP9 immunoreaction was observed in the apical border of the epididymal epithelium of the caput and cauda regions in the piglet epididymis. A moderate-to-intense reaction for AQP9 was observed in the nuclei of epithelial cells of the three epididymal regions in the boar epididymis. The region of the cauda epididymis showed reactivity for AQP9 also in the apical border of the epithelium. It is believed that the AQP9 is already functional in piglets at only 1 week of age and is more active, playing a pivotal role in the caput and cauda regions of the epididymis. Moreover, the intense AQP9 expression in the apical border of epithelial cells in the cauda region of the boar epididymis suggests a higher performance of AQP9 in this region, where sperm complete their maturation process, stored and concentrated.

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Regulation of epithelial function, differentiation, and remodeling in the epididymis

Cited by 86 publications

References 93 publications

Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse

Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse

Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Aquaporin 9 is expressed in the epididymis of immature and mature pigs

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