Polarized Distribution of NHE1 and NHE2 in the Rat Epididymis

Chew, Sek-Jin; Leung, George P.H.; Leung, P. Y.; Tse, Chung Ming; Wong, Patrick

doi:10.1095/biolreprod62.3.755

Cited by 33 publications

(32 citation statements)

References 18 publications

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“…These proteins serve important functions in regulating intracellular pH, cell volume, acid-base balance, and neutral NaCl absorption (43,44). NHE8 joins NHE1, NHE2, NHE3, and NHE10 as NHE isoforms detected in the testis (6,14,38). Previously, we detected NHE8 mRNA in human testis (unpublished observation), and others detected NHE8 mRNA in mouse testis (12).…”

Section: Discussionmentioning

confidence: 78%

“…NHE1, a ubiquitously expressed isoform, is detected in virtually all cell types in the testis. NHE2 and NHE3 are expressed on the apical membrane of epithelial cells in the efferent and epididymal ducts (6,14,29,46). NHE8 mRNA was detected in mouse testis (12).…”

mentioning

confidence: 99%

“…NHE10 is a spermatozoa-specific NHE isoform (38). Of these NHEs, only the functions of NHE3 and NHE10 were known to directly affect male fertility (6,24,38). The testes of mice lacking NHE3 have increased fluid volume, so sperm concentration was diminished, which leads to subfertility (46).…”

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confidence: 99%

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Disruption of NHE8 expression impairs Leydig cell function in the testes

Chen

et al. 2015

American Journal of Physiology-Cell Physiology

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Multiple sodium/hydrogen exchanger (NHE) isoforms are expressed in the testes, and they play various roles in cell volume regulation, intracellular pH regulation, and fluid absorption. NHE8, the most recently characterized NHE family member, is detected in the Leydig cells in humans and mice in great abundance by immunohistochemistry in the current study. Male mice lacking NHE8 expression were infertile. Despite having intact male reproductive organs, male NHE8 Ϫ/Ϫ mice have smaller testes and lacked spermatozoon in the seminiferous tubules and the epididymis. At the age of 39 wk, few spermogonia were seen in the testis in NHE8 Ϫ/Ϫ mice. Although male NHE8 Ϫ/Ϫ mice have normal serum levels of luteinizing hormone and follicle-stimulating hormone, serum testosterone level was significantly reduced. These mice have decreased expression of luteinizing hormone receptor in the testes. In NHE8 small-interfering RNA-transfected mouse Leydig cells (MLTC-1), silencing of NHE8 decreased the expression of luteinizing hormone receptor by ϳ70%. Moreover, loss of NHE8 function in Leydig cells resulted in disorganized luteinizing hormone receptor membrane distribution. Therefore, male infertility in NHE8 Ϫ/Ϫ mice is at least partially due to the disruption of luteinizing hormone receptor distribution and consequent low testosterone production, which leads to Sertoli cell dysfunction. Our work identified a novel role of NHE8 in male fertility through its effect on modifying luteinizing hormone receptor function.

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Section: Discussionmentioning

confidence: 78%

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confidence: 99%

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Disruption of NHE8 expression impairs Leydig cell function in the testes

Chen

et al. 2015

American Journal of Physiology-Cell Physiology

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“…Na + transportation is actively linked to H + secretion and fluid reabsorption (Wong and Yeung et al, 1978;Chew et al, 2000). Immunofluorescence showed that the Na + -K + -ATPase 1 subunit, NHE3 and Aqp9 were markedly reduced in the efferent ducts and caput epididymis in adult Gpr48 -/-mice ( Fig.…”

Section: Reduced Expression Of Water and Ion Transporters In Reproducmentioning

confidence: 94%

G protein-coupled receptor 48 upregulates estrogen receptor α expression via cAMP/PKA signaling in the male reproductive tract

Sun

et al. 2010

Development

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SUMMARYThe epididymis and efferent ducts play major roles in sperm maturation, transport, concentration and storage by reabsorbing water, ions and proteins produced from seminiferous tubules. Gpr48-null male mice demonstrate reproductive tract defects and infertility. In the present study, we found that estrogen receptor  (ER) was dramatically reduced in the epididymis and efferent ducts in Gpr48-null male mice. We further revealed that ER could be upregulated by Gpr48 activation via the cAMP/PKA signaling pathway. Moreover, we identified a cAMP responsive element (Cre) motif located at -1307 to -1300 bp in the ER promoter that is able to interact with Cre binding protein (Creb). In conclusion, Gpr48 participates in the development of the male epididymis and efferent ducts through regulation of ER expression via the cAMP/PKA signaling pathway. KEY WORDS: Gpr48, ER(Esr1), Creb, Epididymis, Infertility, MouseG protein-coupled receptor 48 upregulates estrogen receptor  expression via cAMP/PKA signaling in the male reproductive tract DEVELOPMENT 152 is observed in Gpr48-null mice. The expression of ER, NHE3 and aquaporin 1 (Aqp1) is reduced in the proximal segment of the efferent ducts.In the present study, we investigated the role of Gpr48 in the regulation of ER expression and further explored the molecular mechanism underlying this regulation. MATERIALS AND METHODS MiceGpr48-null male mice were housed at 21±1°C with a humidity of 55±10% and a 12-hour light-dark cycle. Food and water were available ad libitum. For genotyping analysis, genomic DNA was isolated from tail biopsy and PCR was carried out using three primers: upstream primer 5Ј-CCAGTCACCACTCTTACACAATGGCTAAAC-3Ј; and downstream primers 5Ј-GGTCTTTGAGCACCAGAGGAC-3Ј and 5Ј-TCCCGTAG -GAGATAGCGTCCTAG-3Ј. With regard to the male fertility assay, each Gpr48+/-and Gpr48 -/-adult male aged 12 weeks was housed with two Gpr48 +/+ females. The females were examined daily for vaginal plugs. The litter number was counted immediately after parturition. The animal protocol was reviewed and approved by the Animal Care Committee of Shanghai Jiao Tong University School of Medicine. Ligation operationTwenty-four mice at 3 weeks of age received bilateral efferent ductile ligation (EGL; n8), bilateral vasoligation (VGL; n8) and sham operations (n8). For EGL, the efferent ductule was doubly ligated close to the epididymis and away from the epididymal and testicular vasculature and vas deferens. For VGL, bilateral vasa deferentia were doubly ligated. The mice receiving EGL, VGL or sham operations were observed daily to ascertain a normal descending of the testes. Immunofluorescence and immunohistochemical stainingAnimal tissues were fixed overnight in Bouin's solution, dehydrated in ethanol, embedded in paraffin and sectioned at 5 m. Immunofluorescence and immunohistochemical staining were performed according to a standard protocol. In brief, the sections were de-paraffined, progressively rehydrated and treated with 3% hydrogen peroxide in methanol for 30 minutes...

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“…Different sets of transporters, expressed in specific cell types in different segments of the epididymal tubule, participate in the progressive decrease in bicarbonate concentration and pH that occurs as the fluid flows through the lumen of the epididymis (reviewed by Da Silva et al, 2007b;Pastor-Soler et al, 2005). Significant bicarbonate reabsorption occurs in the initial segments and caput of the epididymis (Levine and Kelly, 1978;Levine and Marsh, 1971) via the sodium-hydrogen exchangers NHE2 and NHE3 (Bagnis et al, 2001;Cheng Chew et al, 2000) located in the apical membrane of principal cells, and the basolateral anion exchanger AE2 (Jensen et al, 1999b) and sodium-bicarbonate cotransporter NBC-e1 (also known as SLC4A4) (Jensen et al, 1999a). Clear cells, which express high levels of the vacuolar proton pumping ATPase, V-ATPase, are involved in luminal acidification in the distal epididymis (Breton et al, 1996;Brown et al, 1992;Herak-Kramberger et al, 2001;Pietrement et al, 2006).…”

Section: Introductionmentioning

confidence: 99%