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Effect of Prediabetes on Membrane Bicarbonate Transporters in Testis and Epididymis

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Abstract

The formation of competent spermatozoa is a complex event that depends on the establishment of adequate environments throughout the male reproductive tract. This includes the control of bicarbonate (HCO3 −) concentration, which plays an essential role in the maintenance of extracellular and intracellular pH (pHi) values. Diabetes mellitus alters pHi regulation in mammalian cells, mainly by altering the activity of ion transporters, particularly HCO3 −-dependent mechanisms. Yet, little is known about the effects of this pathology and its prodromal stage, prediabetes, on the membrane transport mechanisms of male reproductive tract cells. Herein, we analyzed protein and mRNA levels of the most relevant HCO3 − transporters of the SLC4 family [anion exchanger 2 (AE2), Na+-driven Cl−/HCO3 − exchanger (NDCBE), electrogenic Na+/HCO3 − cotransporter 1 (NBCe1), electroneutral Na+/HCO3 − cotransporter 1 (NBCn1)] in the testis and epididymis of a prediabetic animal model. Firstly, we identified the HCO3 − transporters of the SLC4 family, in both testicular and epididymal tissue. Secondly, although no alterations were detected in protein expression, mRNA levels of NBCe1, NBCn1 and NDCBE were significantly increased in the testis of prediabetic rats. On the other hand, in the epididymis, prediabetes caused an increase of AE2 and a decrease of NDCBE protein levels. These alterations may be translated into changes of HCO3 − transepithelial epididymal fluxes in vivo, which may represent a threat for sperm survival. Moreover, these results provide evidence of the molecular mechanism that may be responsible for the significant increase in abnormal sperm morphology already reported in prediabetic rats.

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Fig. 1
Fig. 2

Abbreviations

AE2:

Anion exchanger 2

BTB:

Blood–testis barrier

DM:

Diabetes mellitus

HED:

High energy diet

NBCe1:

Electrogenic Na+/HCO3 − cotransporters

NBCn1:

Electroneutral Na+/HCO3 − cotansporters

NDCBE:

Na+ driven Cl−/HCO3 − exchanger

pHi :

Intracellular pH

qPCR:

Real-time PCR

SLC4:

Solute carrier 4

STF:

Seminiferous tubular fluid

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

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Acknowledgments

This work was supported by the Fundação para a Ciência e a Tecnologia (PTDC/QUI-BIQ/121446/2010 and PEst-C/SAU/UI0709/2011), cofunded by Fundo Europeu de Desenvolvimento Regional via Programa Operacional Factores de Competitividade. M. G. A. (SFRH/BPD/80451/2011) was funded by the FCT. P. F. O. was funded by the FCT through FSE and POPH funds (Programa Ciência 2008).

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Authors and Affiliations

  1. CICS – UBI – Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilha, Portugal

    Raquel L. Bernardino, Ana D. Martins, Sílvia Socorro, Marco G. Alves & Pedro F. Oliveira

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  1. Raquel L. Bernardino
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  2. Ana D. Martins
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  3. Sílvia Socorro
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  4. Marco G. Alves
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  5. Pedro F. Oliveira
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Correspondence to Pedro F. Oliveira.

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Bernardino, R.L., Martins, A.D., Socorro, S. et al. Effect of Prediabetes on Membrane Bicarbonate Transporters in Testis and Epididymis. J Membrane Biol 246, 877–883 (2013). https://doi.org/10.1007/s00232-013-9601-4

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