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18 May 2011 Swine Models of Cystic Fibrosis Reveal Male Reproductive Tract Phenotype at Birth
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Abstract

Nearly all male cystic fibrosis (CF) patients exhibit tissue abnormalities in the reproductive tract, a condition that renders them azoospermic and infertile. Two swine CF models have been reported recently that include respiratory and digestive manifestations that are comparable to human CF. The goal of this study was to determine the phenotypic changes that may be present in the vas deferens of these swine CF models. Tracts from CFTR−/− and CFTRΔF508/ΔF508 neonates revealed partial or total vas deferens and/or epididymis atresia at birth, while wild-type littermates were normal. Histopathological analysis revealed a range of tissue abnormalities and disruptions in tubular organization. Vas deferens epithelial cells were isolated and electrophysiological results support that CFTR−/− monolayers can exhibit Na reabsorption but reveal no anion secretion following exposure to cAMP-generating compounds, suggesting that CFTR-dependent Cl and/or HCO3 transport is completely impaired. SLC26A3 and SLC26A6 immunoreactivities were detected in all experimental groups, indicating that these two chloride-bicarbonate exchangers were present, but were either unable to function or their activity is electroneutral. In addition, no signs of increased mucus synthesis and/or secretion were present in the male excurrent ducts of these CF models. Results demonstrate a causal link between CFTR mutations and duct abnormalities that are manifested at birth.

Vas deferens and epididymis abnormalities are present in pigs lacking the cystic fibrosis transmembrane conductance regulator at birth.

Fernando Pierucci-Alves, Vladimir Akoyev, Jimmie C. Stewart, Lin-Hua Wang, Kyathanahalli S. Janardhan, and Bruce D. Schultz "Swine Models of Cystic Fibrosis Reveal Male Reproductive Tract Phenotype at Birth," Biology of Reproduction 85(3), 442-451, (18 May 2011). https://doi.org/10.1095/biolreprod.111.090860
Received: 5 January 2011; Accepted: 1 April 2011; Published: 18 May 2011
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