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The role of CFTR in male reproductio...

The Chinese University of Hong Kong (Hong Kong).

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The role of CFTR in male reproduction and the underlying mechanisms.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The role of CFTR in male reproduction and the underlying mechanisms./
Author:	Xu, Wenming.
Description:	138 p.
Notes:	Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4506.
Contained By:	Dissertation Abstracts International69-08B.
Subject:	Biology, Animal Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3326175
ISBN:	9780549774211

The role of CFTR in male reproduction and the underlying mechanisms.
Xu, Wenming.

The role of CFTR in male reproduction and the underlying mechanisms. - 138 p.

Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4506.

Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2008.

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl- and HCO3- transport. While over 95% of CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates.

ISBN: 9780549774211Subjects--Topical Terms:

1017835
Biology, Animal Physiology.

The role of CFTR in male reproduction and the underlying mechanisms.
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020 $a 9780549774211
035 $a (UMI)AAI3326175
035 $a AAI3326175
040 $a UMI $c UMI
100 1 $a Xu, Wenming. $3 1058932
245 1 4 $a The role of CFTR in male reproduction and the underlying mechanisms.
300 $a 138 p.
500 $a Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4506.
502 $a Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2008.
520 $a Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl- and HCO3- transport. While over 95% of CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates.
520 $a CFTR is known to be widely expressed in epithelial cells of male reproductive tracts, but its expression in spermatogenic cells is less well known. We first confirmed the expression of CFTR in spermatogenic cells and mature sperm in rodents. Our study thus focused on the important role of CFTR in the processes related to male fertility including spermatogenesis and sperm capacitation.
520 $a As CFTR plays an important role in HCO3- transport, and HCO3- sensitive soluble adenylyl cyclase (sAC) has been shown to be largely responsible for the cAMP production in spermatogenetic cells, we hypothesized that CFTR-mediated HCO3- transport was important to spermatogenesis via sAC pathway in spermatogenetic and Sertoli cells. Using intracellular pH measurement, we demonstrated that CFTR is involved in HCO3- transport in Sertoli cells. RT-PCR results showed that increased HCO3- concentrations in the culture medium resulted in upregulation of CFTR expression. The results also showed that the intracellular cAMP level in Sertoli cells increased as the extracellular HCO3- concentration increased. HCO3- also caused phosphorylation of the cAMP response element binding (pCREB) proteins transcription factor on serine 133, a modification known to be required by Sertoli cells to support spermatogenesis. This phosphorylation could be inhibited by CFTR inhibitor, further lending support to the notion that CFTR is important for HCO3- transport in Sertoli cells, leading to HCO3- dependent events that are important for spermatogenesis.
520 $a We further demonstrated the physiological role of CFTR in spermatogenesis using CFTR knockout mice as an in vivo model. Although TUNNEL staining showed normal percentage of apoptotic cells in seminiferous tubules, Cftr -/- mice had spermatogenetic defects in histology section and fewer number of mature sperm compared with wild type (WT) mice. Consistent with the proposed role of CFTR in spermatogenesis, RT-PCR and Western blot results showed reduced expression of spennatids specific gene, Protamine 1, Protamine 2, and CREM, which have been known to be involved in the process of spermatogenesis, in Cftr-/- mice.
520 $a Our study also detected CFTR in both human and mouse sperm. CFTR inhibitor or antibody significantly reduced sperm capacitation, and the associated HCO 3--dependent events including increases in intracellular pH, cAMP production and membrane hyperpolarization. The fertilizing capacity of the sperm obtained from heterozygous CFTR mutant mice is also significantly lower as compared to that of the wild type. These results suggest that CFTR in sperm may be involved in the transport of HCO3- important for sperm capacitation and that CFTR mutations with impaired CFTR function may lead to reduced sperm fertilizing capacity and male infertility other than CBAVD.
520 $a In conclusion, our study has demonstrated the role of CFTR in male reproductive system. We have further elucidated its possible physiological role and the underlying molecular mechanisms. These studies may pave the way for the development of method strategies for diagnosis and treatment of CFTR related infertility in male.
590 $a School code: 1307.
650 4 $a Biology, Animal Physiology. $3 1017835
690 $a 0433
710 2 $a The Chinese University of Hong Kong (Hong Kong). $3 1017547
773 0 $t Dissertation Abstracts International $g 69-08B.
790 $a 1307
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3326175