Expression of SLC26A3, CFTR and NHE3 in the human male reproductive tract:: role in male subfertility caused by congenital chloride diarrhoea
Expression of SLC26A3, CFTR and NHE3 in the human male reproductive tract:: role in male subfertility caused by congenital chloride diarrhoea
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DOI：
10.1093/molehr/gal009
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Höglund, P
中科院分区：
文献类型：
--
作者：
Hihnala, S;Kujala, M;Höglund, P
先天性氯化物腹泻（CLD）是一种罕见的遗传性疾病，由溶质载体家族26成员3（SLC 26 A3）基因突变引起。肠内Cl-/HCO 3-交换的中断导致出生后的水样富Cl腹泻，最近观察到男性生育力低下是一种新的表现。采用免疫组织化学方法研究了SLC 26 A3及其相互作用蛋白囊性纤维化跨膜传导调节因子（CFTR）和Na+/H+交换器3（NHE 3）在CLD患者睾丸（n = 2）和输出小管（艾德）（n = 1）中的表达对照组睾丸、附睾（n = 11）、精囊（n = 9）和前列腺（n = 4）中的V317 del基因型表达阳性。SLC 26 A3免疫定位于伸长精子细胞（阶段III-VI）的头部，CFTR免疫定位于伸长精子细胞（阶段III和IV）和粗线期（阶段III-V）以及双线期精母细胞。在非纤毛细胞的艾德，顶端表达的所有三种蛋白质进行了观察，但只有SLC 26 A3和CFTR检测到的管腔边界上的顶端的富含细胞（AMRC）的附睾管和精囊上皮。只有CFTR存在于前列腺导管的上皮细胞。在CLD患者中，SLC 26 A3和CFTR在艾德中均不表达，但睾丸表达与对照组相同。这些结果表明SLC 26 A3在雄性生殖中的主要作用。CFTR和NHE 3的组织特异性共表达支持SLC 26 A3的多种功能，并可能对CLD和囊性纤维化（CF）以及精子囊肿中的男性生育力低下的病理生理学产生影响。
Congenital chloride diarrhoea (CLD) is a rare inherited disease caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene. Disruption of intestinal Cl-/HCO3- exchange causes watery Cl- rich diarrhoea from birth, and recently male subfertility was observed as a novel manifestation. Expression of SLC26A3, together with interacting proteins cystic fibrosis transmembrane conductance regulator (CFTR) and Na+/H+ exchanger 3 (NHE3), was studied using immunohistochemistry in the testis (n = 2) and efferent ducts (ED) (n = 1) of patients with CLD (V317del genotype) and in the testis and epididymis (n = 11), seminal vesicle (n = 9) and prostate (n = 4) of the controls. SLC26A3 was immunolocalized in the head of the elongating spermatids (stages III-VI) and CFTR in the elongating spermatids (stages III and IV) and pachytene (stages III-V) and diplotene spermatocytes. In the non-ciliated cells of the ED, apical expression of all three proteins was observed, but only SLC26A3 and CFTR were detected on the luminal border of the apical mitochondria-rich cells (AMRC) of the ductus epididymis and in the epithelium of the seminal vesicle. Only CFTR was present in the epithelium of the prostatic duct. In the patient with CLD, the expression of both SLC26A3 and CFTR was absent in the ED, but testicular expression was identical to that of the controls. These results suggest a primary role for SLC26A3 in male reproduction. Tissue-specific co-expression with CFTR and NHE3 supports diverse functions of SLC26A3 and may have an impact on pathophysiology of male subfertility both in CLD and in cystic fibrosis (CF), as well as spermatoceles.