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L型钙通道α1亚基睾丸转录本的缺失与精索静脉曲张不育男性的睾丸镉含量及细胞凋亡相关。

Deletions in L-type calcium channel alpha1 subunit testicular transcripts correlate with testicular cadmium and apoptosis in infertile men with varicoceles.

作者信息

Benoff Susan, Goodwin Leslie O, Millan Colleen, Hurley Ian R, Pergolizzi Robert G, Marmar Joel L

机构信息

Fertility Research Laboratories, North Shore-Long Island Jewish Research Institute, North Shore University Hospital, Manhasset, New York, USA.

出版信息

Fertil Steril. 2005 Mar;83(3):622-34. doi: 10.1016/j.fertnstert.2004.07.976.

DOI:10.1016/j.fertnstert.2004.07.976
PMID:15749491
Abstract

OBJECTIVE

To identify and understand predictors of successful varicocelectomy.

DESIGN

Examination of testicular L-type voltage-dependent calcium channel (L-VDCC) mRNAs and proteins in testis biopsies and comparison of presence and absence of various mRNAs with testicular cadmium levels, with apoptosis, and with sperm count change after varicocelectomy.

SETTING

University clinical urology practice and research laboratories.

PATIENT(S): Infertile men with varicocele (left varicocele only, n = 18; bilateral varicoceles, n = 26) and controls (men with obstructive azoospermia undergoing testicular sperm extraction before intracytoplasmic sperm injection; n = 7).

INTERVENTION(S): Left testis biopsies by percutaneous needle aspiration biopsy. Varicocele repair by subinguinal approach.

MAIN OUTCOME MEASURE(S): Calcium channel mRNA sequence by reverse transcription-polymerase chain reaction and amplicon analysis; calcium channel protein distribution by immunocytochemistry; cadmium levels by atomic absorption and apoptosis by deoxynucleotidyl transferase labeling; and sperm counts in the ejaculate before and after varicocelectomy.

RESULT(S): Calcium channel mRNAs are polymorphic in human testis biopsies from different men. Proteins from sequence-deleted exons 7 and/or 8 localize to germ cell membranes. Expression of undeleted L-type calcium channel mRNAs correlates with normal testes cadmium and increased sperm count after varicocelectomy. Apoptosis is lower in such cases.

CONCLUSION(S): Expression of normal testicular L-VDCC sequence in exons 7-8 predicts postvaricocelectomy sperm count increase. Deletions may alter calcium channel function and affect testicular cadmium and apoptosis.

摘要

目的

识别并了解精索静脉曲张切除术成功的预测因素。

设计

检测睾丸活检组织中睾丸L型电压依赖性钙通道(L-VDCC)的mRNA和蛋白质,并比较各种mRNA的有无与睾丸镉水平、细胞凋亡以及精索静脉曲张切除术后精子计数变化之间的关系。

地点

大学临床泌尿外科实践与研究实验室。

患者

患有精索静脉曲张的不育男性(仅左侧精索静脉曲张,n = 18;双侧精索静脉曲张,n = 26)以及对照组(在卵胞浆内单精子注射前行睾丸精子提取术的梗阻性无精子症男性;n = 7)。

干预措施

经皮针吸活检获取左侧睾丸组织。采用腹股沟下途径进行精索静脉曲张修复术。

主要观察指标

通过逆转录-聚合酶链反应和扩增子分析检测钙通道mRNA序列;通过免疫细胞化学检测钙通道蛋白分布;通过原子吸收法检测镉水平,通过脱氧核苷酸末端转移酶标记法检测细胞凋亡;以及精索静脉曲张切除术前和术后射精中的精子计数。

结果

在来自不同男性的人类睾丸活检组织中,钙通道mRNA具有多态性。来自缺失序列的外显子7和/或8的蛋白质定位于生殖细胞膜。未缺失的L型钙通道mRNA的表达与正常睾丸镉水平以及精索静脉曲张切除术后精子计数增加相关。在这种情况下细胞凋亡较低。

结论

外显子7-8中正常睾丸L-VDCC序列的表达可预测精索静脉曲张切除术后精子计数增加。缺失可能会改变钙通道功能并影响睾丸镉水平和细胞凋亡。

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