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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Apoptosis / physiology*
  • Biopsy
  • Cadmium / metabolism*
  • Calcium Channels, L-Type / genetics*
  • Exons / genetics
  • Gene Deletion*
  • Humans
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Infertility, Male / physiopathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • Spermatogenesis
  • Testis / pathology
  • Testis / physiology*
  • Varicocele / metabolism
  • Varicocele / pathology
  • Varicocele / physiopathology*

Substances

  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • RNA, Messenger
  • Cadmium