Deletions in L-type calcium channel alpha1 subunit testicular transcripts correlate with testicular cadmium and apoptosis in infertile men with varicoceles.
OBJECTIVE
To identify and understand predictors of successful varicocelectomy.


METHODS
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.


METHODS
University clinical urology practice and research laboratories.


METHODS
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).


METHODS
Left testis biopsies by percutaneous needle aspiration biopsy. Varicocele repair by subinguinal approach.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Benoff
Susan
S
Fertility Research Laboratories, North Shore-Long Island Jewish Research Institute, North Shore University Hospital, Manhasset, New York, USA.
Goodwin
Leslie O
LO
Millan
Colleen
C
Hurley
Ian R
IR
Pergolizzi
Robert G
RG
Marmar
Joel L
JL
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D001706:Biopsy; D002104:Cadmium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D013091:Spermatogenesis; D013737:Testis / Q000473:pathology / Q000502:physiology*; D014646:Varicocele / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D012333:RNA, Messenger; D002104:Cadmium