Dysregulation of apoptotic pathway candidate genes and proteins in infertile azoospermia patients

Capsule:
An altered apoptotic pathway in impaired spermatogenic cases leads to infertility in males.

Authors:
Deepika Jaiswal, M.Sc., Sameer Trivedi, M.Ch., Neeraj K. Agrawal, D.M., Kiran Singh, Ph.D.

Volume 104, Issue 3, Pages 736-743

Abstract:

Objective:
To dissect the role of the apoptotic pathway and its regulation in the pathogenesis of male infertility in nonobstructive azoospermia.

Design:
Prospective study.

Setting:
University hospital.

Patient(s):
Sixty-three infertile azoospermic patients with different histologic phenotypes were recruited (obstructive azoospermia, n = 16; hypospermatogenesis, n = 11; maturation arrest, n = 15; Sertoli cell only, n = 21).

Intervention(s):
Testicular biopsies for histopathologic and expression analysis.

Main Outcome Measure(s):
Expression analysis by quantitative reverse transcription–polymerase chain reaction, protein localization by immunohistochemistry and apoptotic proteome array.

Result(s):
Results showed significantly increased expression of proapoptotic proteins like BAX, BAD, and BAK and comparatively lowered expression of antiapoptotic BCL2 and BCLW. Immunostaining revealed increased active caspase-3 activity and more TUNEL-positive cells in different impaired phenotypes as compared with normal. In addition, significantly increased m-RNA expression of TGFB1, P53, and FASLG along with significant down-regulation of VEGFA were observed. Expression of phosphorylated P53 at the S15 position and phosphorylated RAD17 at S635 was observed in cases with spermatogenic impairment at the translational level.

Conclusion(s):
The results clearly indicate increased levels of apoptosis along with its other regulatory factors. The balance between pro- (BAX and BAK) and antiapoptotic (BCL2 and BCLW) genes was disturbed, which may lead to altered apoptosis. Therefore, altered regulation of apoptosis might be associated with impaired spermatogenesis, eventually leading to male infertility.

  • msamplaski

    The authors conclude that in some infertile men,
    there is an imbalance between pro and antiapoptotic pathways. However, it is
    equally if not more likely that there is upregulation of proapoptotic pathways
    in men with hypospermatogenesis; ie that the cause of this upregulation is from
    the hypospermatogenic state. In addition, since these samples were obtained by percutaneous biopsy, it would be interesting to know if there was a degree of heterogeneity among samples within the same testis at MT.

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