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Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility

Methods

Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated.

Results

Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group.

Conclusion

AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

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Acknowledgments

We are thankful to Dr. Rashmi Bhilawadikar (Hinduja Hospital) for her help in collection of data for ICSI candidates. The help extended by staff of Hinduja Hospital IVF clinic and INKUS IVF centre is gratefully acknowledged. SS and PA are thankful to Indian Council of Medical Research (ICMR) for Senior Research Fellowship. SS is also thankful to Lady Tata Memorial Trust (LTMT) for Junior Research Fellowship. The work included in this publication (RA/219/01-2015) has been supported financially by grants from the Indian Council of Medical Research (ICMR), New Delhi, India to JG, DM and AP.

Conflict of interest

The authors have no competing interests to declare.

Authors’ contribution

S Sen: Sample collection, experimental standardization and work, data analysis and manuscript preparation

P Ambulkar: Sample collection, experimental standardization and work, data analysis and manuscript preparation

I Hinduja: Study design, recruitment of ICSI candidates and manuscript preparation

K Zaveri: Study design, recruitment of ICSI candidates and manuscript preparation

J Gokral: Initial conceptualization of the study, study design, patient recruitment and manuscript preparation

A Pal: Conceptualization of the project, data collection, data analysis, manuscript preparation and overall coordination

D Modi: Conceptualization of the project, data collection, data analysis, manuscript preparation and overall coordination

Author information

Authors and Affiliations

  1. Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India

    S. Sen & D. Modi

  2. Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India

    I. Hinduja & K. Zaveri

  3. Department of Reproductive Endocrinology and Infertility, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India

    J. Gokral

  4. Human Genetic Division, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, 442102, Wardha, India

    P. Ambulkar & A. Pal

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  1. S. Sen
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  3. I. Hinduja
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Correspondence to D. Modi.

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Capsule

AZFc subdeletions are a risk factor for male infertility in the Indian population. In men with AZFc subdeletions deletions of both DAZ and CDY1 copies increases the susceptibility to infertility. AZFc subdeletion screening would be clinically relevant for diagnosis of male infertility in Indian popualtion.

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Sen, S., Ambulkar, P., Hinduja, I. et al. Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions. J Assist Reprod Genet 32, 1333–1341 (2015). https://doi.org/10.1007/s10815-015-0520-4

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  • DOI: https://doi.org/10.1007/s10815-015-0520-4

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