Volume 6 Supplement 6

Beyond the Genome 2012

Open Access

A study on genetic aspects of male infertility in North-east Indian population, India

  • Purnali Nath Barbhuiya1,
  • Anannya Gogoi,
  • Giasuddin Ahmed3 and
  • Rita Mahanta4
BMC Proceedings20126(Suppl 6):P31

DOI: 10.1186/1753-6561-6-S6-P31

Published: 1 October 2012

Background

Male infertility refers to the inability of a male to achieve a pregnancy in a fertile female [1]. Genetic factors are an important cause of male infertility. The present study was aimed to determine the role of Y-chromosome microdeletion and mitochondrial DNA (mtDNA) mutations - two major causes of male infertility, with special emphasis on patients of North-east India.

Materials and methods

A total of 500 infertile male patients attending private infertility clinics of Guwahati, Assam, were selected for the study. Blood and semen samples were collected from the patients. Genomic DNA was isolated from both type of samples and PCR amplification was carried out using specific primer sets. The genes and sequence-tagged site (STS) markers included in the study are: DBY, USP9Y, PRY-2, RBMY, BPY-2, XKRY, CDY-1, CSPG4LY, DAZ, sY84, sY254, sY127, SY145, sY152 and sY153. All genes and STS were amplified efficiently in samples from 100 fertile men tested, but failed to be amplified in samples from fertile women. In order to study the role of mtDNA in sperm motility, semen DNA from 50 patients including 10 Asthenospermic, 20 Asthenoteratozoospermic and 20 oligoasthenoteratozoospermic patients and 20 fertile men were studied using specific primers for four mitochondrial genes, namely ND2, ND4, ATPase6 and ATPase8 followed by DNA sequencing.

Results

Among the 500 patients included in this study, 130 (26%) were azoospermic, 185 (37 %) were oligozoospermic and 185 (37 %) were asthenozoospermic. Analysis of PCR amplified products showed that the frequency of Yq microdeletion in semen samples was 20.8% (104/500) but 18.6% (93/500) in blood samples, both of which lies in the range ( 0%-55%) as stated by Kihaile et.al [2]. In blood samples frequency of Yq microdeletion was as followed: AZFa 4% (20/500), AZFb 5.6% (28/500), AZFc 5.8% (29/500) and AZFd 14.6% (73/500). Similarly, in semen samples frequency of Yq microdeletion was as followed: AZFa 6.4% (32/500), AZFb 6.6% (33/500), AZFc 7.6% (38/500) and AZFd 18.4% (92/500). For mtDNA mutation study the mutations that were present in both fertile and infertile samples, were A4769G (M100M) (Silent) in ND2, A8701G (T59A) (Novel) and A8860G (T112A) (Novel) in ATPase6 gene. The mtDNA mutations which were found only in infertile patient group were given in Table 1.
Table 1

mtDNA mutations found in infertile patients

Type of Infertility

Gene

At nucleotide position

At amino acid position

Nature of mutation

Asthenozoospermia

ND2

T4823C

V118V

Silent

Asthenozoospermia

ND2

T4993C

L175F

Novel

Asthenoteratozoospermia

ND2

C4730T

T87T

Silent

Asthenoteratozoospermia

ND2

T5250G

L261V

Novel

Asthenoteratozoospermia

ATPase8

G8557C

L64F

Novel

Oligoasthenoteratozoospermia

ATPase6

T8614G

L30V

Novel

Oligoasthenoteratozoospermia

ATPase6

A8925G

T133T

Silent

Oligoasthenoteratozoospermia

ATPase6

G9064A

A180T

Novel

Oligoasthenoteratozoospermia

ND4

A10978G

L73L

Silent

Conclusions

The study reveals that the frequency of Yq microdeletion is higher in semen samples than blood samples, possibly because most of the genes studied are testis-specific in nature. This is in accordance with the previous studies [3, 4]. In both types of samples AZFd regions has highest frequency of Yq microdeletion. The mtDNA mutations common in fertile and infertile patients have also been reported by other Indian researchers [5], but doubted to play any role in infertily [6]. The mutation G9064A in ATPase6 has also been reported to play a role in female infertility [7]. Beside these, the other mtDNA mutations observed in the present study have not been reported previously.

Declarations

Acknowledgements

This work was supported by DST Grant under the research project to Dr. Rita Mahanta and also DST grant under Women Scientist-A (WOS-A) scheme to PNBC. Authors are also thankful to the doctors and technicians of the infertility clinics from where the samples have been collected for their support.

Authors’ Affiliations

(1)
DBT-Sponsored Institutional Biotech Hubs, Cotton College
(2)
Department of Biotechnology, Gauhati University
(3)
Department of Zoology, Cotton College

References

  1. Nowier SR, El-sheikh MM, Abdel Rasool HA, Ismail S: Prevalence of Y chromosome microdeletion in males with azoospermia and severe oligospermia in Egypt. Res J Med Medical Sci. 2009, 4: 189-195.Google Scholar
  2. Kihaile PE, Yasui A, Shuto Y: Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin. J Exp Clin Assist Repro. 2005, 2: 9-10.1186/1743-1050-2-9.View ArticleGoogle Scholar
  3. Sakthivel JP, Swaminathan M: Y chromosome microdeletions in sperm DNA of infertile patients from Tamil Nadu, south India. Indian J Urol. 2008, 24: 480-485. 10.4103/0970-1591.44252.PubMed CentralView ArticlePubMedGoogle Scholar
  4. Dada R, Kumar R, Shamsi MB, et al: Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian J Androl. 2007, 9: 720-722. 10.1111/j.1745-7262.2007.00274.x.View ArticlePubMedGoogle Scholar
  5. Kumar R, Bhat A, Bamezai RN, et al: Necessity of nuclear and mitochondrial genome analysis prior to ART/ICSI. Indian J Biochem Biophys. 2007, 44: 437-42.PubMedGoogle Scholar
  6. Palanichamy MG, Zhang YP: Identifying potential pitfalls in interpreting mitochondrial DNA mutations of male infertility cases. Indian JMed Res. 2011, 134: 447-451.Google Scholar
  7. Venkatesh S, Kumar M, Sharma A, et al: Oxidative stress and ATPase6 mutation is associated with primary ovarian insufficiency. Arch Gynecol Obstet. 2010, 282: 313-318. 10.1007/s00404-010-1444-y.View ArticlePubMedGoogle Scholar

Copyright

© Barbhuiya et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement