Open Journal of Genetics, 2013, 3, 33-37 OJGen
http://dx.doi.org/10.4236/ojgen.2013.32A3005 Published Online August 2013 (http://www.scirp.org/journal/ojgen/)
Cytogenetic abnormalities in 200 male infertile cases in the
southern region of India*
G. Sreenivasa1, Suttur S. Malini1, Prasanna Kumari2, Usha R. Dutta3#
1Molecular Reproductive and Human Genetics Laboratory, Department of Studies in Zoology, University of Mysore, Mysore, India
2Department of Pathology (Cytog enetics), Kidwai Memorial Institute of Oncology, Bangalore, India
3Diagnostics Division, Center for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India
Received 21 June 2013; revised 2 July 2013; accepted 15 July 2013
Copyright © 2013 G. Sreenivasa et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Chromosomal abnormalities are one of the major
causes of male infertility. But the exact mechanism by
which chromosomal anomalies induces infertility is
still not clear. Many studies have documented the
chromosomal abnormalities ranging from 2.2% to
15.7% in infertile men. The present study has been
carried out to document and find out the genetic
cause of male infertility in the Southern region of In-
dia. The cytogenetic analysis of 200 male infertile
cases, referred due to primary infertility from 2009 to
2012, were analyzed by GTG banding and evaluated
retrospectively. The semen analysis was also per-
formed. A total of 15 cases (7.5%) showed chromo-
somal aberrations. Four (2%) were 47, XXY and mo-
saic 47,XXY; Two (1%) were structural autosomal
abnormalities; Two (1%) were inversion Y; Seven
(3.5%) cases were Y heterochromatin variants and
185 cases (92.5%) showed normal 46,XY karyotype.
The chromosomal abnormalities in our study is also
in agreement with the data from the literature. Also
abnormal spermatogenesis is observed in these cases.
Apart from chromosomal analysis further in depth
molecular analysis and genetic counseling is sugges-
tive in such cases, especially those interested in IVF
technologies.
Keywords: Male Infertility; Chromosomal
Abnormalities; Semen Analysis
1. INTRODUCTION
Male infertility is characterized by the in ability of a sex-
ually active, non-contraceptive couple to achieve preg-
nancy within one year [1]. It is a worldwide problem af-
fecting people of all communities, though the cause and
magnitude may vary with geographical location. The ex-
act cause of male infertility is still unknown in more than
50% of cases [2]. Due to the advancement in the diagno-
sis technologies in genetics, it is now becoming evident
that a significant percentage of male infertility cases are
due to genetic abnormalities [3]. Several studies have
shown increased chromosomal aberrations [4,5] in 5% to
7% of patients with oligospermia, and 10% to 15% in
patients with Azoospermia. Among several etiological
factors, chromosomal abnormalities play a significant
role in male infertility with 10% to 15% of aberrations
[6,7] among which 5% of these are numerical or struc-
tural abnormalities, 80% to 85% of cases are due to sex
chromosome anomalies and about 2% are mosaics with
autosomal abnormalities [8-11]. This value increases to
about 15% in Azoospermia males, largely due to cases
with 47,XXY aneuploidy. The most common type of
abnormality is Klinefelter Syndrome and also Y chromo-
some long arm micro deletion which is described as the
most frequent non chromosomal alteration [12]. Recent
studies demonstrated the association between rare ge-
netic sperm defects with a diverse inheritance pattern in
the family which may be transmissible to the male off-
spring [13]. In our study we aimed to investigate the per-
centage of chromosomal abnormalities associated among
infertile males in the southern region of India.
2. MATERIALS AND METHODS
The present study was conducted retrospectively from
2009 to 2012 in the Department of studies in Zoology of
our University. Blood samples of 200 infertile subjects
were collected from different IVF clinics and hospitals
referred due to primary and secondary infertility. Ethical
*Authors’ Disclosures of Potential Conflicts of Interest: No potential
conflicts of interest relevant to this article were reported.
#Corresponding author.

G. Sreenivasa et al. / Open Journal of Genetics 3 (2013) 33-37 34
clearance was obtained for this study from ethical com-
mittee of University of Mysore and concerned hospital.
Informed written consent was taken fro m all th e subj ects.
Genetic registry was established from the subjects, which
includes family history, reproductive history and life
style factors. All the patients underwent a detailed phy-
sical examination and semen analysis was performed ac-
cording to WHO guidelines [14]. Based on sperm count
the cases were classified into different groups. Azoo-
spermia is defined as the total absence of sperm cells and
oligozoospermia is the condition which occurs when the
sperm cell count is less than 5 × 106 cells/ml.
The Azoospermic group involved 48 cases, oligozoo-
spermic group involved 19 cases, associated oligozoo-
spermic groups like oligoasthenoteratozoosperic 17, oli-
goteratozoospermic 9, and oligoasthenozoospermic in-
volved 28 cases respectively, 40 cases were recorded as
teratozoospermia, 13 cases with asthenospermia, 9 cases
with asthenoteratozoospermia, 10 cases with ejaculation
failure and 7 cases with idiopathic condition.
Chromosomal analysis was performed on phytohe-
magglutinin (PHA) stimulated peripheral blood lympho-
cyte cultures using standard techniques [15]. GTG-band-
ing (G-banding using Trypsin and Giemsa) was per-
formed at approximately 400 - 450 band resolution [16].
About 50 metaphases were analyzed from each patient
and up to 100 metaphases in case of mosaicism. The
chromosomes were classified according to the Interna-
tional System for Human Cytogenetic Nomenclature
(ISCN) [17].
3. RESULT
A total of 200 cases with male infertility were evaluated
retrospectively. Fifteen out of the 200 (7.5%) cases
showed chromosomal aberrations. Four cases showed
numerical sex chromosomal abnormalities (2%). Out of
which two cases showed 47,XXY, third case showed
mosaic 47,XXY/46, XY and fourth case showed a mo-
saic karyotype of 47,XYY/46XY. Two cases showed
structural autosomal abnormalities (1%), the first case re-
vealed a karyotype of 46,XY,t(6;17)(p23;p13) and the
second case showed a deletion of 46,XY,del(9)(p11);
Two cases showed an inversion chromosome Y (1%),
one with a karyotype of 46,X,inv(Y)(p11.2q11.23) and
other showed 46,X,inv(Y)(p11.32q12). Seven cases showed
Y heterochromatin variations (3.5%) (Table 1).
Among azoospermic cases, 48 had normal karyotype
(24%) and 8 had ab normal karyotype (4%). In this stud y
Azoospermia condition scored 24%. Out of the 152 Oli-
gozoospermic cases 7 had abnormal karyotypes (3.5%).
Based on the sperm count we had subdivided them into
Teratozoospermia which scored 20%, Oligoasthenosper-
mia which scored 14%, other conditions like, Astheno-
spermia, Asthenoteratozoospermia, Oligoasthenoteratozoo-
spermia, Idiopathic, Oligoteratozoospermia, and Ejacula-
tion failure (Aspermia) scores less than 10%. Apparently,
in this study 14.5% of the Azoospermic cases, 15.7% of
Oligospermic, 11.75% of Asthenoteratozoospermia, 7.8%
of Asthenospermic, 5.8% of OAT, 5% of Teratozoosper-
mic and 3.5% of Oligoasthenospermic males were found
to be associated with chromosomal abnormalities (Fig-
ure 1).
The comparison of sperm parameters and the types of
chromosomal abnormality among infertile males varied
with the condition of the infertile subgroup. A total of 4
different numerical sex chro mosomal abnormalities were
observed, among them 2 cases are Klinefelter Syndrome,
one case with mosaic Klinefelter and one showed the
mosaic pattern of 46,XY/47,XYY were observed in the
Azoospermic condition. Two cases with structural ab-
normalities and a total of 9 cases showing ad dition, dele-
tion and inversion of Y chromosome in oligozoospermic
condition (Table 2).
4. DISCUSSION
Cytogenetic abnormalities have known to cause male in-
fertility, b ut the ex act mechanism by which chromosomal
anomalies induces infertility is still not clear. Chromo-
somal abnormalities include aberrations in the sex chro-
mosomes and autosomes like insertions or deletion of an
entire chromosome causing structural anomalies [18].
The sex chromosomes X and Y emerged from an auto-
some pair around 300 million years ago among the first
mammals [19]. The Y-chromosome has become special-
ized in the male sex determination, progressively de-
creasing its gene content by losing and gaining se-
quences through the action of events, such as, deletions,
mutations, insertions, recombination and transposition
[20]. Many studies have documented the chromosomal
A = Azoospermia, O = Oligospermia, OAT = Oligoasthenoteratozoospermia,
T = Teratozoospermia, OA = Oligoasthnospermia, AS = Asthenospermia,
OT = Oligoteratozoospermia, AT = Asthenoteratozoospermia, E = Ejacula-
tion failure, I = Idiopathic.
Figure 1. Distribution of infertile subgroups analyzed for chro-
mosomal abnormalities.

G. Sreenivasa et al. / Open Journal of Genetics 3 (2013) 33-37 35
Table 1. Distribution of different types of chromosomal abnormalities among infertile males.
Chromosomal abnormalities n = 200 %
Numerical sex chromosomal abnormality 4 2
47,XXY 2 1
47,mosXXY/46,XY 1 0.5
47,mosXYY/46,XY 1 0.5
Struct ural autosomal chromosomal abnormality 2 1
46,XY,t(6;17)(p23;p13) 1 0.5
46,XY,del(9)(p11) 1 0.5
Struct ural Y chromosome abnormality 09 4.5
46,XYq12h 4 2.0
46,XYq12h- 3 1.5
46,X,inv(Y)(p11.2q11.23) 1 0.5
46,X,inv(Y)(p11.32q12) 1 0.5
Normal 46,XY 185 92.5
Table 2. Cytogenetic abnormalities with respect to the sperm parameters in different infertile subgroups, IF = Infertile.
Karyotype (n = 15) IF Sperm count (millions/ml) Motility Morphology
47,XXY Azo 0 0% 0%
47,XXY Azo 0 0% 0%
mos47,XYY/46,XY Azo 0 0% 0%
mos47,XXY/46,XY Azo 0 0% 0%
46,XYq12h- Azo 0 0% 0%
46,XYq12h- OAT 10 5% 40%
46,XYq12h- Azo 2 15% 20%
46,XYq12h OA 5 0% 40%
46,XYq12h Azo 0 0% 0%
46,XYq12h T 0 0% 0%
46,XYq12h T 98 65% 15%
46,X,inv(Y)(p11.2q11.23) Azo 0 0% 0%
46,X,inv(Y)(p11.32q12) T 85 60% 15
46,XY,t(6;17)(p23;p13) AT 58 0% 10
46,XY,del(9)(p12) O 5 55% 21
abnormalities which ranges from 2.2% to 15.7% for in-
fertile men [18] in our study we observed that 7.5% of
the infertile males are associated with chromosomal ab-
normality.
Sex chromosome aberrations are the most frequently
observed conditions in male infertility. Klinefelter syn-
drome males can be identified only when they undergo
fertility assessments. VanAssche et al. [21] reported 11%
Azoospermic individuals with Klinefelter syndrome. In
our study among 48 (24%) of the Azoospermia cases,
4% cases were true Klinefelter syndrome, 2% with mo-
saic Klinefelter syndrome. The occurrence of Klinefelter
syndrome and XYY is due to meiotic non disjunction of
the X chromosome or anaphase lag of X chromosome
from a normal 46,XY or XXY zygote. This abnormality
is associated with severe spermatogenic failure causing a
marked reduction in testicular size and resulting in Azo-
ospermia [22]. Earlier studies have reported that the men
with XYY syndrome are generally fertile but appear to
have an increased likelihood of infertility compared to
karyotypically normal 46,XY males. This type of chro-
mosomal anomaly occurs in one for 1000 live male
births in the general population, but more frequent in the
infertile population (Martin , 2 008). We also h ad on e case
with a frequency of 0.5% associated with Azoospermic
condition having mosaic 46,XY/47,XYY karyotype. Few

G. Sreenivasa et al. / Open Journal of Genetics 3 (2013) 33-37 36
studies also reported the association of infertile patients
with 47,XYY syndrome [23]. Among Klinefelter and
47,XYY syndrome males, there is a theoretical risk re-
garding the m anifestat i on of sex chromosomal aneuploidy
in at least 50% of their sperms [24].
Recent study reported the higher incidence of chro-
mosomal abnormalities in azoospermic group than in the
oligospermic groups and also increased chromosomal
abnormalities with respect to decreased sperm count.
Some researchers who had investigated chromosomal
anomalies, specifically among patients with severe oli-
gospermia and Azoospermia, have reported higher fig-
ures such as 20.86% [11] and 21.1% [25] reported that
the incidence of chromosomal abnormalities was 14.3%
and 6.5% among Azoospermia and oligospermia respec-
tively, also Ceylan et al. [26] reported that, chromosomal
abnormality was 33.3% in the azoospermic and 13.3% in
severe oligozoospermic group. Chromosomal abnormali-
ties were detected in 17.4% of 86 azoospermic cases and
in 6.8% of 73 oligozoospermic cases in a regional study
in Turkey [27]. According to Samli et al. [28] chromo-
somal abnormality were associated with 12% of azoo-
spermic cases and in 4% of oligospermic patients. In our
study the incidence of the chromosomal abnormalities in
azoospermic and oligospermic males were found to be
14.5% and 5.2% respectively which accords with previ-
ous studies.
Additionally, the present study showed 2% of the as-
sociated oligospermic cases, like Oligo Asthenospermia
and oligoasthenoteratozoospermia condition showed Y
chromosomal heterochromatin variation with a frequency
of 1.2% have associated severe sperm defects. A rela-
tionship between balanced autosomal translocation and
infertility has been reported. In the present study one
case with (0.5%) 46,XY,t(6;17)(p23;p13) and one case
with deletion of 9p12 was observed. Many studies re-
ported that, the association of chromosome 9 in inver-
sion, translocation, and other chromosomal aberrations
with the male infertility which may result in various cli-
nical manifestations and also cause different kinds of
sperm abnormalities [27,29]. In the majority of cases,
carriers of balanced translocations are themselves pheno-
typically normal, unless one of the translocation break-
points interrupts an important gene or via position effect.
5. CONCLUSION
Chromosomal abnormalities play a significant role in
male infertility. In the present study it has been found
that the infertile males associated with chromosomal ab-
normalities involving structural as well as numerical al-
terations might have affected the spermatogenesis. How-
ever, further indepth Molecular analysis is needed to
understand the addition al genetical factors of male infer-
tility.
6. ACKNOWLEDGEMENTS
GS would like to thank UGC-RFSMS for the financial assistance.
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