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. 2019 Nov 10;14:854–862. doi: 10.1515/med-2019-0100

Clinical Features of Infertile Men Carrying a Chromosome 9 Translocation

Ruixue Wang 1, Yang Yu 1, Qiyuan Wang 2, Yuting Jiang 1, Linlin Li 1, Haibo Zhu 1, Ruizhi Liu 1, Hongguo Zhang 1,*
PMCID: PMC6843491  PMID: 31737790

Abstract

Previous studies indicated that chromosome 9 translocations are involved in reduced male fertility and increased chance of miscarriage in the female partner. The aim of this study was to review the clinical features and genetic counselling requirements of infertile men carrying chromosome 9 translocations. This study analyzed fertile-age male carriers of chromosome 9 translocations, and included 12 clinical cases in our hospital. In our cases, three cases had oligozoospermia or severe oligozoospermia, while nine cases had normal semen. Of the latter nine cases, seven were associated with recurrent spontaneous abortions, and two produced a phenotypically normal child as confirmed by amniocentesis. Male chromosome 9 translocations and specific breakpoints from reported papers were searched using PubMed and CNKI database. A literature review identified 76 male patients who carried chromosome 9 translocations. Breakpoints at 9p12, 9p11, 9p10 and 9q34.1 were related to pregestational infertility, while breakpoints at 9p21, 9q10, 9q11, 9q13, 9q21.1, 9q22, 9q22.2, 9q22.3, 9q34, 9q34.2 and 9q34.3 exhibited gestational infertility. Chromosome translocations involving chromosome 9 lead to increased risk of miscarriage. Carriers of chromosome 9 translocations should be counselled to consider in vitro fertilization accompanied by preimplantation genetic diagnosis.

Keywords: Male infertility, Chromosomal translocation, Chromosome 9, Breakpoint, Genetic counselling

1. Introduction

Balanced reciprocal translocations are structural chromosomal abnormalities. Male carriers may have high rates of genetically unbalanced spermatozoa and exhibit impaired spermatogenesis, associated with frequent unbalanced embryos, male infertility or increased miscarriages [1, 2, 3]. However, clinical cases of normal male fertility with no history of related abortion can also be found for individuals with balanced translocations. Additionally, although in vitro fertilization accompanied by preimplantation genetic diagnosis (PGD) increased the chance of translocation carriers fathering a healthy child [4], some studies suggested that PGD did not make better for live birth rate and repeated miscarriage of couples with balanced translocations [5,6]. Natural conception is still a possible option for these carriers’ couples [7,8]. Hence, genetic counselling remains a challenge for carriers of balanced translocations.

Recently, we reported and reviewed the relationship between translocation breakpoints of chromosomes 2, 3, 5, and 6, and infertility for male carriers [9, 10, 11, 12, 13]. Previous studies indicated that chromosome 9 translocations are involved in reduced male fertility and increased chance of miscarriage in the female partner [4,14,15]. The chromosomes and specific breakpoints involved in the translocation are closely related to reproductive abnormalities [16,17]. Chromosomal translocation can increase the frequency of spermatozoa carrying an abnormal chromosome constitution, and some translocation breakpoints can disrupt important genes involved in spermatogenesis [10]. Testis-specific protein kinase 1 gene (TESK1) is located on chromosome 9p13.3 and is specifically expressed in testicular germ cells [18]. Thioredoxin domain-containing protein 8 gene (TXNDC8), mapped to chromosome 9q31.3, may be associated with late sperm maturation [19]. Additionally, chromosome 9 was the first chromosome found to be frequently associated with infertile patients [20]. Understanding the breakpoints on chromosome 9 with respect to providing genetic counselling for male infertility warrants further research.

The aim of this study is to identify potential correlations between clinical characteristics of male infertility and carriers of specific translocation breakpoints in chromosome 9.

2. Methods

Twelve male carriers of chromosome 9 translocations experiencing infertility or receiving counselling were recruited from the outpatient’s department at the Center for Reproductive Medicine, First Hospital of Jilin University, Changchun, China between July 2010 and December 2017. This study included all translocation cases involving chromosome 9, and excluded the patients with varicocele, ejaculatory duct obstruction and the other cause of infertility. Each patient underwent semen and cytogenetic analysis. Abortions due to the female factor were excluded. This study was approved by the Ethics Committee of the First Hospital of Jilin University, and written informed consent was provided by each patient.

For each patient, a semen sample obtained by masturbation after 3-7 days of abstinence was allowed to liquefy at room temperature, and was then analyzed using standard techniques recommended by the World Health Organization guidelines. Patients with oligozoospermia were diagnosed with a sperm count less than 15×106/ml in their last three semen samples (taken at intervals of 1–3 weeks). Oligozoospermia and severe oligozoospermia were defined as previously described [2]. Chromosome preparations were obtained from lymphocyte cultures derived from each patient. Karyotype analysis after G-banding of metaphase chromosomes followed our previously reported methods [11].

Male chromosome 9 translocations and specific breakpoints from reported papers were searched using PubMed, Google Scholar and CNKI database. The search keywords were “chromosome/ translocation/sperm” and “chromosome/translocation/ abortion”. This study included male cases of adult fertile-age, and excluded females and newborns carriers, those with complex chromosomal translocations, chimeras or bone marrow detection, and other cases without breakpoints involving chromosome 9 in the reported papers.

3. Results

This study clinically examined a total of 12 men with chromosome 9 translocations. Karyotype results and G-banding karyotypes from these 12 patients are shown in Table 1 and Figure 1, respectively. Three cases had oligozoospermia or severe oligozoospermia (pregestational infertility), while nine cases had normal semen. Of the former three cases, the carrier with t(1; 9) (p32; p24) showed oligozoospermia, and the other two carriers manifested severe oligozoospermia. After genetic counselling and informed consent, the use of intracytoplasmic sperm injection combined with PGD should be carefully considered for these patients. Of the latter nine cases, it was evident that the carriers’ wife had a tendency to miscarry (gestational infertility); two cases with t(3;9)(q21;q22) and t(8;9)(q24;q32) produced a phenotypically normal child as confirmed by amniocentesis, respectively, and the other seven cases had experienced recurrent miscarriage. For these patients, PGD or prenatal diagnosis should be considered to improve pregnancy rates and reduce abortion rates.

Table 1.

Karyotypes of chromosome 9 translocation carriers and their clinical features

Infertility type Clinical findings Karyotype Figure No.
Pregestational Oligozoospermia or severe oligozo- ospermia 46,XY,t(1;9)(p22;p24) Figure 1a
46,XY,t(1;9)(p32;p24) Figure 1b
46,XY,t(9;15)(p13;q11) Figure 1c
Gestational Normal sperm density; a history of miscarriage or Natural pregnancy 46,XY,t(1;9)(p36;q32) Figure 1d
46,XY,t(3;9)(q21;q22) Figure 1e
46,XY,t(4;9)(q35;p13) Figure 1f
46,XY,t(6;9)(q26;p13) Figure 1g
46,XY,t(8;9)(q24;q32) Figure 1h
46,XY,t(5;9)(p13;q22) Figure 1i
46,XY,t(7;9)(p10;q10) Figure 1j
46,XY,t(9;15)(p24;q22) Figure 1k
46,XY,t(9;10)(q21;q22) Figure 1l
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Figure 1.

Figure 1

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G-banding karyotypes of the 12 cases identified as possessing chromosome 9 translocations. a: t(1;9) (p22;p24); b: t(1;9) (p32;p24); c: t(9;15) (p13;q11); d: t(1;9); e: t(3;9); f: t(4;9); g: t(6;9); h: t(8;9); i: t(5;9); j: t(7;9); k: t(9;15) (p24;q22); l: t(9;10).

From a review of the literature, clinical feature, karyotype, and specific breakpoints on chromosome 9 were collected and are summarized in Table 2. The reported paper included 76 carriers of chromosome 9 translocations. Combined with the 12 cases reported in this study, chromosome 1 (11 cases) is the most frequently involved with chromosome 9 translocation. In cases of male infertility, the distribution of other chromosomes involved in the translocation with chromosome 9 is shown in Figure 2. The distribution suggests that balanced translocation is closely related to male fertility, and multiple breakpoints on chromosome 1 are involved in these translocations. However, chromosome 11 was not found to be involved in translocation with chromosome 9.

Table 2.

Breakpoints in chromosome 9 translocation carriers and clinical features reported in previous literature

Cases Karyotype Breakpoints Clinical findings Reference
1 t(1;9) 1q11;9p24 severe oligozoospermia Yoshida et al., 1997 [75]
2 t(1;9) 1q43; 9p23 Oligoasthenozoospermia Perrin et al., 2013 [45]
3 t(1;9) 1q11; 9p13 Azoospermia or severe oligozoospermia Mierla et al., 2014 [14]
4 t(1;9) 1q12; 9q13 PGD Zhang et al., 2014 [81]
5 t(1;9) 1q23; 9q22.3 Recurrent miscarriage Dutta et al., 2011 [38]
6 t(1;9) 1q42.3; 9q22.3 Recurrent miscarriage Sugiura-Ogasawara., 2008[56]
7 t(1;9) 1q22; 9q31 Infertility Martin, 1992 [61]
8 t(1;9) 1p32.1; 9q34.3 Normal sperm count Matsuda et al., 1992 [36]
9 t(2;9) 2q21; 9p22 Infertility Martin et al., 1990 [60]
10 t(2;9) 2q32; 9q31 ICSI Gekas et al., 2001 [52]
11 t(2;9) 2q33; 9q34 PGD Findikli et al., 2003 [51]
12 t(2;9) 2q37; 9q22 2 fetal losses Adamoli et al., 1986 [42]
13 t(2;9) 2q37.3; 9q12 Normal semen Dul et al., 2012 [54]
14 t(3;9) 3p25; 9q32 Infertility Honda et al., 1999 [64]
15 t(3;9) 3q21; 9q34 PGD Findikli et al., 2003 [51]
16 t(3;9) 3q26.2; 9q32 Infertility Honda et al., 1999 [64]
17 t(3;9) 3q28; 9q32 Azoospermia or severe oligozoospermia Mierla et al., 2014 [14]
18 t(4;9) 4p15.2; 9p13 Recurrent spontaneous abortions Celep et al., 2006 [78]
19 t(4;9) 4q23.2; 9q22.3 Recurrent pregnancy loss Kochhar et al., 2013 [15]
20 t(4;9) 4q25; 9p22 Infertility Moretti et al., 2009 [73]
21 t(4;9) 4q31.1; 9p24 Recurrent spontaneous abortions Celep et al., 2006 [78]
22 t(5;9) 5p15.1; 9q22.1 Primary infertility Vozdova et al., 2013 [4]
23 t(5;9) 5p13; 9q22 PGD Zhang et al., 2014 [81]
24 t(5;9) 5p12; 9p11 Infertility Pellestor et al., 2001 [66]
25 t(5;9) 5q10; 9q10 Infertility Rouen et al., 2017 [35]
26 t(5;9) 5q23.2; 9q22.3 Spontaneous abortion Stephenson et al., 2006 [48]
27 t(5;9) 5q23.3; 9p24 Repeated miscarriages Iyer et al., 2007 [55]
28 t(6;9) 6p12; 9q13 PGD, No pregnancy Escudero et al., 2003 [76]
29 t(7;9) 7p15.2; 9q34.1 Primary infertility Vozdova et al., 2013 [4]
30 t(7;9) 7p14.2; 9q32 Recurrent miscarriage Pundir et al., 2016 [57]
31 t(7;9) 7p13; 9p23 ICSI Gekas et al., 2001 [52]
32 t(7;9) 7p13; 9q21 Teratozoospermia Rouen et al., 2013[39]
33 t(7;9) 7q31; 9q34 Early miscarriage Olszewska et al., 2017 [43]
34 t(7;9) 7q33; 9p21 Infertility Pellestor et al., 1997 [63]
35 t(7;9) 7q36.2; 9p21.2 Normal semen Wiland et al., 2008 [74]
36 t(8;9) 8p21; 9p24 Spontaneous abortions Bourrouillou et al., 1986 [47]
37 t(8;9) 8p21; 9q34 Early miscarriage Olszewska et al., 2017 [43]
38 t(8;9) 8q24.2; 9q32 Infertility Estop et al., 1998 [68]
39 t(8;9) 8q24.3; 9p21.2 Severe oligozoospermia; Olszewska et al., 2017 [43]
40 t(8;9) 8q24.2; 9q32 Infertility Estop et al., 2000 [65]
41 t(8;9) 8q24.3; 9p24 Infertility Ferfouri et al., 2013 [71]
42 t(9;10) 9q11; 10p11.1 Repetitive abortions Rives et al., 2003 [67]
43 t(9;10) 9q12; 10q26 Azoospermia or severe oligozoospermia Mierla et al., 2014 [14]
44 t(9;10) 9q34; 10q11 Infertility Martin, 1988 [59]
45 t(9;10) 9q34.3; 10q24.1 PGD Ko et al., 2010 [40]
46 t(9;12) 9p22; 12q22 Recurrent fetal wastage Fryns et al., 1998 [79]
47 t(9;13) 9p23; 13q21.1 PGD Ko et al., 2010 [40]
48 t(9;13) 9q21.1; 13q21.2 Infertility Martin et al., 1995 [62]
49 t(9;13) 9q31; 13q34 Recurrent pregnancy loss Kochhar et al., 2013 [15]
50 t(9;13) 9q32; 13q32 Recurrent miscarriage Sugiura-Ogasawara., 2008 [56]
51 t(9;14) 9p13; 14q13 Normal semen Wiland et al., 2008 [74]
52 t(9;14) 9q22.1; 14q12 Infertility Gada Saxena et al., 2012 [80]
53 t(9;14) 9q32; 14p11.2 Severe oligozoospermia Brugnon et al., 2006 [49]
54 t(9;15) 9p10; 15q10 Oligoasthenoteratozoospermia Aydos et al., 2006 [72]
55 t(9;15) 9q32; 15q24 Multiple Abortions Castle et al., 1988 [41]
56 t(9;16) 9q34.2; 16p12 Normal semen Douet-Guilbert et al.,2005 [50]
57 t(9;17) 9p13; 17q21.3 Normal sperm count Perrin et al., 2009 [77]
58 t(9;17) 9p13; 17q21.3 Infertility Benet et al., 2005 [70]
59 t(9;17) 9p12; 17q24 Oligozoospermia Antonelli et al., 2000 [46]
60 t(9;17) 9q12; 17p12 Infertility Benet et al., 2005 [70]
61 t(9;17) 9q21; 17p11.2 PGD, Delivery Kyu Lim et al., 2004 [37]
62 t(9;17) 9q22; 17p13 Normal semen Brugnon et al., 2006 [49]
63 t(9;17) 9q22.1; 17p13.1 Repeated spontaneous abortions Ghazaey et al., 2015 [3]
64 t(9;18) 9p12; 18q12.1 Infertility Pellestor et al., 1989 [44]
65 t(9;18) 9q22.2; 18p11.31 Recurrent miscarriage Pundir et al., 2016 [57]
66 t(9;18) 9q32; 18q23 Recurrent miscarriage Pundir et al., 2016 [57]
67 t(9;19) 9q10; 19p10 Increased aneuploid sperm Godo et al., 2013 [17]
68 t(9;19) 9q10; 19p10 Not recorded Anton et al., 2008 [53]
69 t(9;20) 9p24; 20q13.1 Oligozoospermia and astenozoospermia Anton et al., 2008 [53]
70 t(9;20) 9q13.4;20p11.2 Normal sperm count Yoshida et al., 1997 [75]
71 t(9;21) 9p21; 21q22 Recurrent abortion Gaboon et al., 2015 [58]
72 t(9;21) 9p13; 21q22.1 PGD Zhang et al., 2014 [81]
73 t(9;21) 9q11; 21q10 IVF Findikli et al., 2003 [51]
74 t(9;22) 9q21; 22q11.2 Oligospermia and asthenospermia Perrin et al., 2009 [77]
75 t(9;22) 9q21; 22q11.2 Oligozoospermia Douet-Guilbert et al.,2005 [50]
76 t(9;22) 9q21; 22q11.2 Infertility Morel et al., 2004 [69]
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Figure 2.

Figure 2

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Distribution of chromosomes involved in translocations with chromosome 9.

The breakpoints at 9q32, 9p24 and 9p13 were observed in 12 cases (13.6%), 10 cases (11.4%) and 9 cases (10.2%) respectively. The breakpoints at 9p12, 9p11, 9p10 and 9q34.1 were related to pregestational infertility, while breakpoints at 9p21, 9q10, 9q11, 9q13, 9q21.1, 9q22, 9q22.2, 9q22.3, 9q34, 9q34.2 and 9q34.3 exhibited gestational infertility. Other breakpoints were found with cases of either pregestational or gestational infertility (Table 3).

Table 3.

Incidence of breakpoints on chromosome 9

Breakpoints Number of patients with pre-gestational infertility Number of p atients with gestational infertility Total (%)
p24 5 5 10(11.4%)
p23 2 1 3(3.4%)
p22 2 1 3(3.4%)
p21.2 1 1 2(2.3%)
p21 2 2(2.3%)
p13 2 7 9(10.2%)
p12 2 2(2.3%)
p11 1 1(1.1%)
p10 1 1(1.1%)
q10 3 3(3.4%)
q11 2 2(2.3%)
q12 1 2 3(3.4%)
q13 2 2(2.3%)
q13.4 1 1(1.1%)
q21 4 2 6(6.8%)
q21.1 1 1(1.1%)
q22 5 5(5.7%)
q22.1 1 2 3(3.4%)
q22.2 1 1(1.1%)
q22.3 4 4(4.5%)
q31 2 1 3(3.4%)
q32 3 9 12(13.6%)
q34 5 5 (5.7 %)
q34.1 1 1 (1.1 %)
q34.2 1 1 (1.1 %)
q34.3 2 2 (2.3%)
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4. Discussion

This study reports the karyotype and clinical manifestations of 12 cases with chromosome 9 translocations. Three cases had oligozoospermia or severe oligozoospermia, seven cases were associated with recurrent spontaneous abortions, and two cases each produced a phenotypically normal child (confirmed by amniocentesis). Pregestational and gestational infertility are the most typical two types for infertile male [21]. This study included three cases that exhibited pregestational infertility, and seven cases that exhibited gestational infertility. These patients may consider intracytoplasmic sperm injection or PGD combined within vitro fertilization to reduce subsequent miscarriage rate. The two cases that produced a phenotypically normal child indicated that carriers have a chance of natural conception. The live birth rate in patients with chromosomal translocations choosing to conceive naturally was reported to be 37–63% for the first pregnancy, and then a cumulative rate of 65–83% [22].

To study the role of breakpoints on chromosome 9 in male infertility, the previously published literatures were reviewed. The clinical findings and karyotype regarding chromosome 9 are shown in Table 2. For all carriers from our study and reported literature, the most common chromosome and breakpoint involved chromosome 9 translocation were t(1;9) (12.5%) and 9q32 (13.6%) respectively. Chromosome 1 was most involved with chromosome 9 translocation in this study. For translocation carriers involved in chromosome 1, the clinical phenotype is more likely to be related to chromosome 1. Previous literatures have reported that there are more genes related to spermatogenesis on chromosome 1 [23,24]. The breakpoints on chromosome 1 could interfere with spermatogenesis, leading to azoospermia. In genetic counselling, the breakpoints on chromosome 1 should be considered for the translocation carriers involved in t (1; 9).

Breakpoints at 9p12, 9p11, 9p10 and 9q34.1 were found with pregestational infertility, while breakpoints at 9p21, 9q10, 9q11, 9q13, 9q21.1, 9q22, 9q22.2, 9q22.3, 9q34, 9q34.2 and 9q34.3 exhibited gestational infertility. Therefore, more chromosome 9 breakpoints exhibited gestational (compared with pregestational) infertility, in which the carriers’ wife had a tendency to miscarry. Other breakpoints were found with cases of pregestational or gestational infertility. Previous studies have shown that certain genes on chromosome 9 are involved in spermatogenesis. For example, the aquaporin 7 gene (AQP7), located on chromosome 9p13.3, is expressed during the late stages of spermatogenesis [25]. Spermatogenic failure 8 gene (SPGF8), mapped to chromosome 9q33.3, is associated with severe spermatogenic failure [26]. The outer dense fiber of sperm tails 2 gene (ODF2), mapped to chromosome 9q34.11, has a key role in the formation of sperm flagella [27]. Doublesex-and mab3-related transcription factor 1 (DMRT1) and DMRT3, mapped to chromosome 9p24.3, are expressed in germ cell and Sertoli cells [28]. Relaxin 1 (RLN 1) and RLN2, mapped to chromosome 9p24.1, are highly expressed in the prostate and testis [29]. Lysine-specific demethylase 4c (KDM4C) located on chromosome 9p24.1 regulates histone modifications and androgen receptor function [30]. Testis expressed 48 (TEX 48) and TEX53, mapped to chromosome 9q32, are testis-specific genes [31]. The specific function of these genes needs further investigation. Kim et al [32] reported that breakpoints at 9p22; 9p11.2, 9q21.2 and 9q22 were found with cases of impaired spermatogenesis, and breakpoints at 9p23.24, 9p23, 9p12 and 9q22 were associated with recurrent abortion. The key difference between the above paper and our current study is that their subjects had complex chromosomal rearrangements. The carrier is more likely to have normal sperm in semen when they involve balanced translocation of two chromosomes. For the carriers of complex chromosomal rearrangements, the probability of abnormal spermatogenesis increase greatly.

Male carriers of chromosome translocations are phenotypically normal, but may produce genetically unbalanced spermatozoa, leading to unbalanced embryos and miscarriage. Translocations may alter the process of spermatogenesis, resulting in azoospermia or oligospermia [33]. To explain the associated clinical pregestational or gestational infertility, three hypotheses have been proposed, including a break within a gene, a positional effect, and cryptic deletion or duplication [34]. During genetic counselling, physicians should consider the breakpoints involved in the translocation. When receiving genetic counselling, the carriers of chromosome 9 translocations should consider suitable reproductive options, including continued attempts at natural conception or in vitro fertilization accompanied by PGD.

Limitations of this study include the small number of carriers of chromosome 9 translocations, and the lack of detailed research regarding the specific molecular effects of each translocation by molecular-cytogenetic methods. According to our knowledge, this study is the first review of male carriers involved in chromosome 9 translocation published in previous literature, which will provide reference for clinical genetic counselling.

5. Conclusion

In the present study, the most common breakpoints involving chromosome 9 translocation were t(1;9) and 9q32 respectively. Most breakpoints at chromosome 9 exhibited gestational infertility. Carriers of chromosome 9 translocations should be counselled to consider in vitro fertilization accompanied by PGD.

Acknowledgment

We thank Charles Allan, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

Footnotes

Funding This work was supported by the Special Funds of Jilin Province Development and Reform Commission, China (2017C025).

Conflict of interest The authors have declared no conflicts of interest.

References

  • [1].Fiorentino F, Spizzichino L, Bono S. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26:1925–1935. doi: 10.1093/humrep/der082. et al. [DOI] [PubMed] [Google Scholar]
  • [2].Zhang HG, Wang RX, Li LL. Male carriers of balanced reciprocal translocations in Northeast China: sperm count, reproductive performance, and genetic counseling. Genet Mol Res. 2015;14:18792–18798. doi: 10.4238/2015.December.28.28. et al. [DOI] [PubMed] [Google Scholar]
  • [3].Ghazaey S, Keify F, Mirzaei F, Maleki M. Chromosomal analysis of couples with repeated spontaneous abortions in northeastern iran. Int J Fertil Steril. 2015;9:47–54. doi: 10.22074/ijfs.2015.4208. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Vozdova M, Oracova E, Kasikova K. Balanced chromosomal translocations in men: relationships among semen parameters, chromatin integrity, sperm meiotic segregation and aneuploidy. J Assist Reprod Genet. 2013;30:391–405. doi: 10.1007/s10815-012-9921-9. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].De Krom G, Arens YH, Coonen E. Recurrent miscarriage in translocation carriers: no differences in clinical characteristics between couples who accept and couples who decline PGD. Hum Reprod. 2015;30:484–489. doi: 10.1093/humrep/deu314. et al. [DOI] [PubMed] [Google Scholar]
  • [6].Franssen MT, Musters AM, van der Veen F. Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review. Hum Reprod Update. 2011;17:467–475. doi: 10.1093/humupd/dmr011. et al. [DOI] [PubMed] [Google Scholar]
  • [7].Scriven PN, Flinter FA, Khalaf Y. Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study. Eur J Hum Genet. 2013;21:1035–1041. doi: 10.1038/ejhg.2013.9. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Flynn H, Yan J, Saravelos SH. Comparison of reproductive outcome, including the pattern of loss, between couples with chromosomal abnormalities and those with unexplained repeated miscarriages. J Obstet Gynaecol Res. 2014;40:109–116. doi: 10.1111/jog.12133. et al. [DOI] [PubMed] [Google Scholar]
  • [9].Zhang X, Zhang H, Hu C. Clinical features of carriers of reciprocal chromosomal translocations involving chromosome 2: report of nine cases and review of the literature. Int Braz J Urol. 2018;44:785–793. doi: 10.1590/S1677-5538.IBJU.2017.0233. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Zhang H, Wang R, Li L. Translocation breakpoints of chromosome 3 in male carriers: a report of twelve cases and a review of the literature. Turk J Med Sci. 2018;48:150–156. doi: 10.3906/sag-1704-1. et al. [DOI] [PubMed] [Google Scholar]
  • [11].Zhang HG, Wang RX, Pan Y. A report of nine cases and review of the literature of infertile men carrying balanced translocations involvingchromosome 5. Mol Cytogenet. 2018;11:10. doi: 10.1186/s13039-018-0360-x. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Yang X, Zhang H, Yu Y. Clinical Features of Chromosome 6 Translocation in Male Carriers: A Report of 10 Cases and Review of the Literature. Med Sci Monit. 2018;24:4162–4168. doi: 10.12659/MSM.911170. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Zhang H, Wang R, Li L. Clinical feature of infertile men carrying balanced translocations involving chromosome 10: Case series and a review of the literature. Medicine (Baltimore) 2018;97:e0452. doi: 10.1097/MD.0000000000010452. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Mierla D, Jardan D, Stoian V. Chromosomal abnormality in men with impaired spermatogenesis. Int J Fertil Steril. 2014;8:35–42. [PMC free article] [PubMed] [Google Scholar]
  • [15].Kochhar PK, Ghosh P. Reproductive outcome of couples with recurrent miscarriage and balanced chromosomal abnormalities. J Obstet Gynaecol Res. 2013;39:113–120. doi: 10.1111/j.1447-0756.2012.01905.x. [DOI] [PubMed] [Google Scholar]
  • [16].Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14:32–39. doi: 10.1038/aja.2011.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Godo A, Blanco J, Vidal F. Accumulation of numerical and structural chromosome imbalances in spermatozoa from reciprocal translocation carriers. Hum Reprod. 2013;28:840–849. doi: 10.1093/humrep/des431. et al. [DOI] [PubMed] [Google Scholar]
  • [18].Toshima J, Ohashi K, Okano I. Identification and characterization of a novel protein kinase, TESK1, specifically expressed in testicular germ cells. J Biol Chem. 1995;270:31331–31337. doi: 10.1074/jbc.270.52.31331. et al. [DOI] [PubMed] [Google Scholar]
  • [19].Jiménez A, Zu W, Rawe VY. Spermatocyte/spermatid-specific thioredoxin-3, a novel Golgi apparatus-associated thioredoxin, is a specific marker of aberrant spermatogenesis. J Biol Chem. 2004;279:34971–34982. doi: 10.1074/jbc.M404192200. et al. [DOI] [PubMed] [Google Scholar]
  • [20].Manvelyan M, Schreyer I, Höls-Herpertz I. Forty-eight new cases with infertility due to balanced chromosomal rearrangements: detailed molecular cytogenetic analysis of the 90 involved breakpoints. Int J Mol Med. 2007;19:855–864. doi: 10.3892/ijmm.19.6.855. et al. [DOI] [PubMed] [Google Scholar]
  • [21].Li D, Zhang H, Wang R. Chromosomal abnormalities in men with pregestational and gestational infertility in northeast China. J Assist Reprod Genet. 2012;29:829–836. doi: 10.1007/s10815-012-9783-1. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Ikuma S, Sato T, Sugiura-Ogasawara M. Preimplantation genetic diagnosis and natural conception: a comparison of live birth rates in patients with recurrent pregnancy loss associated with translocation. PLos One. 2015;10:e0129958. doi: 10.1371/journal.pone.0129958. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Bache I, Assche EV, Cingoz S. An excess of chromosome 1 breakpoints in male infertility. Eur J Hum Genet. 2004;12:993–1000. doi: 10.1038/sj.ejhg.5201263. et al. [DOI] [PubMed] [Google Scholar]
  • [24].Wang RX, Zhang HG, Pan Y. Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling. Genet Mol Res. 2016;15 doi: 10.4238/gmr.15048707. et al. gmr.15048707. [DOI] [PubMed] [Google Scholar]
  • [25].Ishibashi K, Yamauchi K, Kageyama Y. Molecular characterization of human Aquaporin-7 gene and its chromosomal mapping. Biochim Biophys Acta. 1998;1399:62–66. doi: 10.1016/s0167-4781(98)00094-3. et al. [DOI] [PubMed] [Google Scholar]
  • [26].Bashamboo A, Ferraz-de-Souza B, Lourenço D. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet. 2010;87:505–512. doi: 10.1016/j.ajhg.2010.09.009. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Kunimoto K, Yamazaki Y, Nishida T. Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet. Cell. 2012;148:189–200. doi: 10.1016/j.cell.2011.10.052. et al. [DOI] [PubMed] [Google Scholar]
  • [28].Ottolenghi C, Fellous M, Barbieri M. Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination. Genomics. 2002;79:333–343. doi: 10.1006/geno.2002.6711. et al. [DOI] [PubMed] [Google Scholar]
  • [29].Ivell R, Hunt N, Khan-Dawood F. Expression of the human relaxin gene in the corpus luteum of the menstrual cycle and in the prostate. Mol Cell Endocrinol. 1989;66:251–255. doi: 10.1016/0303-7207(89)90037-3. et al. [DOI] [PubMed] [Google Scholar]
  • [30].Wissmann M, Yin N, Müller JM. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol. 2007;9:347–353. doi: 10.1038/ncb1546. et al. [DOI] [PubMed] [Google Scholar]
  • [31].Fagerberg L, Hallström BM, Oksvold P. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13:397–406. doi: 10.1074/mcp.M113.035600. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Kim JW, Chang EM, Song SH. Complex chromosomal rearrangements in infertile males: complexity of rearrangement affects spermatogenesis. Fertil Steril. 2011;95:349–352. doi: 10.1016/j.fertnstert.2010.08.014. et al. 352.e1-5. [DOI] [PubMed] [Google Scholar]
  • [33].Ferlin A, Arredi B, Foresta C. Genetic cause of male infertility. Reprod Toxicol. 2006;22:133–141. doi: 10.1016/j.reprotox.2006.04.016. [DOI] [PubMed] [Google Scholar]
  • [34].Callier P, Faivre L, Marle N. Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12) (q24;q24) Eur J Med Genet. 2007;50:455–464. doi: 10.1016/j.ejmg.2007.06.004. et al. [DOI] [PubMed] [Google Scholar]
  • [35].Rouen A, Carlier L, Heide S. Potential selection of genetically balanced spermatozoa based on the hypo-osmotic swelling test in chromosomal rearrangement carriers. Reprod Biomed Online. 2017;35:372–378. doi: 10.1016/j.rbmo.2017.06.017. et al. [DOI] [PubMed] [Google Scholar]
  • [36].Matsuda T, Horii Y, Ogura K. Chromosomal survey of 1001 subfertile males: incidence and clinical features of males with chromosomal anomalies. Hinyokika Kiyo. 1992;38:803–809. et al. [PubMed] [Google Scholar]
  • [37].Kyu Lim C, Hyun Jun J, Mi Min D. Efficacy and clinical outcome of preimplantation genetic diagnosis using FISH for couples of reciprocal and Robertsonian translocations: the Korean experience. Prenat Diagn. 2004;24:556–561. doi: 10.1002/pd.923. et al. [DOI] [PubMed] [Google Scholar]
  • [38].Dutta UR, Rajitha P, Pidugu VK. Cytogenetic abnormalities in 1162 couples with recurrent miscarriages in southern region of India: report and review. J Assist Reprod Genet. 2011;28:145–149. doi: 10.1007/s10815-010-9492-6. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Rouen A, Pyram K, Pollet-Villard X. Simultaneous cell by cell study of both DNA fragmentation and chromosomal segregation in spermatozoa from chromosomal rearrangement carriers. J Assist Reprod Genet. 2013;30:383–390. doi: 10.1007/s10815-012-9915-7. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Ko DS, Cho JW, Park SY. Clinical outcomes of preimplantation genetic diagnosis (PGD) and analysis of meiotic segregation modes in reciprocal translocation carriers. Am J Med Genet A. 2010;152A:1428–1433. doi: 10.1002/ajmg.a.33368. et al. [DOI] [PubMed] [Google Scholar]
  • [41].Castle D, Bernstein R. Cytogenetic analysis of 688 couples experiencing multiple spontaneous abortions. Am J Med Genet. 1988;29:549–556. doi: 10.1002/ajmg.1320290312. [DOI] [PubMed] [Google Scholar]
  • [42].Adamoli A, Bernardi F, Chiaffoni G. Reproductive failure and parental chromosome abnormalities. Hum Reprod. 1986;1:99–102. doi: 10.1093/oxfordjournals.humrep.a136368. et al. [DOI] [PubMed] [Google Scholar]
  • [43].Olszewska M, Barciszewska MZ, Fraczek M. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl. 2017;19:117–124. doi: 10.4103/1008-682X.168684. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Pellestor F, Sèle B, Jalbert H. Direct segregation analysis of reciprocal translocations: a study of 283 sperm karyotypes from four carriers. Am J Hum Genet. 1989;44:464–473. et al. [PMC free article] [PubMed] [Google Scholar]
  • [45].Perrin A, Nguyen MH, Bujan L. DNA fragmentation is higher in spermatozoa with chromosomally unbalanced content in men with a structural chromosomal rearrangement. Andrology. 2013;1:632–638. doi: 10.1111/j.2047-2927.2013.00100.x. et al. [DOI] [PubMed] [Google Scholar]
  • [46].Antonelli A, Gandini L, Petrinelli P. Chromosomal alterations and male infertility. J Endocrinol Invest. 2000;23:677–683. doi: 10.1007/BF03343793. et al. [DOI] [PubMed] [Google Scholar]
  • [47].Bourrouillou G, Colombies P, Dastugue N. Chromosome studies in 2136 couples with spontaneous abortions. Hum Genet. 1986;74:399–401. doi: 10.1007/BF00280493. [DOI] [PubMed] [Google Scholar]
  • [48].Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod. 2006;21:1076–1082. doi: 10.1093/humrep/dei417. [DOI] [PubMed] [Google Scholar]
  • [49].Brugnon F, Van Assche E, Verheyen G, Sion B. Study of two markers of apoptosis and meiotic segregation in ejaculated sperm of chromosomal translocation carrier patients. Hum Reprod. 2006;21:685–693. doi: 10.1093/humrep/dei401. et al. [DOI] [PubMed] [Google Scholar]
  • [50].Douet-Guilbert N, Bris MJ, Amice V. Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature. Int J Androl. 2005;28:372–379. doi: 10.1111/j.1365-2605.2005.00571.x. et al. [DOI] [PubMed] [Google Scholar]
  • [51].Findikli N, Kahraman S, Kumtepe Y. Embryo development characteristics in Robertsonian and reciprocal translocations: a comparison of results with non-translocation cases. Reprod Biomed Online. 2003;7:563–571. doi: 10.1016/s1472-6483(10)62073-1. et al. [DOI] [PubMed] [Google Scholar]
  • [52].Gekas J, Thepot F, Turleau C. Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men. Hum Reprod. 2001;16:82–90. doi: 10.1093/humrep/16.1.82. et al. [DOI] [PubMed] [Google Scholar]
  • [53].Anton E, Vidal F, Blanco J. Reciprocal translocations: tracing their meiotic behavior. Genet Med. 2008;10:730–738. doi: 10.1097/GIM.0b013e318187760f. [DOI] [PubMed] [Google Scholar]
  • [54].Dul EC, van Echten-Arends J, Groen H. Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes. Hum Reprod. 2012;27:2850–2856. doi: 10.1093/humrep/des222. et al. [DOI] [PubMed] [Google Scholar]
  • [55].Iyer P, Wani L, Joshi S. Cytogenetic investigations in couples with repeated miscarriages and malformed children: report of a novel insertion. Reprod Biomed Online. 2007;14:314–321. doi: 10.1016/s1472-6483(10)60873-5. et al. [DOI] [PubMed] [Google Scholar]
  • [56].Sugiura-Ogasawara M, Aoki K, Fujii T. Subsequent pregnancy outcomes in recurrent miscarriage patients with a paternal or maternal carrier of a structural chromosome rearrangement. J Hum Genet. 2008;53:622–628. doi: 10.1007/s10038-008-0290-2. et al. [DOI] [PubMed] [Google Scholar]
  • [57].Pundir J, Magdalani L, El-Toukhy T. Outcome of preimplantation genetic diagnosis using FISH analysis for recurrent miscarriage in low-risk reciprocal translocation carriers. Eur J Obstet Gynecol Reprod Biol. 2016;203:214–219. doi: 10.1016/j.ejogrb.2016.05.053. [DOI] [PubMed] [Google Scholar]
  • [58].Gaboon NE, Mohamed AR, Elsayed SM. Structural chromosomal abnormalities in couples with recurrent abortion in Egypt. Turk J Med Sci. 2015;45:208–213. doi: 10.3906/sag-1310-5. et al. [DOI] [PubMed] [Google Scholar]
  • [59].Martin RH. Meiotic segregation of human sperm chromosomes in translocation heterozygotes: report of a t(9;10)(q34;q11) and a review of the literature. Cytogenet Cell Genet. 1988;47:48–51. doi: 10.1159/000132504. [DOI] [PubMed] [Google Scholar]
  • [60].Martin RH, Barclay L, Hildebrand K. Cytogenetic analysis of 400 sperm from three translocation heterozygotes. Hum Genet. 1990;86:33–39. doi: 10.1007/BF00205168. et al. [DOI] [PubMed] [Google Scholar]
  • [61].Martin RH. Sperm chromosome analysis of two men heterozygous for reciprocal translocations: t(1;9) (q22;q31) and t(16;19)(q11.1;q13.3) Cytogenet Cell Genet. 1992;60:18–21. doi: 10.1159/000133285. [DOI] [PubMed] [Google Scholar]
  • [62].Martin RH, Spriggs EL. Sperm chromosome complements in a man heterozygous for a reciprocal translocation 46,XY,t(9;13) (q21.1;q21.2) and a review of the literature. Clin Genet. 1995;47:42–46. doi: 10.1111/j.1399-0004.1995.tb03920.x. [DOI] [PubMed] [Google Scholar]
  • [63].Pellestor F, Girardet A, Coignet L. Cytogenetic analysis of meiotic segregation in sperm from two males heterozygous for reciprocal translocations using PRINS and humster techniques. Cytogenet Cell Genet. 1997;78:202–208. doi: 10.1159/000134657. et al. [DOI] [PubMed] [Google Scholar]
  • [64].Honda H, Miharu N, Ohashi Y. Analysis of segregation and aneuploidy in two reciprocal translocation carriers, t(3;9) (q26.2;q32) and t(3;9)(p25;q32), by triple-color fluorescence in situ hybridization. Hum Genet. 1999;105:428–436. doi: 10.1007/s004390051126. et al. [DOI] [PubMed] [Google Scholar]
  • [65].Estop AM, Cieply K, Munne S. Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies. Hum Genet. 2000;106:517–524. doi: 10.1007/s004390000275. et al. [DOI] [PubMed] [Google Scholar]
  • [66].Pellestor F, Imbert I, Andréo B. Study of the occurrence of interchromosomal effect in spermatozoa of chromosomal rearrangement carriers by fluorescence in-situ hybridization and primed in-situ labelling techniques. Hum Reprod. 2001;16:1155–1164. doi: 10.1093/humrep/16.6.1155. et al. [DOI] [PubMed] [Google Scholar]
  • [67].Rives N, Jarnot M, Mousset-Siméon N. Fluorescence in situ hybridisation (FISH) analysis of chromosome segregation and interchromosomal effect in spermatozoa of a reciprocal translocation t(9,10)(q11;p11.1) carrier. J Hum Genet. 2003;48:535–540. doi: 10.1007/s10038-003-0072-9. et al. [DOI] [PubMed] [Google Scholar]
  • [68].Estop AM, Cieply KM, Wakim A. Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization. Cytogenet Cell Genet. 1998;83:193–198. doi: 10.1159/000015177. et al. [DOI] [PubMed] [Google Scholar]
  • [69].Morel F, Douet-Guilbert N, Le Bris MJ. Lack of intraindividual variation of unbalanced spermatozoa frequenciesfrom a 46,XY,t(9;22)(q21;q11.2) carrier: case report. Hum Reprod. 2004;19:2227–2230. doi: 10.1093/humrep/deh439. et al. [DOI] [PubMed] [Google Scholar]
  • [70].Benet J, Oliver-Bonet M, Cifuentes P. Segregation of chromosomes in sperm of reciprocal translocation carriers: a review. Cytogenet Genome Res. 2005;111:281–290. doi: 10.1159/000086901. et al. [DOI] [PubMed] [Google Scholar]
  • [71].Ferfouri F, Boitrelle F, Clément P. Can one translocation impact the meiotic segregation of another translocation? A sperm-FISH analysis of a 46,XY,t(1;16)(q21;p11.2),t(8;9) (q24.3;p24) patient and his 46,XY,t(8;9)(q24.3;p24) brother and cousin. Mol Hum Reprod. 2013;19:109–117. doi: 10.1093/molehr/gas048. et al. [DOI] [PubMed] [Google Scholar]
  • [72].Aydos SE, Tükün A. Infertility in a man with oligoasthenoteratozoospermia associated with nonrobertsonian translocation t(9;15)(p10;q10) Fertil Steril. 2006;86:1001. doi: 10.1016/j.fertnstert.2006.02.124. e7-9. [DOI] [PubMed] [Google Scholar]
  • [73].Moretti E, Pascarelli NA, Giannerini V. 18, X, Y aneuploidies and transmission electron microscopy studies in spermatozoa from five carriers of different reciprocal translocations. Asian J Androl. 2009;11:325–332. doi: 10.1038/aja.2008.31. et al. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [74].Wiland E, Zegało M, Kurpisz M. Interindividual differences and alterations in the topology of chromosomes in human sperm nuclei of fertile donors and carriers of reciprocal translocations. Chromosome Res. 2008;16:291–305. doi: 10.1007/s10577-007-1194-2. [DOI] [PubMed] [Google Scholar]
  • [75].Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 infertile males. Urol Int. 1997;58:166–176. doi: 10.1159/000282975. [DOI] [PubMed] [Google Scholar]
  • [76].Escudero T, Abdelhadi I, Sandalinas M. Predictive value of sperm fluorescence in situ hybridization analysis on the outcome of preimplantation genetic diagnosis for translocations. Fertil Steril. 2003;3:1528–1534. doi: 10.1016/s0015-0282(03)00252-8. et al. 79 Suppl. [DOI] [PubMed] [Google Scholar]
  • [77].Perrin A, Caer E, Oliver-Bonet M. DNA fragmentation and meiotic segregation in sperm of carriers of a chromosomal structural abnormality. Fertil Steril. 2009;92:583–589. doi: 10.1016/j.fertnstert.2008.06.052. et al. [DOI] [PubMed] [Google Scholar]
  • [78].Celep F, Karagüzel A, Ozeren M. The frequency of chromosomal abnormalities in patients with reproductive failure. Eur J Obstet Gynecol Reprod Biol. 2006;127:106–109. doi: 10.1016/j.ejogrb.2005.12.019. et al. [DOI] [PubMed] [Google Scholar]
  • [79].Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol. 1998;81:171–176. doi: 10.1016/s0301-2115(98)00185-7. [DOI] [PubMed] [Google Scholar]
  • [80].Gada Saxena S, Desai K, Shewale L. Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure. Reprod Biomed Online. 2012;25:209–218. doi: 10.1016/j.rbmo.2012.04.004. et al. [DOI] [PubMed] [Google Scholar]
  • [81].Zhang Y, Zhu S, Wu J. Quadrivalent asymmetry in reciprocal translocation carriers predicts meiotic segregation patterns in cleavage stage embryos. Reprod Biomed Online. 2014;29:490–498. doi: 10.1016/j.rbmo.2014.06.010. et al. [DOI] [PubMed] [Google Scholar]

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