Study On The Relationship Between Chromosomal Structural Abnormality And Male Infertility, Abortion Or Stillbirth

BackgroundChromosome is the carrier of the genetic material (DNA), Chromosomenumber or structure abnormalities will lead to gene increased, deletion orrearrangement, resulting in abnormal fertility. In recent years, the majority of thepatients with reproductive anomalies for genetic counseling are male infertility,abortion or stillbirth. WHO data shows that30%～40%of male infertility is causedby genetic factors. The main genetic factors leading to male infertility arechromosomal abnormalities and Y chromosome microdeletions. The Incidence ofchromosomal abnormalities is2.2%～33%in infertile males. Y chromosomemicrodeletions are present in idiopathic azoospermia and oligozoospermiapatients, suggesting that Y chromosome microdeletions, which can causespermatogenic failure, may be an important genetic factor in idiopathic maleinfertility. One of the couple with chromosomal abnormalities is an importantcytogenetic factor causing abortion and stillbirth. The incidence of chromosomeabnormalities in the general population was0.5%, of reproductive abnormalitiescouples was7.41%, while in habitual abortion couples, it is as high as30%～60%. Chromosome number abnormalities are common, such as klinefeltersyndrome(47,XXY),turner syndrome(45,X). Chromosome structural abnormalitiesconsist of reciprocal translocation, Robertsonian translocation, inversions,deletions, duplication and ring chromosome. The carrier of chromosomestructural abnormalities can be expressed as infertility, abortion, stillbirth, givingbirth to congenital malformation or mental retardation children. In this paper, totally4679cases of male infertility, abortion or stillbirth were performed thecytogenetic analysis, including karyotype analysis, routine semen analysis,semen cytology analysis, serum reproductive hormones inspection and AZFgene detection, to study the relationship between chromosome reciprocaltranslocations, Robertsonian translocations, inversions, deletions, chromosomepolymorphism and male infertility, abortion, stillbirth, and provide theoretical andexperimental evidence for genetic counseling and treatment for these patients.Objective1. To evaluate the influence of chromosome reciprocal translocation, robertsoniantranslocation on male infertility patients with spermatogenic failure.2. To investigate the influence of Y chromosome microdeletions in male infertilitypatients.3. To study the impact of chromosome reciprocal translocation, robertsoniantranslocation on abortion stillbirth patients.4. To evaluate the relationship between chromosome polymorphism and maleinfertility, abortion, stillbirth.MethodsThe study population came from4679patients with reproductive abnormalityattending genetic consultancy in the Cell Biology Department, Clinical Hospital ofJilin University during2009.09-2012.10. The4679patients were made up of1374couples and1931infertile men.Karyotype analysis were performed on peripheralblood lymphocytes with standard G-banding.Multiplex polymerase chain reaction(PCR) amplification using nine specific sequencetagged sites (STS) were used todetect Y chromosome microdeletions. In addition, semen cytology analysis,serum reproductive hormones test were used especially for infertile males. Results1. Karyotype analysis was performed in4679patients, including1931maleinfertility patients and2748cases of abortion stillbirth patients (1374couples).Chromosomal abnormalities were found in400cases, the abnormal rate was8.5%(400/4679).2. In1931cases of male infertility patients, chromosomal abnormalities werefound in273cases, the positive rate was14.1%. Among them,185caseswere chromosome number abnormal,45cases were chromosome structureabnormal, and43cases were chromosome polymorphism. In273patientswith chromosome abnormality,203cases were azoospermia,58cases wereoligospermia,11cases were normal semen and1case not done.Besides, Ychromosome microdeletion was found in187cases of1931infertile males,the positive rate was9.7%(187/1931).3. In2748(1374couples) cases of abortion stillbirth patients, chromosomalabnormalities were found in127cases, the positive rate was4.6%. In1374cases of male patients,71cases with chromosomal abnormalities, the positiverate was5.2%(71/1374), including4cases with chromosome numberabnormality,28cases with chromosome structural abnormality,39cases withchromosome polymorphism. In1374cases of female patients,56cases withchromosome abnormality, the positive rate was4.1%(56/1374), including3cases with chromosome number abnormality,33cases with chromosomestructural abnormality,20cases with chromosome polymorphism.4.24cases of chromosomal polymorphism were recalled for family visit andkaryotype analysis.20probands had birth a phenotypically normal child,respectively; the proband14and17were still infertie as a result of Ychromosome microdeletion, and suggested using assisted reproductivetechnology for offspring; the proband2and6were still not fertile. Familie1~17of the proband showed male sterility; family18~24of the proband showed abortion stillbirth.Conclusions1. The positive rate of chromosome abnormality in male infertility, abortion orstillbirth patients was significantly higher than that of the general population.2. Chromosome reciprocal translocation may lead to the occurrence of malespermatogenesis dysfunction, abortion and stillbirth.3. Y chromosome microdeletion was another important cause in male infertility.4. Chromosomal breakpoints in1p32,1q42,12q13place will lead to malespermatogenesis dysfunction. Chromosomal breakpoints in8q24.3place willlead to spontaneous abortion. Chromosomal breakpoints in7q22,13q10,14q10,9q22place will result in spontaneous abortion and male infertility.5. There may be no correlation between the chromosome polymorphism andmale infertility, abortion, stillbirth.