| Chromosome polymorphism is the minor differences in the chromosome morphology between human groups. In traditional genetic view, chromosome polymorphism usually does not have obvious phenotypic or pathological significance. But a growing number of studies have shown that chromosome polymorphism could produce clinical effects, and was related to reproductive abnormalities, such as early recurrent spontaneous abortion, early embryo growth arrest, fetal malformations and so on.Big Y chromosome is a common chromosome polymorphism. While according to previous statistics, the percentage of big Y chromosome in the male patients of reproductive abnormalities is up to 2.18%-21.73%. With the increasing development of assisted reproductive technology, many infertile patients resort to in vitro fertilization-embryo transfer technology, including many patients of big Y chromosome.There were few studies on the formation mechanism of big Y chromosome. The prenatal and postnatal diagnosis of the fetal Yassmine made a study of were Yqh+/Yqh- chimera, which meant there were two cell populations involving Y chromosome heterochromatin of differing lengths in the same individual. It was explained that a postzygotic simple deletion or unequal crossover event between sister chromatids in the DYZ region has occured. The results suggested the formation of big Y chromosome may be closely associated with DYZ region. DYZ stands for human Y-chromosome specific repeated DNA family, including DYZ1, DYZ2 and DYZ3 so far. DYZ1 is the major tandem repeat sequence of Y chromosome distal heterochromatin, accounting for almost 40% of total length of Y chromosome. DYZ1 is made up of 3.6 kb, and 2000-4000 repetitions in normal male. Comparing DYZ1 genomic instability of men exposed to radiation with that of male patients of recurrent spontaneous abortion (RSA), Deepali found the latter was more common, suggesting DYZ1 may play a key role in the Y chromosome folding and structural integrity.Based on the above concept, at first, we studied the effect of big Y chromosome on in vitro fertilization-embryo transfer outcome by a retrospective clinical study. Then, DYZ1 integrity and copy number variation in patients of Y chromosome polymorphism and recurrent spontaneous abortion were studied to detect whether DYZ1 may play a key role in Y chromosome polymorphism and early recurrent spontaneous abortion.Section 1 Effect of big Y chromosome on in vitro fertilization-embryo transfer outcomeOBJECTIVES The effect of big Y chromosome on in vitro fertilization embryo transfer outcome was studied by a retrospective clinical study.METHODS In vitro fertilization-fresh embryo transfer cycles completed at Reproductive Medical Center of Provincial Hospital Affiliated to Shandong University from January 2006 to December 2008 were selected. In big Y group (33 patients and 47 treatment cycles total), the male chromosome of the patients were big Y by G-banding and their wives were excluded of known diseases which may influence the outcome of in vitro fertilization-embryo transfer; while in the control group, all other 6620 treatment cycles of the same period were involved. RESULTS There was no significant difference between the big Y group and the control group in fertilization rate, cleavage rate, good-quality embryo rate, embryo imbed rate, pregnancy rate and early abortion rate(P＞0.05), but the ratios of deformed babies and female at birth were higher in the big Y group(P＜0.05).CONCLUSIONS In conventional in vitro fertilization and embryo transfer cycles, there is no significant difference in embryonic development and recent pregnancy outcome between patients with the big Y chromosome and normal patients. Women whose husbands have big Y chromosome undergoing conventional in vitro fertilization embryo transfer cycles are more likely to give birth to girls.Section 2 DYZ1 stability, Y chromosome polymorphism and early recurrent spontaneous abortionOBJECTIVES DYZ1 integrity and copy number variation in patients of Y chromosome polymorphism and recurrent spontaneous abortion were studied to detect whether DYZ1 play a key role in Y chromosome polymorphism and early recurrent spontaneous abortion.METHODS DYZ1 of the male patients resorted to our center at the same period was selected to study. Among them, unexplained early RSA male patients were 106 cases; patients of Y chromosome polymorphism were 86 cases, including big Y patients (Y≥chromosome 18) 79 cases and small Y patients (Y≤chromosome 21) 7 cases; men at the same period who had at least one normal birth and were excluded of chromosome abnormalities were 100 cases.RESULTS After PCR and electrophoresis, of RSA patients,1 case showed deletion of 266 bp from 25 to 290 bp and 2 cases showed deletion of 773bp from 1347 to 2119 bp; of small Y patients,2 cases showed deletion of 266 bp from 25 to 290 bp, 4 cases showed deletion of 773bp from 1347 to 2119 bp and 275 bp from 3128 to 3420 bp; while big Y patients and normal fertile men were found no part missing of DYZ1. By real-time fluorescent quantitative PCR, in normal fertile men, the mean of DYZ1 copies was 3900; big Y patients for 5571, significantly different (P＜0.007) when compared with normal fertile men which means DYZ1 copy number in patients of big Y chromosome was more than that of the normal fertile men; RSA patients for 2655, significantly different (P＜0.001) when compared with normal fertile men which means DYZl copy number in unexplained early RSA patients was less than that of the normal fertile men; small Y patients for 1059, significantly different (P＜0.001) when compared with normal fertile men which means DYZ1 copy number in small Y patients was less than that of the normal fertile men.CONCLUSIONS More DYZ1 copy number may increase the visible length of Y-chromosome under the microscope, and there is a close relation between reduced length of Y chromosome under the microscope and DYZl part deletion, while the decrease of DYZ1 copy number within normal range may be a cause of early recurrent spontaneous abortion. |
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