[Analysis of synaptonemal complex from a carrier with 46,XY,t(11;18) balanced translocation]

Over ten years ago, two male patients of pregnancy wastage, who were the carriers of 4;6 and 4;13 reciprocal translocations, respectively, were analyzed with synaptonemal complexes (SCs) by de Perdigo et al. They suggested that the pregnancy wastage should be caused by heterosynapsis, which reciprocal translocations resulted in. The heterosynapsis might avoid spermatogenesis failure, but easily induced non-disjunction of some chromosomes and led to occurrence of unbalanced gametes. A new male patient of the pregnancy wastage was detected in China three years ago. Karyotyping of the patient showed 11;18 reciprocal translocation. Analysis of synaptonemal complexes (SCs) of the patient was performed using the EM technology of SC surface spreading, SDS treatment, AgNO3 staining. The SCs of 30 spermatocytes at pachytenes were analyzed. The SCs in electron micrographs were measured by the method published by de Perdigo et al. (1991). The results showed that each of the observed spermatocytes displayed 20 autosomal bivalents, a quadrivalent 11;18 and a sexual bivalent. Of the 30 spermatocytes, 21 each exhibited a quadrivalent of adequate quality for measurement and interpretation. The 21 quadrivalents were classified into three types: type I, quadrivalents with fully paired arms with the expected cross-configuration, two quadrivalents were of this type. Type II, quadrivalents with an evident heterosynapsis, forming five SC segments (four fully pairing arms and one middle pairing region), six quadrivalents were of this type. Type III, quadrivalents with four paired arms, but with asynapsed regions around the breakpoints, thirteen quadrivalents were of this type. Based on configuration, quadrivalents were classified into cis-configuration with above three types and trans-configuration with above two types except type I. Each of the analyzed quadrivalents showed four synaptic arms, which respectively paired between chromosome 11 and t18 (the translocated 18;11), 18 and t18, 18 and t11 (the translocated 11;18), and 11 and t11, and the arms were designated as A, B, C, and D correspondingly. The measurements of A and D as well as B and C observed in different cells were taken by calculating the percentages of their lengths in comparison to the length of chromosome 11 and 18, respectively. So were the middle synaptic regions. Measurements of SCs revealed that the location of the putative breakpoints estimated from the fully paired quadrivalents were different from those determined by G-band analysis for mitotic chromosomes. The length of the paired and unpaired segments varied from one quadrivalent to another. For instance, in the case of fully paired A and D arms, the breakpoint was located near to 45.59% and 38.53% of the length of the normal chromosome 11, the breakpoint from the mitotic chromosome was estimated to be near to 45%. The location of the putative breakpoints estimated from the No. 1 quadrivalent was consistent with the breakpoint from the mitotic chromosome. This suggested that only this quadrivalent showed complete homologous pairing. Obviously, the lengths of middle pairing region in type II quadrivalent were different from one quadrivalent to another. The middle pairing region/the length of the normal chromosome 11 is 4.11% - 18%, that/the length of the normal chromosome 18 is 8% - 41.1%. The middle pairing regions should be the heterologous pairing regions in quadrivalents. The quadrivalents with unsynaptic regions also showed partially heterologous synapsis. In 14 of 21 quadrivalents, the paired regions overlapped the mitotic breakpoint position in chromosome 11. In 20 of 21 quadrivalents, the paired regions overlapped the chromosome 18 of mitotic breakpoint position in one or two arms. As synapsis can proceed homologously only up to the breakpoints, a heterosynapsis apparently occurred in 20 quadrivalents. The length of the paired and unpaired segments varied from one quadrivalent to another, and the measurements of the arms of the quadrivalents could not be used to determine breakpoints. The unpaired segment showed a thick and sometimes a split aspect similar to that of the sexual bivalent. Of the 20 quadrivalents with heterosynapsis, four were at early pachytene stages, fourteen at the middle and two at the late, respectively. The heterosynapsis, which occurred on the early pachytene, was without previous homosynapsis. This was different from the classical "synaptic adjustment" during the late pachrtene of spermatocytes. Many researches on reciprocal translocation associated with pregnancy wastage have been reported. It is most possible that the wastage detected in this study was related to the t(11;18). Normal synapsis finishes at early pachytene, while in the observed proband, most of the quadrivalents still left unsynaptic parts during middle and late pachytene stages. Obviously, the synapsis was delayed or incomplete. The unsynaptic regions distributed mainly in the central regions. The central regions perhaps completed the synapsis more late, therefore they had more chances to leave the unsynaptic parts. In addition, the results of SC analysis showed that heterosynapsis occurred wildly and was exhibited from early to late pachytene stages. It has been reported that crossing over could be inhibited by heterosynapsis in mice, man and boar, and normal segregation needs existence of crossing over. Therefore, heterosynapsis may interfere in normal segregation. Both unsynapsis and heterosynapsis could induce incidence of unbalanced gametes. In general, the unbalanced gametes are lethal and could not take part in fertilization, once they fertilize with normal eggs, the risk of pregnancy wastage or other genetic disorders will exist certainly. Our results showed that the heterosynapsis occurred widely, so a poor risk of pregnancy wastages caused by reciprocal translocation probably is not unusual.