Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1980 Nov;32(6):833–848.

Genetically determined asynapsis, spermatogenic degeneration, and infertility in men.

R S Chaganti, S C Jhanwar, L T Ehrenbard, I A Kourides, J J Williams
PMCID: PMC1686144  PMID: 7446525

Abstract

We report a family in which azoospermia and infertility affected two sibs whose parents were first cousins once removed. Meiotic cells of the proband, who had the chromosomal complement of a normal male (46,XY), exhibited asynapsis, defective synaptonemal complex (SC) formation, chiasma failure, and degeneration of prophase spermatocytes with asynapsis. Based on these observations, we suggest that the meiotic abnormalities and infertility in this family comprise a trait with an autosomal recessive mode of inheritance. Review of published cases of infertile men with normal chromosomal complements and disturbed meiosis suggests that genetically determined asynapsis and desynapsis similar to that established in plant and insect species also occur in humans. In humans, asynapsis appears to be inherited as an autosomal recessive. The mode of inheritance of desynapsis is not clear; X-linked recessive or autosomal dominant has been suggested in one family. Studies by us and by others reported in the literature suggest that the mode of action of genes that affect synapsis and cause a reduction in the numbers of visible chiasmata at diakinesis is dissimilar to that of the action of genes that cause defective meiotic recombination, defective repair of induced damage to DNA in somatic cells, and chromosome instability.

Full text

PDF
833

Images in this article

840Fig. 5-12
on p.840
838Fig. 2-4
on p.838
842Fig. 13-15
on p.842
843Fig. 16-18
on p.843

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker B. S., Carpenter A. T., Esposito M. S., Esposito R. E., Sandler L. The genetic control of meiosis. Annu Rev Genet. 1976;10:53–134. doi: 10.1146/annurev.ge.10.120176.000413. [DOI] [PubMed] [Google Scholar]
  2. Beadle G. W., McClintock B. A GENIC DISTURBANCE OF MEIOSIS IN ZEA MAYS. Science. 1928 Nov 2;68(1766):433–433. doi: 10.1126/science.68.1766.433. [DOI] [PubMed] [Google Scholar]
  3. Bigos S. T., Ridgway E. C., Kourides I. A., Maloof F. Spectrum of pituitary alterations with mild and severe thyroid impairment. J Clin Endocrinol Metab. 1978 Feb;46(2):317–325. doi: 10.1210/jcem-46-2-317. [DOI] [PubMed] [Google Scholar]
  4. CARR D. H., WALKER J. E. Carbol fuchsin as a stain for human chromosomes. Stain Technol. 1961 Jul;36:233–236. doi: 10.3109/10520296109113278. [DOI] [PubMed] [Google Scholar]
  5. Carpenter A. T. Recombination nodules and synaptonemal complex in recombination-defective females of Drosophila melanogaster. Chromosoma. 1979;75(3):259–292. doi: 10.1007/BF00293472. [DOI] [PubMed] [Google Scholar]
  6. Chaganti R. S., German J. Human male infertility, probably genetically determined, due to defective meiosis and spermatogenic arrest. Am J Hum Genet. 1979 Sep;31(5):634–641. [PMC free article] [PubMed] [Google Scholar]
  7. Chandley A. C., Maclean N., Edmond P., Fletcher J., Watson G. S. Cytogenetics and infertility in man. II. Testicular histology and meiosis. Ann Hum Genet. 1976 Nov;40(2):165–176. doi: 10.1111/j.1469-1809.1976.tb00176.x. [DOI] [PubMed] [Google Scholar]
  8. Dutrillaux B., Guéguen J. Anomalies méiotiques et gamétiques multiples dans un cas de stérilité masculine. Ann Genet. 1971 Mar;14(1):49–52. [PubMed] [Google Scholar]
  9. EVANS E. P., BRECKON G., FORD C. E. AN AIR-DRYING METHOD FOR MEIOTIC PREPARATIONS FROM MAMMALIAN TESTES. Cytogenetics. 1964;3:289–294. doi: 10.1159/000129818. [DOI] [PubMed] [Google Scholar]
  10. Forejt J., Goetz P. Synaptonemal complexes of mouse and human pachytene chromosomes visualized by silver staining in air-dried preparations. Chromosoma. 1979 Aug 10;73(2):255–261. doi: 10.1007/BF00331576. [DOI] [PubMed] [Google Scholar]
  11. Gatti M. Genetic control of chromosome breakage and rejoining in Drosophila melanogaster: spontaneous chromosome aberrations in X-linked mutants defective in DNA metabolism. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1377–1381. doi: 10.1073/pnas.76.3.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillies C. B., Rasmussen S. W., von Wettstein D. The synaptinemal complex in homologous and nonhomologous pairing of chromosomes. Cold Spring Harb Symp Quant Biol. 1974;38:117–122. doi: 10.1101/sqb.1974.038.01.015. [DOI] [PubMed] [Google Scholar]
  13. Gowen J. W. MUTATION, CHROMOSOME NON-DISJUNCTION AND THE GENE. Science. 1928 Aug 31;68(1757):211–212. doi: 10.1126/science.68.1757.211. [DOI] [PubMed] [Google Scholar]
  14. Hodgkin J., Horvitz H. R., Brenner S. Nondisjunction Mutants of the Nematode CAENORHABDITIS ELEGANS. Genetics. 1979 Jan;91(1):67–94. doi: 10.1093/genetics/91.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hotta Y., Chandley A. C., Stern H. Biochemical analysis of meiosis in the male mouse. II. DNA metabolism at pachytene. Chromosoma. 1977 Jul 8;62(3):255–268. doi: 10.1007/BF00286047. [DOI] [PubMed] [Google Scholar]
  16. Hultén M., Eliasson R., Tillinger K. G. Low chiasma count and other meiotic irregularities in two infertile 46, XY men with spermatogenic arrest. Hereditas. 1970;65(2):285–290. doi: 10.1111/j.1601-5223.1970.tb02327.x. [DOI] [PubMed] [Google Scholar]
  17. Hultén M., Luciani J. M., Kirton V., Devictor-Vuillet M. The use and limitations of chiasma scoring with reference to human genetic mapping. Cytogenet Cell Genet. 1978;22(1-6):37–58. doi: 10.1159/000130917. [DOI] [PubMed] [Google Scholar]
  18. Hultén M., Solari A. J., Skakkebaek N. E. Abnormal synaptonemal complex in an oligochiasmatic man with spermatogenic arrest. Hereditas. 1974;78(1):105–116. doi: 10.1111/j.1601-5223.1974.tb01433.x. [DOI] [PubMed] [Google Scholar]
  19. Koulischer L., Schoysman R. Chromosomes and human infertility. I. Mitotic and meiotic chromosome studies in 202 consecutive male patients. Clin Genet. 1974;5(2):116–126. doi: 10.1111/j.1399-0004.1974.tb01673.x. [DOI] [PubMed] [Google Scholar]
  20. Kourides I. A., Weintraub B. D., Rosen S. W., Ridgway E. C., Kliman B., Maloof F. Secretion of alpha subunit of glycoprotein hormones by pituitary adenomas. J Clin Endocrinol Metab. 1976 Jul;43(1):97–106. doi: 10.1210/jcem-43-1-97. [DOI] [PubMed] [Google Scholar]
  21. Lehmann A. R., Kirk-Bell S., Arlett C. F., Harcourt S. A., de Weerd-Kastelein E. A., Keijzer W., Hall-Smith P. Repair of ultraviolet light damage in a variety of human fibroblast cell strains. Cancer Res. 1977 Mar;37(3):904–910. [PubMed] [Google Scholar]
  22. Miller O L. Cytological Studies in Asynaptic Maize. Genetics. 1963 Nov;48(11):1445–1466. doi: 10.1093/genetics/48.11.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pathak S., Hsu T. C. Silver-stained structures in mammalian meiotic prophase. Chromosoma. 1979 Jan 8;70(2):195–203. doi: 10.1007/BF00288406. [DOI] [PubMed] [Google Scholar]
  24. Pearson P. L., Ellis J. D., Evans H. J. A gross reduction in chiasma formation during meiotic prophase and a defective DNA repair mechanism associated with a case of human male infertility. Cytogenetics. 1970;9(6):460–467. doi: 10.1159/000130115. [DOI] [PubMed] [Google Scholar]
  25. Purnell D. J. Spontaneous univalence at male meiosis in the mouse. Cytogenet Cell Genet. 1973;12(5):327–335. doi: 10.1159/000130471. [DOI] [PubMed] [Google Scholar]
  26. Reame N. E., Hafez E. S. Hereditary defects affecting fertility. N Engl J Med. 1975 Mar 27;292(13):675–681. doi: 10.1056/NEJM197503272921306. [DOI] [PubMed] [Google Scholar]
  27. Skakkebaek N. E., Bryant J. I., Philip J. Studies on meiotic chromosomes in infertile men and controls with normak karyotypes. J Reprod Fertil. 1973 Oct;35(1):23–36. doi: 10.1530/jrf.0.0350023. [DOI] [PubMed] [Google Scholar]
  28. Smith P. A., King R. C. Genetic control of synaptonemal complexes in Drosophila melanogaster. Genetics. 1968 Oct;60(2):335–351. doi: 10.1093/genetics/60.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stern H., Hotta Y. Biochemical controls of meiosis. Annu Rev Genet. 1973;7:37–66. doi: 10.1146/annurev.ge.07.120173.000345. [DOI] [PubMed] [Google Scholar]
  30. Templado C., Marina S., Egozcue J. Three cases of low chiasma frequency associated with infertility in man. Andrologia. 1976;8(4):285–289. doi: 10.1111/j.1439-0272.1976.tb01657.x. [DOI] [PubMed] [Google Scholar]
  31. Thomson E., Fletcher J., Chandley A. C., Kucerová M. Meiotic and radiation studies in four oligochiasmatic men. J Med Genet. 1979 Aug;16(4):270–277. doi: 10.1136/jmg.16.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES