Production of offspring after sperm chromosome screening: an experiment using the mouse model
Authors: Watanabe, H.; Kusakabe, H.; Mori, H.; Yanagimachi, R.; Tateno, H.
Source: Human Reproduction, Volume 28, Number 2, 28 February 2013 , pp. 531-537(7)
Publisher: Oxford University Press
Abstract:STUDY QUESTIONIs it possible to produce offspring after sperm chromosome screening?SUMMARY ANSWERIt is possible to produce zygotes after examining the genome of individual spermatozoa prior to embryo production.WHAT IS KNOWN ALREADYChromosomal aberrations in gametes are a major cause of pregnancy loss in women treated with assisted reproductive technology. However, to our knowledge, there are no reports on the successful genomic screening of spermatozoa, although some attempts have been made using the mouse as a model.STUDY DESIGNTo prevent the transmission of chromosomal aberrations from fathers to offspring, we performed sperm chromosome screening (SCS) prior to fertilization using the mouse as a model. The production of offspring after SCS consists of (i) replication of the sperm chromosomes, (ii) analysis of one copy of the replicated sperm chromosomes, (iii) construction of a zygote using another set of chromosomes and (iv) production of a transferable embryo.MATERIALS, SETTING, METHODSA single spermatozoon of a male mouse, with or without a Robertsonian translocation, was injected into an enucleated oocyte to allow the replication of sperm chromosomes. One of the sister blastomeres of a haploid androgenic 2-cell embryo was used for chromosome analysis. The other blastomere was fused with an unfertilized oocyte, activated and allowed to develop to a blastocyst before transfer to a surrogate mother.MAIN RESULTS AND ROLE OF CHANCEWith high efficiency, we were able to analyze sperm chromosomes in a blastomere from the androgenic 2-cell embryos and culture zygotes, with and without aberrant chromosomes, to the blastocyst stage before embryo transfer. The karyotypes of the offspring faithfully reflected those of the blastomeres used for SCS.LIMITATIONS, REASONS FOR CAUTIONThis study was conducted using a mouse model; whether or not the method is applicable to humans is not known.WIDER IMPLICATIONS OF THE FINDINGSThis study has shown that it is possible to produce zygotes without any paternally inherited aberrations by examining the genome of individual spermatozoa prior to embryo production.STUDY FUNDING/COMPETING INTERESTSThis study was supported by a Grants-in-Aid for Scientific Research (22·8495 and 23890013 to H.W.) from the Japan Society for the Promotion of Science (JSPS). There are no conflicts of interest to be declared.
Document Type: Research article
Publication date: 2013-02-28
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.