Production of offspring after sperm chromosome screening: An experiment using the mouse model

Abstract

Study Question Is it possible to produce offspring after sperm chromosome screening? Summary Answer It 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 Design To 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, Method SA 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 Caution This 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 Interest SThis 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. © 2012 The Author.