The widespread production of mice with transgenes, disrupted genes and mutant genes, has strained the resources available for maintaining these mouse

Why, Oh Y?: The mammalian Y chromosome is a symbol of maleness and encodes genes important for male reproduction. Various deletions of the Y chromosome result in sperm defects and infertility. When haploid male germ cells were injected directly into oocytes, Yamauchi et al. (p. 69 , published online 21 November; see the Perspective by Capel ) found that living offspring could be derived from male mice whose Y chromosome contribution was limited to only two genes. These two genes are the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y .

Replacing the Y chromosome: The mammalian Y chromosome encodes a specialized set of genes that are essential for male viability and fertility. In particular, the sex-determining region Y (SRY) protein is necessary to initiate male sex determination. However, Yamauchi et al. show that the functions of the entire Y chromosome can be replaced with only two genes. In mice, two transgenes, Sox9 and Eif2s3x , compensated for the absence of all Y chromosome genes to allow successful sperm formation. Science , this issue p. 514

In mouse and man, Y chromosome deletions are frequently associated with spermatogenic defects. XY^Tdym1qdelSry males have an extensive Yq deletion that almost completely abolishes the expression of two gene families, Ssty and Sly, located within the male-specific region of the mouse Y long arm. These males exhibit severe sperm defects and sterility. XY^RIIIqdel males have a smaller interstitial Yq deletion, removing approximately two thirds of Ssty/Sly gene copies, and display an increased incidence of mild sperm head anomalies with impairment of fertility and an intriguing distortion in the sex ratio of offspring in favor of females. Here we used intracytoplasmic sperm injection (ICSI) to investigate the functional capacity of sperm from these Yq deletion males. Any selection related to the ability of sperm to fertilize in vitro is removed by ICSI, and we obtained two generations of live offspring from the infertile males. Genotyping of ICSI-derived offspring revealed that the Y^Tdym1qdel deletion does not interfere with production of Y chromosome-bearing gametes, as judged from the frequency of Y chromosome transmission to the offspring. ICSI results for XY^RIIIqdel males also indicate that there is no deficiency of Y sperm production in this genotype, although the data show an excess of females following in vitro fertilization and natural mating. Our findings suggest that 1) Yq deletions in mice do not bias the primary sex ratio and 2) Y^RIIIqdel spermatozoa have poorer fertilizing ability than their X-bearing counterparts. Thus, a normal complement of the Ssty and/or Sly gene families on mouse Yq appears necessary for normal sperm function. Summary: ICSI was successfully used to reproduce infertile mice with Yq deletions, and the analysis of sperm function in obtained offspring demonstrated that gene families located within the deletion interval are necessary for normal sperm function.

In spite of its highly condensed state, sperm DNA is vulnerable to damage that can originate from oxidative stress, the activity of sperm‐specific nucleases, or both. After fertilization, in the oocyte, paternal chromatin undergoes dramatic changes, and during this extensive remodeling, it can be both repaired and degraded, and these processes can be linked to DNA synthesis. Here, we analyzed sperm response to damage‐inducing treatments both before and after fertilization and before or after zygotic DNA replication. Epididymal mouse spermatozoa were either frozen without cryoprotection (FT) or treated with detergent Triton X‐100 coupled with dithiothreitol (TX+DTT) to induce DNA damage. Fresh, untreated sperm served as control. Immediately after preparation, spermatozoa from 3 groups were taken for comet assay, or for intracytoplasmic sperm injection into prometaphase I oocytes to visualize prematurely condensed single‐chromatid chromosomes, or into mature metaphase II oocytes to visualize chromosomes after DNA replication. Comet assay revealed increased DNA fragmentation in treated sperm when compared with control, with FT sperm more severely affected. Chromosome analysis demonstrated paternal DNA damage in oocytes injected with treated, but not with fresh, sperm, with FT and TX+DTT groups now yielding similar damage. There were no differences in the incidence of abnormal paternal karyoplates before and after DNA synthesis in all examined groups. This study provides evidence that subjecting sperm to DNA damage–inducing treatments results in degradation of highly condensed sperm chromatin when it is still packed within the sperm head, and that this DNA damage persists after fertilization. The difference in DNA damage in sperm subjected to 2 treatments was ameliorated in the fertilized oocytes, suggesting that some chromatin repair might have occurred. This process, however, was independent of DNA synthesis and took place during oocyte maturation.