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Research Article |
Institute for Biogenesis Research,4 John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96822
Division of Developmental Genetics,5 MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
ABSTRACT
In mouse and man, Y chromosome deletions are frequently associated with spermatogenic defects. XYTdym1qdelSry 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. XYRIIIqdel 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 YTdym1qdel 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 XYRIIIqdel 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) YRIIIqdel 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.
assisted reproductive technology, gamete biology, in vitro fertilization, sperm, spermatogenesis
1 Supported by Hawaii State Biomedical Research Infrastructure Network grant P20 RR16467 and Victoria S. and Bradley L. Geist Foundation grant 20031970 to M.A.W.
2 Correspondence: Monika A. Ward, Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, 1960 East-West Road, Honolulu, HI 96822. FAX: 808 956 7316; mward{at}hawaii.edu
3 Monika A. Ward previously published manuscripts under the name Monika A. Szczygiel.
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