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Biology of Reproduction 61, 1062-1069 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Articles

Infertile Spermatozoa of c-ros Tyrosine Kinase Receptor Knockout Mice Show Flagellar Angulation and Maturational Defects in Cell Volume Regulatory Mechanisms1

Ching-Hei Yeung2,a, Eva Sonnenberg-Riethmacherb, and Trevor G. Coopera

a Institute of Reproductive Medicine of the University, D-48129 Münster, Germany b Max-Delbrück Center of Molecular Medicine, D-13122 Berlin, Germany

Homozygous c-ros knockout male mice that lack prepubertal differentiation of the epididymal initial segment are healthy but sterile, despite normal sperm production and mating. Detailed computerized analysis of the motility of spermatozoa maturing in the epididymis revealed only minor defects. However, the majority of motile mature sperm released from the cauda epididymidis showed various extents of flagellar angulation that could not be corrected by raising extracellular osmolality. Measurement of the osmolality of cauda epididymal fluid showed no difference from the wild type. Studies in wild-type mice indicated a maturational change in the ability of motile sperm to maintain straight flagella during incubation, but angulation was induced in cauda sperm by the volume-sensitive ion channel blockers quinine, 5-nitro-2-(3-phenylpropylamino)-benzoic acid and BaCl2, or by exposure to hypotonic media. Flagellar angulation, induced in the wild type or intrinsic to the knockout, was relieved upon demembranation by Triton X-100, confirming that it was a cell swelling phenomenon. A lack of response of immature wild-type sperm and mature knockout sperm to the channel blockers suggests that there is normally a development of the volume regulatory mechanisms upon maturation that is defective in sperm from the knockout animal. The resultant flagellar angulation may account for the reduction in sperm numbers in the oviduct of mated females and the failure to fertilize in vivo.

1 The study was supported by the Deutsche Forschungsgemeinschaft Confocal Research Group "The Male Gamete: Production, Maturation, Function" (grant Ni-130/15).

2 Correspondence: C-H. Yeung, Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48129 Münster, Germany. FAX: 49 251 8356093; yeung{at}uni-muenster.de




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