Wasserkanäle in Spermien von Mäusen und Menschen - molekulare Identifikation und physiologische Bedeutung in der Volumenregulation
Zusammenfassung der Projektergebnisse
Since mammalian spermatozoa leaving the testis encounter increasing osmolality in the epididymis during maturation and storage and are challenged by the decrease in osmolality in the female tract fluids upon ejaculation, cell volume regulation is a crucial sperm function in in vivo fertilisation. The present work has identified at physiological and molecular levels the water channels/transporters involved in this process. Among the candidates of such water channels/transporters, aquaporin (AQP) family members were implicated in sperm swelling experiments using various inhibitors. Based on published databases of the rat and mouse testis and our own present results, the aquaporins family members for sperm AQPs are limited to AQP7, AQP8 and AQPll. The nucleotide sequences of the open reading frames of these sperm aquaporin mRNAs in mouse and human were demonstrated for the first fime to be identical to those of somatic cells published in GenBank database, with shorter variance for HAQPS. AQP7 is unlikely to play a major role as sperm from Aqp knockout mice show normal basal cell volume, volume regulation and normal quinine swelling effect. However, bolh water efflux and influx occurted faster in these sperm than the wild type, which was explainable by an up-regulation ofAqpS expression revealed by quantitative PCR. As AQP8 is present all along the sperm tail whereas AQPll only at the tip of the tail, and swelling in sperm with blocked RVD (regulatory volume decrease) occurs at the mid-piece/principal piece junction causing angulation of the tail, it is most likely that AQP8 is the major aquaporin responsible for water fluxes during volume regulation. This could explain the present clinical finding that AQP8 expression by ejaculated sperm was inversely correlated with sperm coiling, which is a swelling phenomenon. On the other hand, correlation of AQP7 expression and progressive motility suggests a role of this aquaporin in sperm glycerol metabolism, which warrants further investigation. The association of AQPll with the residual cytoplasm of elongated spermatids and the distal tail of spermatozoa support the hypothesis of a role in the turnover of surplus cellular components and the maintenance of a functional germinal epithelium. These novel findings provide basis for further study of the role of AQPs in testicular and sperm function as well as clinical significance.
Projektbezogene Publikationen (Auswahl)
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Channels for water efflux and influx involved in volume regulation of murine spermatozoa. Reproduction 136, 401-410. (2008)
Callies C, TG Cooper, CH Yeung
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Aquaporin isoforms involved in physiological volume regulation of murine spermatozoa. Biol Reprod 80, 350-357. (2009)
Yeung CH, Callies C, Rojek A, Nielsen S, Cooper TG
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Coiled sperm from infertile patients - characteristics, associated factors and biological implication. Human Reproduction, (2009)
Yeung CH, Tüttelmann F, Bergmann M, Nordhoff V, Vorona E, Cooper TG
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Aquaporin AQP11 in the testis - molecular identity and association with the processing of residual cytoplasm of elongated spermatids
C.H. Yeung and T.G. Cooper
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Aquaporins in the human testis and spermatozoa - identification, involvement in sperm volume regulation and clinical relevance. Human Reproduclion, (2009)
Yeung CH, Callies C, Tüttelmann F, Kliesch S, Cooper TG
