title: The Effect of D-Aspartate on Spermatogenesis in Mouse Testis.
abstract: Spermatogenesis is controlled by hormonal secretions from the hypothalamus and pituitary gland, by factors produced locally in the testis, and by direct interaction between germ cells and Sertoli cells in seminiferous tubules. Although the mammalian testis contains high levels of D-aspartate (D-Asp), and D-Asp is known to stimulate the secretion of testosterone in cultured Leydig cells, its role in testis is unclear. We describe here biochemical, immunohistochemical, and flow cytometric studies designed to elucidate developmental changes in testicular D-Asp levels and the direct effect of D-Asp on germ cells. We found that the concentration of D-Asp in mouse testis increased with growth and that fluctuations in D-Asp levels were controlled in part by its degradative enzyme, D-aspartate oxidase expressed in Sertoli cells. In vitro sperm production studies showed that mitosis in premeiotic germ cells was strongly inhibited by the addition of D-Asp to the culture medium. Moreover, immunohistochemical analysis demonstrated that d-Asp accumulated in the differentiated spermatids, indicating either transport of D-Asp to spermatids or its de novo synthesis in these cells. Such compartmentation seems to prevent premeiotic germ cells in mouse testis from being exposed to the excess amount of D-Asp. In concert, our results indicate that in mouse testis, levels of D-Asp are regulated in a spatiotemporal manner and that D-Asp functions as a modulator of spermatogenesis.
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Shiga, Japan tanakah@belle.shiga-med.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kageyama
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagasawa
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Wada
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Murai
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Hanada
authors.affiliation: Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
authors.affiliation: Department of Urology, Shiga University of Medical Science, Otsu, Shiga, Japan kawauchi@belle.shiga-med.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawauchi
mesh_terms: D000818:Animals; D026603:D-Aspartic Acid / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D026603:D-Aspartic Acid
keywords: D-aspartate; Sertoli cell; spermatogenesis; testis