title: Mice overexpression of human augmenter of liver regeneration (hALR) in male germ cells shows abnormal spermatogenesis and reduced fertility.
abstract: Human augmenter of liver regeneration (hALR) is a sulfhydryl oxidase that is highly expressed in spermatogonia and early spermatocytes.  To investigate the physiological effects of hALR in spermatogenesis, we generated a hALR transgenic mouse model driven by the human TSPY (testis-specific protein, Y-encoded) promoter that allows the transgene to be specifically activated in the testes.  hALR content was found to be increased in both germ cells.  The histological and TUNEL analysis of transgenic testes revealed a number of spermatogenetic defects including primary spermatocyte overpopulation followed by depletion through apoptosis, degenerating and detached nucleated germ cells, haploid cell loss and intraepithelial vacuoles of varying sizes.  In line with these features, adult transgenic male mice also displayed a reduction in fertility.  Our data suggest that regulated spatial and temporal expression of hALR is required for normal testicular development and spermatogenesis, and overexpression of hALR results in influencing the sperm morphology and quantity and the eventual reduction in male fertility.  Present findings in the mouse may be of interest to human male fertility.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Fu
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Ge
authors.forename: Wang-Xiang
authors.initials: WX
authors.lastname: Xu
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Zhan
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yang
mesh_terms: D000818:Animals; D003579:Cytochrome Reductases / Q000096:biosynthesis*; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009845:Oligospermia; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000378:metabolism
chemical_list: D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors