title: LKB1 is an essential regulator of spermatozoa release during spermiation in the mammalian testis.
abstract: LKB1 acts as a master upstream protein kinase regulating a number of kinases involved in diverse cellular functions. Recent studies have suggested a role for LKB1 in male fertility. Male mice with reduced total LKB1 expression, including the complete absence of the major splice variant in testis (LKB1(S)), are completely infertile. We sought to further characterise these mice and determine the mechanism underlying this infertility. This involved expression studies of LKB1 in developing germ cells, morphological analysis of mature spermatozoa and histological studies of both the testis and epididymis using light microscopy and transmission electron microscopy. We conclude that a defect in the release of mature spermatids from the seminiferous epithelium (spermiation) during spermatozoan development is a major cause of the infertility phenotype. We also present evidence that this is due, at least in part, to defects in the breakdown of the junctions, known as ectoplasmic specialisations, between the sertoli cells of the testis epithelium and the heads of the maturing spermatids. Overall this study uncovers a critical role for LKB1 in spermiation, a highly regulated, but poorly understood process vital for male fertility.
authors.affiliation: Medical Research Council's Clinical Sciences Centre, Imperial College, London, United Kingdom.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Denison
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Muckett
authors.forename: Laura
authors.initials: L
authors.lastname: O'Hara
authors.forename: David
authors.initials: D
authors.lastname: Carling
authors.forename: Angela
authors.initials: A
authors.lastname: Woods
mesh_terms: D055372:AMP-Activated Protein Kinases; D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D007248:Infertility, Male / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases