title: Med1 regulates meiotic progression during spermatogenesis in mice.
abstract: Spermatogenesis is a highly coordinated process. Signaling from nuclear hormone receptors, like those for retinoic acid (RA), is important for normal spermatogenesis. However, the mechanisms regulating these signals are poorly understood. Mediator complex subunit 1 (MED1) is a transcriptional enhancer that directly modulates transcription from nuclear hormone receptors. MED1 is present in male germ cells throughout mammalian development, but its function during spermatogenesis is unknown. To determine its role, we generated mice lacking Med1 specifically in their germ cells beginning just before birth. Conditional Med1 knockout males are fertile, exhibiting normal testis weights and siring ordinary numbers of offspring. RA-responsive gene products stimulated by RA gene 8 (Stra8) and synaptonemal complex protein 3 (Sycp3) are first detected in knockout spermatogonia at the expected time points during the first wave of spermatogenesis, and persist with normal patterns of cellular distribution in adult knockout testes. Meiotic progression, however, is altered in the absence of Med1. At postnatal day 7 (P7), zygotene-stage knockout spermatocytes are already detected, unlike in control testes, with fewer pre-leptotene-stage cells and more leptotene spermatocytes observed in the knockouts. At P9, Med1 knockout spermatocytes prematurely enter pachynema. Once formed, greater numbers of knockout spermatocytes remain in pachynema relative to the other stages of meiosis throughout testis development and its maintenance in the adult. Meiotic exit is not inhibited. We conclude that MED1 regulates the temporal progression of primary spermatocytes through meiosis, with its absence resulting in abbreviated pre-leptotene, leptotene, and zygotene stages, and a prolonged pachytene stage.
authors.affiliation: Driskill Graduate ProgramDepartment of PathologyDepartments of Pediatrics and Obstetrics and GynecologyNorthwestern University Feinberg School of Medicine and Human Molecular Genetics Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, PO Box 211, Chicago, Illinois 60611, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Huszar
authors.affiliation: Driskill Graduate ProgramDepartment of PathologyDepartments of Pediatrics and Obstetrics and GynecologyNorthwestern University Feinberg School of Medicine and Human Molecular Genetics Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, PO Box 211, Chicago, Illinois 60611, USA.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Driskill Graduate ProgramDepartment of PathologyDepartments of Pediatrics and Obstetrics and GynecologyNorthwestern University Feinberg School of Medicine and Human Molecular Genetics Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, PO Box 211, Chicago, Illinois 60611, USA.
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.affiliation: Driskill Graduate ProgramDepartment of PathologyDepartments of Pediatrics and Obstetrics and GynecologyNorthwestern University Feinberg School of Medicine and Human Molecular Genetics Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, PO Box 211, Chicago, Illinois 60611, USA Driskill Graduate ProgramDepartment of PathologyDepartments of Pediatrics and Obstetrics and GynecologyNorthwestern University Feinberg School of Medicine and Human Molecular Genetics Program, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Avenue, PO Box 211, Chicago, Illinois 60611, USA c-payne@northwestern.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Payne
mesh_terms: D000818:Animals; D008297:Male; D056913:Mediator Complex Subunit 1 / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D049471:Pachytene Stage / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism
chemical_list: C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1