title: Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency.
abstract: Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI.
authors.affiliation: Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London (UCL) Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
authors.forename: Ranna
authors.initials: R
authors.lastname: El-Khairi
authors.forename: Rahul
authors.initials: R
authors.lastname: Parnaik
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Duncan
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Dianne
authors.initials: D
authors.lastname: Gerrelli
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
authors.forename: John C
authors.initials: JC
authors.lastname: Achermann
mesh_terms: D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000196:embryology* / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D013737:Testis / Q000196:embryology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins