title: FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency.
abstract: The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. The highest level of FMR6 was seen in women with mid-size CGG repeats (80-120). In addition, a significant negative linear correlation was observed between the number of oocytes retrieved and the RNA levels in granulosa cells of FMR6 (r = -0.53, p = 0.01) but not FMR4. Our study supports previous findings suggesting RNA toxic gain-of-function as one of the possible pathophysiologic mechanisms underlying FXPOI.
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Shai E
authors.initials: SE
authors.lastname: Elizur
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Dratviman-Storobinsky
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Derech-Haim
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Oshrit
authors.initials: O
authors.lastname: Lebovitz
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Jehoshua
authors.initials: J
authors.lastname: Dor
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Raoul
authors.initials: R
authors.lastname: Orvieto
authors.affiliation: a IVF Unit, Department of Obstetrics and Gynecology , Chaim Sheba Medical Center , (Tel Hashomer) , Ramat Gan , Israel and.|b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D016649:Primary Ovarian Insufficiency / Q000209:etiology* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012313:RNA; D062085:RNA, Long Noncoding; C497683:FMR1 protein, human; C000613323:long non-coding RNA FMR4, human; C000613324:long non-coding RNA FMR6, human
keywords: FMR1 premutation; FXPOI; long non-coding RNA