FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency

Shai E. Elizur, Olga Dratviman-Storobinsky, Sanaz Derech-Haim, Oshrit Lebovitz, Jehoshua Dor, Raoul Orvieto, Yoram Cohen

Research output: Contribution to journalArticlepeer-review

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 RNAs 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.

Original languageEnglish
Pages (from-to)334-337
Number of pages4
JournalGynecological Endocrinology
Volume32
Issue number4
DOIs
StatePublished - 2 Apr 2016

Keywords

  • FMR1 premutation
  • FXPOI
  • long non-coding RNA

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