title: FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve
creator: Rehnitz, Julia
creator: Alcoba, Diego D.
creator: Brum, Ilma S.
creator: Dietrich, Jens E.
creator: Youness, Berthe
creator: Hinderhofer, Katrin
creator: Messmer, Birgitta
creator: Freis, Alexander
creator: Strowitzki, Thomas
creator: Germeyer, Ariane
subject: 610
subject: 610 Medical sciences Medicine
description: Background: Fragile-X-Mental-Retardation-1- (FMR1)-gene is supposed to be a key gene for ovarian reserve and folliculogenesis. It contains in its 5’-UTR a triplet-base-repeat (CGG), that varies between 26 and 34 in general population. CGG-repeat-lengths with 55–200 repeats (pre-mutation = PM) show instable heredity with a tendency to increase and are associated with premature-ovarian-insufficiency or failure (POI/POF) in about 20%. FMR1-mRNA-expression in leucocytes and granulosa cells (GCs) increases with CGG-repeat-length in PM-carriers, but variable FMR1-expression profiles were also described in women with POI without PM-FMR1 repeat-length. Additionally, associations between low numbers of retrieved oocytes and elevated FMR1-expression levels have been shown in GCs of females with mid-range PM-CGG-repeats without POI. Effects of FMR1-repeat-lengths-deviations (n < 26 or n > 34) below the PM range (n < 55) on ovarian reserve and response to ovarian stimulation remain controversial.    Methods: We enrolled 229 women undergoing controlled ovarian hyperstimulation for IVF/ICSI-treatment and devided them in three ovarian-response-subgroups: Poor responder (POR) after Bologna Criteria, polycystic ovary syndrome (PCO) after Rotterdam Criteria, or normal responder (NOR, control group). Subjects were subdivided into six genotypes according to their be-allelic CGG-repeat length. FMR1-CGG-repeat-length was determined using ALF-express-DNA-sequencer or ABI 3100/3130 × 1-sequencer. mRNA was extracted from GCs after follicular aspiration and quantitative FMR1-expression was determined using specific TaqMan-Assay and applying the ΔΔCT method. Kruskall-Wallis-Test or ANOVA were used for simple comparison between ovarian reserve (NOR, POR or PCO) and CGG-subgroups or cohort demographic data. All statistical analysis were performed with SPSS and statistical significance was set at p ≤ 0.05.    Results: A statistically significant increase in FMR1-mRNA-expression-levels was detected in GCs of PORs with heterozygous normal/low-CGG-repeat-length compared with other genotypes (p = 0.044).       Conclusion: Female ovarian response may be negatively affected by low CGG-alleles during stimulation. In addition, due to a low-allele-effect, folliculogenesis may be impaired already prior to stimulation leading to diminished ovarian reserve and poor ovarian response. A better understanding of FMR1 expression-regulation in GCs may help to elucidate pathomechanisms of folliculogenesis disorders and to develop risk-adjusted treatments for IVF/ICSI-therapy. Herewith FMR1-genotyping potentially provides a better estimatation of treatment outcome and allows the optimal adaptation of stimulation protocols in future.
publisher: BioMed Central
date: 2018
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/24853/1/12958_2018_Article_383.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-248539
identifier:   Rehnitz, Julia ; Alcoba, Diego D. ; Brum, Ilma S. ; Dietrich, Jens E. ; Youness, Berthe ; Hinderhofer, Katrin ; Messmer, Birgitta ; Freis, Alexander ; Strowitzki, Thomas ; Germeyer, Ariane  (2018) FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve.  Reproductive Biology and Endocrinology, 16 (65).  pp. 1-9.  ISSN 1477-7827     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/24853/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng