FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve
dc.contributor.author | Rehnitz, Julia | pt_BR |
dc.contributor.author | Alcoba, Diego Duarte | pt_BR |
dc.contributor.author | Brum, Ilma Simoni | pt_BR |
dc.contributor.author | Dietrich, Jens Erik | pt_BR |
dc.contributor.author | Youness, Berthe | pt_BR |
dc.contributor.author | Hinderhofer, Katrin | pt_BR |
dc.contributor.author | Messmer, Birgitta | pt_BR |
dc.contributor.author | Freis, Alexander | pt_BR |
dc.contributor.author | Strowitzki, Thomas | pt_BR |
dc.contributor.author | Germeyer, Ariane | pt_BR |
dc.date.accessioned | 2019-04-26T02:38:15Z | pt_BR |
dc.date.issued | 2018 | pt_BR |
dc.identifier.issn | 1477-7827 | pt_BR |
dc.identifier.uri | http://hdl.handle.net/10183/193532 | pt_BR |
dc.description.abstract | 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. | en |
dc.format.mimetype | application/pdf | pt_BR |
dc.language.iso | eng | pt_BR |
dc.relation.ispartof | Reproductive biology and endocrinology. London. Vol. 16 (2018), 65, [9 p.] | pt_BR |
dc.rights | Open Access | en |
dc.subject | Insuficiência ovariana primária | pt_BR |
dc.subject | FMR1 expression | en |
dc.subject | Células da granulosa | pt_BR |
dc.subject | Granulosa cells | en |
dc.subject | FMR1 CGG repeat length | en |
dc.subject | Hormônio folículo estimulante | pt_BR |
dc.subject | FMR1 genotype | en |
dc.title | FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve | pt_BR |
dc.type | Artigo de periódico | pt_BR |
dc.identifier.nrb | 001074897 | pt_BR |
dc.type.origin | Estrangeiro | pt_BR |
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