TY  - JOUR
SN  - 1477-7827
A1  - Rehnitz, Julia
A1  - Alcoba, Diego D.
A1  - Brum, Ilma S.
A1  - Dietrich, Jens E.
A1  - Youness, Berthe
A1  - Hinderhofer, Katrin
A1  - Messmer, Birgitta
A1  - Freis, Alexander
A1  - Strowitzki, Thomas
A1  - Germeyer, Ariane
CY  - London
VL  - 16
IS  - 65
PB  - BioMed Central
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/24853/
AV  - public
Y1  - 2018///
TI  - FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve
SP  - 1
EP  - 9
JF  - Reproductive Biology and Endocrinology
N2  - 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 ??CT 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.
ID  - heidok24853
ER  -