Fragile X syndrome is caused by a trinucleotide repeat expansion in the FMR1 gene. The premutation state is defined as 55-200 CGG repeats and associated with increased risk of premature ovarian failure (POF).
Aim: To assess the possible association between FMR1 mRNA expression levels in granulose cells and ovarian response among FMR1 premutation carriers.
The study population consisted of 19 FMR1 premutation carriers admitted for IVF-PGD treatment. The control group consists of 14 patients, matched by age, undergoing IVF-ICSI for male factor infertility. Follicular fluids containing granulose cells were collected from each patient. FMR1 mRNA levels were measured using Real-time quantitative PCR.
Results: The number of retrieved oocytes was significantly lower in premutation carriers compared to control (7.2±4.2 vs. 13.4±5.8, p<0.001). Moreover, a significant negative correlation was observed between the FMR1 mRNA levels and the number of oocytes retrieved (R= -0.58, p<0.01). There was a significant association between the levels of FMR1 mRNA (R2 = 0.366, p = 0.007) and the number of CGG repeats to the number of oocyte retrieved (R2 = 0.535, p < 0.0001). The lowest number of retrieved oocytes and the highest level of mRNA were seen in women with mid-size CGG repeats (78-117).
Conclusions: Diminished ovarian reserve is restricted to FMR1 premutation carriers with mid-range (78-117) CGG repeats. Furthermore, in these unique patients there are increased FMR1 mRNA levels in granulose cells. We speculate that mRNA toxicity plays a role is the pathophysiology of FMR1 related POF.
