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. 2014 Aug 25;9(8):e105121.
doi: 10.1371/journal.pone.0105121. eCollection 2014.

Elevated levels of FMR1 mRNA in granulosa cells are associated with low ovarian reserve in FMR1 premutation carriers

Shai E Elizur  1 , Oshrit Lebovitz  1 , Sanaz Derech-Haim  1 , Olga Dratviman-Storobinsky  1 , Baruch Feldman  1 , Jehoshua Dor  1 , Raoul Orvieto  1 , Yoram Cohen  1
Affiliations

Elevated levels of FMR1 mRNA in granulosa cells are associated with low ovarian reserve in FMR1 premutation carriers

Shai E Elizur et al. PLoS One. .

Abstract

Aim: To assess the role of mRNA accumulation in granulosa cells as the cause of low ovarian response among FMR1 premutation carriers undergoing pre-implantation genetic diagnosis (PGD).

Design: Case control study in an academic IVF unit. Twenty-one consecutive FMR1 premutation carriers and 15 control women were included. After oocyte retrieval the granulosa cells mRNA levels of FMR1 was measured using RT-PCR.

Results: In FMR1 premutation carriers, there was a significant non-linear association between the number of CGG repeats and the number of retrieved oocytes (p<0.0001) and a trend to granulosa cells FMR1 mRNA levels (p = 0.07). The lowest number of retrieved oocytes and the highest level of mRNA were seen in women with mid-size CGG repeats (80-120). A significant negative linear correlation was observed between the granulosa cells FMR1 mRNA levels and the number of retrieved oocytes (R2 linear = 0.231, P = 0.02).

Conclusion: We suggest that there is a no-linear association between the number of CGG repeats and ovarian function, resulting from an increased granulosa cells FMR1 mRNA accumulation in FMR1 carriers in the mid-range (80-120 repeats).

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. A non-linear association between the number of retrieved oocytes during IVF cycle and the number of CGG repeats in FMR1 premutation carriers (55–200 repeats).
(P<0.0001).
Figure 2
Figure 2. A trend for a non-linear association between FMR1 mRNA levels in granulosa cells of FMR1 premutation carriers (55–200 repeats) and the number of CGG repeats.
(P = 0.07).
Figure 3
Figure 3. The number of retrieved oocyte during IVF cycle according to mRNA levels of FMR1 in granulosa cells in FMR1 premutation carriers (55–200 repeats).
(R2 linear = 0.231, P = 0.02).
Figure 4
Figure 4. Methylated FMR1 DNA (%) in granulosa cells in women with normal CGG repeats (<55), premutation carriers (55–200) and full mutation (>200).
Figure 5
Figure 5. Methylated FMR1 DNA (%) in granulosa cells according to the number of CGG repeats in premutation carriers (55–200) and full mutation (>200).
See this image and copyright information in PMC

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