STUDY OF PRIMORDIAL FOLLICLE, CORPORA LUTEA AND Fmr1 mRNA LEVELS FROM OVARIUM OF Fmr1 GENE PREMUTATION MICE

Abstract

Background : The FMR1 gene involves in fragile X-associated disorders (FAD), including the fragile X mental retardation syndrome, primary ovarian insufficiency (POI) and Fragile X associated tremor/ataxia syndrome. Primary ovarian insufficiency (POI) affect on 13-26% female premutation carrier, characterized by early depletion of ovarian follicles before the age of 40 years. The underlying mechanisms of POI are still unclear. This study focuses on number of primordial follicles, ovulation and ovarian Fmr1 mRNA levels in Fmr1 gene premutation mice as animal models. Method : This research was a cross sectional study using a Fmr1 gene premutation mice model (exCGG mice) and wt mice. The number of primordial follicles were determined at different ages (P6, P25, ~20wk, and ~40wk). The presence of recent corpora lutea (CL) were determined at ~20wk and ~40wk. Fmr1 mRNA levels in ovaries from P25 premutation mice were determined and compared to wild type (wt) mice. Results : Approximately a four fold elevated level of Fmr1 mRNA was found in ovaries of premutation mice. No differences in number of primordial follicles was found in ovaries from P6 and ~20wk premutation mice compared to wt mice (p=0.052 and p=0.515, respectively). Significant higher number of primordial follicles was found at P25, and ~40wk premutation mice compared to wt mice (p=0.018, and 0.006, respectively). Furthermore reduced ovulation, determined by presence of recent corpora lutea, in 20 and 40-week-old premutation mice was found. Conclusion : The fragile X premutation does not cause a reduction in the initial pool of primordial follicles from birth but might be involved in mechanisms influencing the folliculogenesis results in decreased ovulation. Keyword : Primary ovarian insufficiency (POI), FMR1 gene, FMRP, FMR1 mRNA, primordial follicle, folliculogenesis