Related Experiment Video
Updated: Aug 28, 2025

Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation
Published on: October 25, 2024
Granulosa Cell Dysfunction Is Associated With Diminished Ovarian Response in FMR1 Premutation Carriers
Ilana Boustanai1, Hila Raanani1, Adva Aizer1
1Sheba Medical Center Hospital-Tel Hashomer, Ramat-Gan 52621, Israel.
Context:
FMR1 premutation (PM) carriers are at increased risk of ovarian impairment resulting in diminished ovarian response (DOR) to exogenous follicle-stimulating hormone (FSH) stimulation. Expanded CGG repeat transcript and RAN-associated protein (FMRpolyG) have been shown to accumulate in cellular aggregates and sequester proteins, thus impairing their function. Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads involved in FSH receptor (FSHR) transcript maturation during FSH-dependent follicular development.
Objective:
The present study examined a possible pathophysiological explanation for DOR to exogenous FSH stimulation in FMR1 PM carriers.
Methods:
We used both a human granulosa cell (GC) line model and human GCs from FMR1 PM carriers to evaluate whether Sam68 is sequestered with expanded CGG repeat transcript.
Results:
We show that Sam68 is sequestered in GCs, most likely by interaction with the expanded CGG repeat transcript. The sequestration may lead to reduced levels of free Sam68 available for FHSR precursor transcript processing, causing dysregulation of FSHR transcript maturation, and a consequent decrease in FSHR protein levels.
Conclusion:
Sam68 sequestration may underlie the diminished ovarian response to FSH stimulation in FMR1 PM carriers.
More Related Videos
Related Concept Videos
Oogenesis
Folliculogenesis
Hormonal Control of the Ovarian Cycle
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
Menopause
Ovarian Cycle
Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...

