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• W2106205257 abstract "FSH mediates cyclic follicle growth and development and is widely used for controlled ovarian stimulation in women undergoing infertility treatment. The ovarian response of women to FSH is variable, ranging from poor response to ovarian hyperstimulation.We investigated whether genetic alterations of the FSH receptor (FSHR) contribute to this variability.Our approach was to study women undergoing treatment with in vitro fertilization falling into the edges of the normal distribution of ovarian response to FSH, with respect to age.We conducted the study at the Yale Fertility Clinic.We extracted RNA from cumulus cells surrounding the oocytes of women undergoing in vitro fertilization and analyzed the FSHR mRNA by RT-PCR and sequencing.We identified four abnormal FSHR splicing products (three exon deletions and one intron insertion) in the FSHR mRNA in 37% (13 of 35) of women tested. All alterations affected the extracellular ligand-binding portion of the receptor without causing a frameshift. When transfected in HEK293T cells, all four splicing variants showed markedly decreased cAMP activation compared to controls. Untransfected cells showed no response to FSH, whereas all the cell lines showed normal cAMP activation when treated with forskolin, a nonreceptor-mediated cAMP stimulant. None of the normal or mutant forms showed any response to LH or TSH.Our findings strongly indicate FSHR variants as being an intrinsic genetic cause of some forms of infertility and identify a need for functional characterization of these variants and the investigation of more individualized ovarian stimulation protocols." @default.
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• W2106205257 date "2010-02-01" @default.
• W2106205257 modified "2023-10-17" @default.
• W2106205257 title "Identification and<i>in Vitro</i>Characterization of Follicle Stimulating Hormone (FSH) Receptor Variants Associated with Abnormal Ovarian Response to FSH" @default.
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• W2106205257 doi "https://doi.org/10.1210/jc.2009-1304" @default.
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