The first FSHR frameshift mutation is reported here, and the first missense mutation in the signal peptide-encoding region of FSHR to be associated with POI.
Transplanted hAD-MSCs were only located in the interstitium of ovaries, rather than in follicles, and did not express the typical markers of oocytes and GCs, which are ZP3 and FSHR, respectively. hAD-MSCs secreted FGF2, IGF-1, HGF, and VEGF, and those growth factors were detected in the hAD-MSC-CM. hAD-MSC-CM injection improved the local microenvironment of POI ovaries, leading to a decrease in Bax expression and an increase in Bcl-2 and endogenous VEGF expression in ovarian cells, which inhibited chemotherapy-induced GC apoptosis, promoted angiogenesis and regulated follicular development, thus partly reducing ovarian injury and improving ovarian function in rats with POI.
Expression of the male-specific Sry gene in the ovarian tissues of POI + PBMCs + PRP female recipient rats was evident at 5, 10, and 20 days posttransplantation along with significant increases in the expression of angiogenesis markers CD34+ and VEGF and folliculogenesis markers AMH and FSHR.
After hPMSC transplantation, the AMH and FSHR expression in ovarian tissue was significantly higher than in the POF group as determined by immunochemistry and western blot analysis.
SDF-1/CXCR4 and FSHR expressed in ovaries were detected in the cytoplasm of preantral and antral follicles; the expression of SDF-1/CXCR4 was increased and FSHR was decreased in POF mice.
We found that Rg1 treatment up-regulated the expression of follicle stimulating hormone receptor and down-regulated senescence-associated protein expression in granule cells of POF mice.
In the present study, the single nucleotide polymorphisms (SNPs) of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), inhibin βB (INHBB) and follicle stimulating hormone receptor (FSHR) genes were investigated, and their association with POF in a Chinese Hui population of the Ningxia Hui Autonomous Region in western China was evaluated.
Inactivating mutations of FSH receptor are associated with partial to complete premature ovarian failure in women and variable impairment of spermatogenesis and small testes in men.
We observed a significant association between premature ovarian failure and the combined genetic effect of single nucleotide polymorphism (SNP) rs4646 (CA+AA) in the 3' untranslated region of CYP19A1 and the missense FSHR SNP rs6166 (AG+GG) genotype (odds ratio 5.42, 95% confidence interval 1.96-14.98), and we identified a significant association between premature ovarian failure and the combined genetic effect of the FSHR missense SNP rs6166 (AA) and the rs4646-rs10046 haplotype (C-T)+(C-C) (odds ratio 5.47, 95% confidence interval 2.03-14.75), suggesting that two biochemical pathways may be involved in the regulation of folliculogenesis.
FSHR inactivating mutations may cause primary or secondary amenorrhea, infertility, and premature ovarian failure (POF), whereas activating mutations can predispose to ovarian hyperstimulation syndrome (OHSS) as a consequence of exogenous FSH administration, or with a spontaneous onset.