The Impact of FMR۱ Gene Mutations on Fertility in Women with Type ۲ Epithelial Ovarian Cancer: A Case-Control Study Including Hormonal Assessments and Gene Expression Analysis

Introduction Type ۲ epithelial ovarian cancer (EOC) is a serious gynecological cancer with a complex etiology involving genetic, hormonal, and environmental factors. The FMR۱ gene, linked to fragile X syndrome, is associated with various reproductive and developmental disorders. Recent studies indicate that mutations in the FMR۱ gene may affect ovarian function and fertility, though their specific impact on women with type ۲ EOC is unclear. This study investigates the relationship between FMR۱ gene mutations and fertility in women with type ۲ EOC, utilizing hormonal assessments and gene expression analysis. Materials and Methods This case-control study involved ۲۰۰ women: ۱۰۰ diagnosed with type ۲ EOC and ۱۰۰ healthy controls. The average ages were ۴۵.۲ years for the case group and ۴۴.۷ years for the control group. Blood samples were collected to measure serum levels of reproductive hormones, including estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Hormonal profiles were analyzed to detect any endocrine disruptions linked to FMR۱ mutations. RNA was extracted from peripheral blood mononuclear cells (PBMCs) to measure the expression levels of the FMR۱ gene and related genes using quantitative real-time PCR (qRT-PCR). Expression data were normalized and analyzed using comparative threshold cycle (Ct) methods. Results The study revealed significant differences in hormonal profiles and gene expression between the case and control groups. Estrogen levels were lower in the case group (۴۵.۳ pg/mL) compared to the control group (۶۰.۲ pg/mL), and progesterone levels were ۳.۱ ng/mL versus ۵.۷ ng/mL, respectively. In contrast, FSH levels were higher in the case group (۱۲.۸ mIU/mL) compared to controls (۷.۴ mIU/mL), as were LH levels (۱۰.۵ mIU/mL vs. ۶.۸ mIU/mL). Gene expression analysis showed elevated FMR۱ expression in the case group (۱.۸ relative units) compared to controls (۱.۰ relative units). Similarly, BRCA۱ and P۵۳ expressions were higher in the case group, with ۲.۴ and ۳.۲ relative units, respectively, versus ۱.۰ in the control group. These findings indicate lower estrogen and progesterone levels, alongside higher FSH and LH levels, in women with type ۲ EOC. Furthermore, there was increased expression of FMR۱, BRCA۱, and P۵۳ genes in these patients. Conclusion This study suggests that FMR۱ mutations are linked to altered hormonal profiles and increased expression of genes related to ovarian function and cancer in women with type ۲ EOC. The observed hormonal imbalances and elevated gene expressions highlight the complex interaction between genetic factors and ovarian cancer pathology. Further research is needed to explore these associations and develop targeted therapies to improve fertility outcomes in women with type ۲ EOC.

کلیدواژه ها:

FMR۱ gene ، Type ۲ epithelial ovarian cancer ، Fertility ، Case-control study