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- W4387403734 abstract "BRCA1 and 2 are the most common genetic mutations in hereditary breast cancer. Women with BRCA1 and 2 mutations have been shown to have a diminished primordial follicle density and increased oocyte DNA damage, but studies did not differentiate between BRCA1 and 2. Our objectives include: 1. Determine primordial and primary follicle density in BRCA1 and BRCA2 carriers compared to age matched controls. 2. Identify markers of DNA damage in oocytes of BRCA1 and BRCA2 carriers compared to age matched controls. We performed a retrospective case-control study using ovarian tissue from patients age 18-40 with a BRCA1 or 2 mutation who underwent risk-reducing bilateral salpingo-oophorectomy. Samples from age matched controls who underwent unilateral or bilateral oophorectomies were collected. Exclusion criteria included ovarian cancer, prior chemotherapy or radiation, ovarian pathology including endometriosis, or postmenopausal status. Multiple Formalin-fixed and paraffin-embedded tissue blocks were sectioned and stained with hematoxylin and eosin and follicles counted by two blinded counters. Immunohistochemical analysis of phosphorylated histone H2AX (γH2AX) and phospho-ATM (p-ATM) were used to assess DNA double strand breaks. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for oocyte apoptosis was performed. Statistical analysis was performed in Graphpad Prism. One way ANOVA with Tukey’s multiple comparisons test was used for all tests except for follicle density which was analyzed with two-way ANOVA with Tukey’s multiple comparisons test. A total of 30 subjects were included: 8 BRCA1, 9 BRCA2, and 13 controls. There were no significant differences in mean age. Only BRCA1 carriers had a statistically significant decrease in primordial follicle density compared to controls (p=0.036). Neither BRCA group had altered primary follicle density compared to controls. BRCA1 carriers had a statistically higher percentage of p-ATM positivity compared to controls (63.3% vs 42.6%, p=0.134). BRCA2 carriers had a higher p-ATM positivity compared to controls but it was not statistically significant (57.9% vs 42.6%, p=0.066). Both BRCA groups had statistically significant higher positivity for γH2AX than controls (52.9% vs 31.0%, p=0.0002; 50.3% vs 31.0% p=0.0005). Both BRCA groups had higher levels of TUNEL positivity than controls, but it was not statistically significant (45.4% vs 32.8%, p=0.149; 46.2% vs 32.8%, p=0.105). BRCA1 carriers have significantly lower primordial follicle density and higher levels of oocyte DNA damage. Though BRCA2 carriers do not have a decrease in follicle density, they do have significantly higher levels of DNA damage." @default.
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- W4387403734 date "2023-10-01" @default.
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- W4387403734 title "THE EFFECTS OF THE BRCA1 AND 2 MUTATIONS ON OVARIAN RESERVE AND AGING" @default.
- W4387403734 doi "https://doi.org/10.1016/j.fertnstert.2023.08.083" @default.
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