FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2200979885> ?p ?o ?g. }

• W2200979885 endingPage "e8" @default.
• W2200979885 startingPage "e7" @default.
• W2200979885 abstract "ObjectiveBRCA1 and BRCA2 (BRCA1/2) genes are members of the ATM-mediated DNA repair pathway and are essential for DNA double strand break (DSB) repair. Multiple studies associated BRCA1/2 mutations with earlier natural menopause, lower serum AMH and low response to ovarian stimulation compared to BRCA1/2 mutation negative women, suggesting a role for BRCA1/2 genes in maintaining ovarian reserve. Additional evidence showed the age-related impairment in DSB repair might be a cause of normal oocyte aging and follicular depletion. We hypothesized that the deficient DNA DSB repair functions in BRCA1/2 mutation carriers, may lead to increased DNA DSBs and premature depletion of primordial follicles.DesignControlled laboratory study.Materials and MethodsUnder IRB approval, 230 BRCA1/2 carrier females with risk-reducing oophorectomies were identified from the pathology archive of a university hospital, and 25 met the inclusion criteria (<40 years old and absence of cancer diagnosis, ovarian pathology, prior chemotherapy or radiation exposure). These were age-matched with healthy ovaries harvested from organ donor cadavers (n=11), which served as controls.The paraffin fixed ovarian specimens were sectioned at 5μm thickness, and stained with hematoxylin and eosin to calculate the primordial follicle density, as well as with an anti-γH2AX antibody to identify DNA DSBs in these follicles. From each ovary, ten 50μm apart serial sections were blindly evaluated. Primordial follicles were counted only in the sections nuclei present to avoid double counting. The mean and standard error values were compared by Student’s t-test.ResultsThere were 17 cases with BRCA1 and 8 with BRCA2 mutations. All ovaries from BRCA1/2 mutation carriers and organ donor cadavers were disease free. Ovaries from BRCA1/2 mutation carriers (age 24-40 years, median 37) had significantly lower mean primordial follicle density compared to the controls (11±2 vs 23±6 follicles/mm3 ovarian cortex, p<0.05). When percentage of follicles that stain for γH2AX were compared, BRCA1/2 group showed significantly increased DNA DSBs in primordial follicles (62%±7% vs 22%±12%, p<0.05). There was no difference in primordial follicle density (11±2 vs 13±2, p=0.71) or γH2AX staining (63%±8% vs 61%±25%, p=0.96) between the BRCA1 and BRCA2 subgroups.ConclusionsThis is the first controlled study demonstrating diminished ovarian reserve in healthy BRCA1/2 mutation ovaries. Our results support and strengthen the previous studies that ovarian reserve is diminished in BRCA1/2 mutation carriers. As a novel finding, primordial follicles from these carriers have greater tendency for incurring DSBs. These results also vouch for the role of DNA DSB repair in maintaining ovarian reserve. The reduction in primordial follicle density may be due to premature attrition induced by lethal DNA damage. In addition to furthering our understanding of ovarian aging, our data may be useful when counseling BRCA1/2 mutation carriers about fertility planning. ObjectiveBRCA1 and BRCA2 (BRCA1/2) genes are members of the ATM-mediated DNA repair pathway and are essential for DNA double strand break (DSB) repair. Multiple studies associated BRCA1/2 mutations with earlier natural menopause, lower serum AMH and low response to ovarian stimulation compared to BRCA1/2 mutation negative women, suggesting a role for BRCA1/2 genes in maintaining ovarian reserve. Additional evidence showed the age-related impairment in DSB repair might be a cause of normal oocyte aging and follicular depletion. We hypothesized that the deficient DNA DSB repair functions in BRCA1/2 mutation carriers, may lead to increased DNA DSBs and premature depletion of primordial follicles. BRCA1 and BRCA2 (BRCA1/2) genes are members of the ATM-mediated DNA repair pathway and are essential for DNA double strand break (DSB) repair. Multiple studies associated BRCA1/2 mutations with earlier natural menopause, lower serum AMH and low response to ovarian stimulation compared to BRCA1/2 mutation negative women, suggesting a role for BRCA1/2 genes in maintaining ovarian reserve. Additional evidence showed the age-related impairment in DSB repair might be a cause of normal oocyte aging and follicular depletion. We hypothesized that the deficient DNA DSB repair functions in BRCA1/2 mutation carriers, may lead to increased DNA DSBs and premature depletion of primordial follicles. DesignControlled laboratory study. Controlled laboratory study. Materials and MethodsUnder IRB approval, 230 BRCA1/2 carrier females with risk-reducing oophorectomies were identified from the pathology archive of a university hospital, and 25 met the inclusion criteria (<40 years old and absence of cancer diagnosis, ovarian pathology, prior chemotherapy or radiation exposure). These were age-matched with healthy ovaries harvested from organ donor cadavers (n=11), which served as controls.The paraffin fixed ovarian specimens were sectioned at 5μm thickness, and stained with hematoxylin and eosin to calculate the primordial follicle density, as well as with an anti-γH2AX antibody to identify DNA DSBs in these follicles. From each ovary, ten 50μm apart serial sections were blindly evaluated. Primordial follicles were counted only in the sections nuclei present to avoid double counting. The mean and standard error values were compared by Student’s t-test. Under IRB approval, 230 BRCA1/2 carrier females with risk-reducing oophorectomies were identified from the pathology archive of a university hospital, and 25 met the inclusion criteria (<40 years old and absence of cancer diagnosis, ovarian pathology, prior chemotherapy or radiation exposure). These were age-matched with healthy ovaries harvested from organ donor cadavers (n=11), which served as controls.The paraffin fixed ovarian specimens were sectioned at 5μm thickness, and stained with hematoxylin and eosin to calculate the primordial follicle density, as well as with an anti-γH2AX antibody to identify DNA DSBs in these follicles. From each ovary, ten 50μm apart serial sections were blindly evaluated. Primordial follicles were counted only in the sections nuclei present to avoid double counting. The mean and standard error values were compared by Student’s t-test. ResultsThere were 17 cases with BRCA1 and 8 with BRCA2 mutations. All ovaries from BRCA1/2 mutation carriers and organ donor cadavers were disease free. Ovaries from BRCA1/2 mutation carriers (age 24-40 years, median 37) had significantly lower mean primordial follicle density compared to the controls (11±2 vs 23±6 follicles/mm3 ovarian cortex, p<0.05). When percentage of follicles that stain for γH2AX were compared, BRCA1/2 group showed significantly increased DNA DSBs in primordial follicles (62%±7% vs 22%±12%, p<0.05). There was no difference in primordial follicle density (11±2 vs 13±2, p=0.71) or γH2AX staining (63%±8% vs 61%±25%, p=0.96) between the BRCA1 and BRCA2 subgroups. There were 17 cases with BRCA1 and 8 with BRCA2 mutations. All ovaries from BRCA1/2 mutation carriers and organ donor cadavers were disease free. Ovaries from BRCA1/2 mutation carriers (age 24-40 years, median 37) had significantly lower mean primordial follicle density compared to the controls (11±2 vs 23±6 follicles/mm3 ovarian cortex, p<0.05). When percentage of follicles that stain for γH2AX were compared, BRCA1/2 group showed significantly increased DNA DSBs in primordial follicles (62%±7% vs 22%±12%, p<0.05). There was no difference in primordial follicle density (11±2 vs 13±2, p=0.71) or γH2AX staining (63%±8% vs 61%±25%, p=0.96) between the BRCA1 and BRCA2 subgroups. ConclusionsThis is the first controlled study demonstrating diminished ovarian reserve in healthy BRCA1/2 mutation ovaries. Our results support and strengthen the previous studies that ovarian reserve is diminished in BRCA1/2 mutation carriers. As a novel finding, primordial follicles from these carriers have greater tendency for incurring DSBs. These results also vouch for the role of DNA DSB repair in maintaining ovarian reserve. The reduction in primordial follicle density may be due to premature attrition induced by lethal DNA damage. In addition to furthering our understanding of ovarian aging, our data may be useful when counseling BRCA1/2 mutation carriers about fertility planning. This is the first controlled study demonstrating diminished ovarian reserve in healthy BRCA1/2 mutation ovaries. Our results support and strengthen the previous studies that ovarian reserve is diminished in BRCA1/2 mutation carriers. As a novel finding, primordial follicles from these carriers have greater tendency for incurring DSBs. These results also vouch for the role of DNA DSB repair in maintaining ovarian reserve. The reduction in primordial follicle density may be due to premature attrition induced by lethal DNA damage. In addition to furthering our understanding of ovarian aging, our data may be useful when counseling BRCA1/2 mutation carriers about fertility planning." @default.
• W2200979885 created "2016-06-24" @default.
• W2200979885 creator A5029028902 @default.
• W2200979885 creator A5034098587 @default.
• W2200979885 creator A5039267089 @default.
• W2200979885 creator A5072243585 @default.
• W2200979885 date "2015-09-01" @default.
• W2200979885 modified "2023-10-16" @default.
• W2200979885 title "BRCA1/2 gene mutations are associated with diminished primordial follicle density and increased oocyte DNA damage in the human ovary" @default.
• W2200979885 doi "https://doi.org/10.1016/j.fertnstert.2015.07.023" @default.
• W2200979885 hasPublicationYear "2015" @default.
• W2200979885 type Work @default.
• W2200979885 sameAs 2200979885 @default.
• W2200979885 citedByCount "0" @default.
• W2200979885 crossrefType "journal-article" @default.
• W2200979885 hasAuthorship W2200979885A5029028902 @default.
• W2200979885 hasAuthorship W2200979885A5034098587 @default.
• W2200979885 hasAuthorship W2200979885A5039267089 @default.
• W2200979885 hasAuthorship W2200979885A5072243585 @default.
• W2200979885 hasBestOaLocation W22009798851 @default.
• W2200979885 hasConcept C102570824 @default.
• W2200979885 hasConcept C104317684 @default.
• W2200979885 hasConcept C126322002 @default.
• W2200979885 hasConcept C134018914 @default.
• W2200979885 hasConcept C143425029 @default.
• W2200979885 hasConcept C16685009 @default.
• W2200979885 hasConcept C196843134 @default.
• W2200979885 hasConcept C2776690073 @default.
• W2200979885 hasConcept C2778324911 @default.
• W2200979885 hasConcept C2780536345 @default.
• W2200979885 hasConcept C501734568 @default.
• W2200979885 hasConcept C54355233 @default.
• W2200979885 hasConcept C5512455 @default.
• W2200979885 hasConcept C552990157 @default.
• W2200979885 hasConcept C71924100 @default.
• W2200979885 hasConcept C86803240 @default.
• W2200979885 hasConcept C87073359 @default.
• W2200979885 hasConceptScore W2200979885C102570824 @default.
• W2200979885 hasConceptScore W2200979885C104317684 @default.
• W2200979885 hasConceptScore W2200979885C126322002 @default.
• W2200979885 hasConceptScore W2200979885C134018914 @default.
• W2200979885 hasConceptScore W2200979885C143425029 @default.
• W2200979885 hasConceptScore W2200979885C16685009 @default.
• W2200979885 hasConceptScore W2200979885C196843134 @default.
• W2200979885 hasConceptScore W2200979885C2776690073 @default.
• W2200979885 hasConceptScore W2200979885C2778324911 @default.
• W2200979885 hasConceptScore W2200979885C2780536345 @default.
• W2200979885 hasConceptScore W2200979885C501734568 @default.
• W2200979885 hasConceptScore W2200979885C54355233 @default.
• W2200979885 hasConceptScore W2200979885C5512455 @default.
• W2200979885 hasConceptScore W2200979885C552990157 @default.
• W2200979885 hasConceptScore W2200979885C71924100 @default.
• W2200979885 hasConceptScore W2200979885C86803240 @default.
• W2200979885 hasConceptScore W2200979885C87073359 @default.
• W2200979885 hasIssue "3" @default.
• W2200979885 hasLocation W22009798851 @default.
• W2200979885 hasOpenAccess W2200979885 @default.
• W2200979885 hasPrimaryLocation W22009798851 @default.
• W2200979885 hasRelatedWork W1982656190 @default.
• W2200979885 hasRelatedWork W2045822318 @default.
• W2200979885 hasRelatedWork W2068375641 @default.
• W2200979885 hasRelatedWork W2114542496 @default.
• W2200979885 hasRelatedWork W2148951415 @default.
• W2200979885 hasRelatedWork W2164328274 @default.
• W2200979885 hasRelatedWork W2172100709 @default.
• W2200979885 hasRelatedWork W2542832879 @default.
• W2200979885 hasRelatedWork W3151884350 @default.
• W2200979885 hasRelatedWork W178837743 @default.
• W2200979885 hasVolume "104" @default.
• W2200979885 isParatext "false" @default.
• W2200979885 isRetracted "false" @default.
• W2200979885 magId "2200979885" @default.
• W2200979885 workType "article" @default.