Identification of a unique epigenetic profile in women with diminished ovarian reserve
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Identification of a unique epigenetic profile in women with diminished ovarian reserve. / Olsen, Kristina W.; Castillo-Fernandez, Juan; Chan, Andrew Cho; la Cour Freiesleben, Nina; Zedeler, Anne; Bungum, Mona; Cardona, Alexia; Perry, John R.B.; Skouby, Sven O.; Hoffmann, Eva R.; Kelsey, Gavin; Grøndahl, Marie Louise.
I: Fertility and Sterility, Bind 115, Nr. 3, 2021, s. 732-741.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Identification of a unique epigenetic profile in women with diminished ovarian reserve
AU - Olsen, Kristina W.
AU - Castillo-Fernandez, Juan
AU - Chan, Andrew Cho
AU - la Cour Freiesleben, Nina
AU - Zedeler, Anne
AU - Bungum, Mona
AU - Cardona, Alexia
AU - Perry, John R.B.
AU - Skouby, Sven O.
AU - Hoffmann, Eva R.
AU - Kelsey, Gavin
AU - Grøndahl, Marie Louise
PY - 2021
Y1 - 2021
N2 - Objective: To investigate whether epigenetic profiles of mural granulosa cells (MGC) and leukocytes from women with diminished ovarian reserve (DOR) differ from those of women with normal or high ovarian reserve. Design: Prospectively collected material from a multicenter cohort of women undergoing fertility treatment. Setting: Private and university-based facilities for clinical services and research. Patient(s): One hundred and nineteen women of various ages and ovarian reserve status (antimüllerian hormone level) who provided blood samples and MGC. Intervention(s): None. Main Outcome Measure(s): Measures of epigenetic aging rates from whole-genome methylation array data: DNA methylation variability, age acceleration, DNA methylation telomere length estimator (DNAmTL), and accumulation of epimutations. Result(s): Comparison of DOR or high ovarian reserve samples to controls (normal ovarian reserve) showed differential methylation variability between DOR and normal samples at 4,199 CpGs in MGC, and 447 between high and normal (false-discovery rate < 0.05). Variable sites in MGC from DOR were enriched in regions marked with the repressive histone modification H3K27me3, and also included genes involved in folliculogenesis, such as insulin growth factor 2 (IGF2) and antimüllerian hormone (AMH). Regardless of ovarian reserve, very few signals were detected in leukocytes, and no overlaps with those in MGC were found. Furthermore, we found a higher number of epimutations in MGC from women with DOR (Kruskal-Wallis test, difference in mean = 3,485). Conclusion(s): The somatic cells of human ovarian follicles have a distinctive epigenetic profile in women with DOR. A high frequency of epimutations suggests premature aging. Ovarian reserve status was not reflected in the leukocyte epigenetic profile.
AB - Objective: To investigate whether epigenetic profiles of mural granulosa cells (MGC) and leukocytes from women with diminished ovarian reserve (DOR) differ from those of women with normal or high ovarian reserve. Design: Prospectively collected material from a multicenter cohort of women undergoing fertility treatment. Setting: Private and university-based facilities for clinical services and research. Patient(s): One hundred and nineteen women of various ages and ovarian reserve status (antimüllerian hormone level) who provided blood samples and MGC. Intervention(s): None. Main Outcome Measure(s): Measures of epigenetic aging rates from whole-genome methylation array data: DNA methylation variability, age acceleration, DNA methylation telomere length estimator (DNAmTL), and accumulation of epimutations. Result(s): Comparison of DOR or high ovarian reserve samples to controls (normal ovarian reserve) showed differential methylation variability between DOR and normal samples at 4,199 CpGs in MGC, and 447 between high and normal (false-discovery rate < 0.05). Variable sites in MGC from DOR were enriched in regions marked with the repressive histone modification H3K27me3, and also included genes involved in folliculogenesis, such as insulin growth factor 2 (IGF2) and antimüllerian hormone (AMH). Regardless of ovarian reserve, very few signals were detected in leukocytes, and no overlaps with those in MGC were found. Furthermore, we found a higher number of epimutations in MGC from women with DOR (Kruskal-Wallis test, difference in mean = 3,485). Conclusion(s): The somatic cells of human ovarian follicles have a distinctive epigenetic profile in women with DOR. A high frequency of epimutations suggests premature aging. Ovarian reserve status was not reflected in the leukocyte epigenetic profile.
KW - DNA methylation
KW - epigenetics
KW - granulosa cells
KW - ovarian reserve
KW - reproduction
U2 - 10.1016/j.fertnstert.2020.09.009
DO - 10.1016/j.fertnstert.2020.09.009
M3 - Journal article
C2 - 33272626
AN - SCOPUS:85097098317
VL - 115
SP - 732
EP - 741
JO - Sexuality, Reproduction and Menopause
JF - Sexuality, Reproduction and Menopause
SN - 1546-2501
IS - 3
ER -
ID: 253026637