Identification of a unique epigenetic profile in women with diminished ovarian reserve

Article In Press

Like Comment
Related Content

Authors:

Kristina W. Olsen, M.Sc., Ph.D., Juan Castillo-Fernandez, Ph.D., Andrew Cho Chan, M.Sc., Nina la Cour Freiesleben, Ph.D., Anne Zedeler, Ph.D., Mona Bungum, Ph.D., Alexia Cardona, Ph.D., John R.B. Perry, Ph.D., Sven O. Skouby, D.M.Sc., Eva R. Hoffmann, Ph.D., Gavin Kelsey, Ph.D., Marie Louise Grøndahl, D.M.Sc.

Abstract:

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.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

No comments yet.