Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yiel
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REPRODUCTIVE PHYSIOLOGY AND DISEASE
Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield Brent Monseur 1 & Gayathree Murugappan 2 & Jason Bentley 3 & Nelson Teng 4 & Lynn Westphal 2 Received: 16 December 2019 / Accepted: 27 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. Methods Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05). Results Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = − 0.45, biologic age Pearson ρ = − 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (− 6.9 oocytes (CI − 11.6, − 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (− 3.1; 95% CI − 6.5, − 0.1; p = 0.036). Conclusions In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve. Keywords Epigenetics . DNA methylation . Ovarian aging . Infertility . Aging . Methylome . Epigenetic clock
Introduction All organisms experience physiologic changes with time; however, discrepancies in the rate and risk associated with This manuscript has not been published and is not under consideration for publication elsewhere. * Brent Monseur [email protected] 1
Department of Obstetrics & Gynecology, Thomas Jefferson University Hospital, 833 Chestnut Street, Suite 301, Philadelphia, PA 19107, USA
2
Department of Reproductive Endocrinology & Infertility, Stanford Hospital and Clinics, Stanford, CA, USA
3
Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA
4
Department of Gynecologic Oncology, Stanford Hospital and Clinics, Stanford, CA, USA
senescence are not captured by chronologic age alone and are affected by both genetic and non-genetic factors [1, 2]. A recent review detailed the cellular and molecular hallmarks of aging including genomic ins
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