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通过血液中 DNA 甲基化水平测量表观遗传时钟的年龄加速与卵母细胞产量减少有关。

Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

机构信息

Department of Obstetrics & Gynecology, Thomas Jefferson University Hospital, 833 Chestnut Street, Suite 301, Philadelphia, PA, 19107, USA.

Department of Reproductive Endocrinology & Infertility, Stanford Hospital and Clinics, Stanford, CA, USA.

出版信息

J Assist Reprod Genet. 2020 May;37(5):1097-1103. doi: 10.1007/s10815-020-01763-0. Epub 2020 Apr 13.

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.

摘要

目的

研究生物年龄(身体机能表现的年龄)大于实际年龄(年龄加速(AgeAccel))与卵子产量的相关性。

方法

本研究纳入了 39 名接受卵巢刺激的女性,包括所有不孕诊断。利用外周血甲基化分析来确定生物年龄。将生物年龄比实际年龄大 2 岁以上定义为年龄加速。采用负二项式模型获得年龄加速与卵子数量的粗关联。采用向后选择法(p<0.05)获得卵子数量的简约调整模型。

结果

年龄指标与卵子数量呈负相关(实际年龄 Pearson ρ=-0.45,生物年龄 Pearson ρ=-0.46),而 AMH 与卵子数量呈正相关(Pearson ρ=0.91)。年龄加速患者的 AMH 值较低(分别为 1.29ng/mL 和 2.29ng/mL(p=0.049)),卵子产量也较低(分别为 5.50 个和 14.50 个(p=0.0030))。在年龄加速组中发现卵子数量减少 7 个的粗关联(-6.9 个卵子(CI-11.6,-2.4))。在包含 AMH 和窦卵泡计数的模型中,年龄加速与卵子数量减少 3.3 个具有统计学意义(-3.1;95%CI-6.5,-0.1;p=0.036)。

结论

在这项小型初步研究中,年龄加速与 AMH 降低和卵子产量降低相关,这初步证明生物年龄,特别是年龄加速,可以作为一种表观遗传生物标志物,提高预测模型评估卵巢储备的能力。

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