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人类囊胚中线粒体拷贝数的相关变量:滋养外胚层活检能告诉我们什么?

Variables associated with mitochondrial copy number in human blastocysts: what can we learn from trophectoderm biopsies?

机构信息

IVI-RMA, Valencia University, Valencia, Spain; I-Genomix, Valencia, Spain; Fundación IVI, Valencia, Spain.

I-Genomix, Valencia, Spain.

出版信息

Fertil Steril. 2018 Jan;109(1):110-117. doi: 10.1016/j.fertnstert.2017.09.022.

DOI:10.1016/j.fertnstert.2017.09.022
PMID:29307391
Abstract

OBJECTIVE

To study the potential variables that affect the mitochondrial DNA (mtDNA) content of trophectoderm (TE) cells in blastocysts that have undergone TE biopsy.

DESIGN

Observational retrospective single-center analysis.

SETTING

University-affiliated private in vitro fertilization center.

PATIENT(S): A total of 465 consecutive preimplantation genetic screening (PGS) cycles of 402 women undergoing preimplantation genetic testing.

INTERVENTION(S): Trophectoderm biopsy performed on blastocysts of women undergoing preimplantation genetic testing-aneuploidy (PGT-A).

MAIN OUTCOME MEASURE(S): The mtDNA content in trophectoderm cells.

RESULT(S): We checked the possible influence of patient characteristics, ovarian stimulation variables, embryo morphology, and embryo culture conditions on mtDNA values. Of all the analyzed variables, some such as body mass index (BMI), serum progesterone (P4), aneuploidy, and trophectoderm quality had an effect on mtDNA content in blastocysts. Body mass index had a small but positive effect on the mtDNA copy number; as the BMI values increased, the probability of women producing blastocysts with an mtDNA content above the median increased by 6%. For P4 serum concentration, an increase in P4 lowered the probability of blastocysts having values above the median by 39%. Embryo-associated variables such as TE quality and aneuploidy status appeared to affect the mtDNA copy number. For the aneuploid blastocysts, the probability of being above the median increased by 42%. Finally, blastocysts with poor quality TE had more chances of carrying higher mtDNA values.

CONCLUSION(S): Summarizing, larger quantities of mtDNA in blastocysts are associated with the condition of aneuploidy and low quality TE, as well as being from women with high BMI values. Understanding the biological meaning of mtDNA content in human blastocysts and what factors may interfere with their values is fundamental. Other key gaps, such as whether a correlation exists between mtDNA content and mitochondrial mass and biogenesis in human TE cells, and whether this correlation can be extended to the inner cell mass, need to be further addressed. These questions are currently being investigated.

摘要

目的

研究在进行滋养外胚层(TE)活检的囊胚中,影响线粒体 DNA(mtDNA)含量的潜在变量。

设计

观察性回顾性单中心分析。

设置

大学附属私立体外受精中心。

患者

共 465 个连续的植入前遗传学筛查(PGS)周期,涉及 402 名接受植入前遗传检测-非整倍体(PGT-A)的女性。

干预

对接受植入前遗传检测-非整倍体(PGT-A)的女性的囊胚进行滋养外胚层活检。

主要观察指标

滋养外胚层细胞中的 mtDNA 含量。

结果

我们检查了患者特征、卵巢刺激变量、胚胎形态和胚胎培养条件等可能对 mtDNA 值产生影响的因素。在所有分析的变量中,一些变量,如体重指数(BMI)、血清孕激素(P4)、非整倍体和滋养外胚层质量,对囊胚中的 mtDNA 含量有影响。BMI 对 mtDNA 拷贝数有微小但积极的影响;随着 BMI 值的增加,女性产生 mtDNA 含量高于中位数的囊胚的概率增加了 6%。对于 P4 血清浓度,P4 的增加降低了囊胚值高于中位数的概率 39%。胚胎相关变量,如 TE 质量和非整倍体状态,似乎影响 mtDNA 拷贝数。对于非整倍体囊胚,概率增加了 42%。最后,TE 质量差的囊胚更有可能携带更高的 mtDNA 值。

结论

综上所述,囊胚中 mtDNA 含量较多与非整倍体和 TE 质量差有关,也与 BMI 值较高的女性有关。了解人类囊胚中 mtDNA 含量的生物学意义以及哪些因素可能干扰其值是至关重要的。其他关键问题,如 mtDNA 含量与人类 TE 细胞中线粒体质量和生物发生之间是否存在相关性,以及这种相关性是否可以扩展到内细胞团,需要进一步解决。目前正在研究这些问题。

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