无创胚胎植入前遗传学检查研究进展

doi:10.11843/j.issn.0366-6964.2025.11.003

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (11): 5367-5378.doi: 10.11843/j.issn.0366-6964.2025.11.003

无创胚胎植入前遗传学检查研究进展

宋浩然¹^,²(), 冯肖艺¹, 张笑梦¹, 杨柏高¹, 李崇阳¹, 董建华¹, 刘阳¹^,², 王子卓¹^,², 王昆³, 崔凯², 赵学明¹^,*()

1. 中国农业科学院北京畜牧兽医研究所, 北京 100193
2. 青岛农业大学动物科技学院, 青岛 266000
3. 河北省农林科学院粮油作物研究所河北省作物栽培生理与绿色生产重点实验室, 石家庄 050035

收稿日期:2025-03-31 出版日期:2025-11-23 发布日期:2025-11-27
通讯作者: 赵学明 E-mail:1315503802@qq.com;zhaoxueming@caas.cn
作者简介:宋浩然(2001-)，男，山东泰安人，硕士生，主要从事动物繁殖研究，E-mail: 1315503802@qq.com
基金资助:
国家重点研发计划政府间重点专项(2022YFE0100200)；农业农村部和财政部资助：现代农业产业技术体系资助(CARS-36)；国家家养动物种质资源库；国家自然科学基金国际合作项目(32161143032)；中国农业科学院科技创新工程(ASTIP-IAS06)

Research Progress of Noninvasive Preimplantation Genetic Examination

SONG Haoran¹^,²(), FENG Xiaoyi¹, ZHANG Xiaomeng¹, YANG Baigao¹, LI Chongyang¹, DONG Jianhua¹, LIU Yang¹^,², WANG Zizhuo¹^,², WANG Kun³, CUI Kai², ZHAO Xueming¹^,*()

1. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
2. College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266000, China
3. Key Laboratory of Crop Cultivation Physiology and Green Production in Heibei Province, Institute of Cereal and Oil Crops, Hebei Academy of Agriculture and Forestry Science, Shijiazhuang 050035, China

Received:2025-03-31 Online:2025-11-23 Published:2025-11-27
Contact: ZHAO Xueming E-mail:1315503802@qq.com;zhaoxueming@caas.cn

摘要/Abstract

摘要：

胚胎植入前基因检查(preimplantation genetic testing，PGT)不仅在人类生殖医学上发挥着重要作用，还在畜牧业上有重要的应用。家畜良种繁育过程中，PGT可用于引入理想性状，增强遗传多样性，提高整体畜群质量。通过选择具有特定遗传特征的胚胎，可以提高诸如抗病性、生产力和寿命等性状，促进畜牧育种计划进步。基于基因组评估的胚胎选择通过增加选择强度，缩短世代间隔，从而增加遗传增益。然而，当前PGT主要采用有创检查，这会对胚胎结构完整性造成破坏。因此，最大程度地保存胚胎结构完整性能够更好地维持其活力，目前已开始探究采用无创检查(ni-PGT)来评估胚胎植入前的发育潜能，包括检测囊胚液和胚胎培养基中无细胞DNA(cell-free DNA，cfDNA)。本文概述了PGT和无创胚胎进行PGT方法，整理了现有PGT在畜牧业及人类辅助生殖方面的应用进展，以期为ni-PGT在畜牧领域广泛应用提供理论参考。

关键词: 胚胎植入前基因检查(PGT), 囊胚液检查, 胚胎培养基检查, 胚胎

Abstract:

Preimplantation genetic testing (PGT) not only plays a significant role in human reproductive medicine but also has important applications in animal husbandry. In the process of breeding superior livestock, PGT can be used to introduce desirable traits, enhance genetic diversity, and improve the overall quality of the herd. By selecting embryos with specific genetic characteristics, traits such as disease resistance, productivity, and lifespan can be enhanced, thus promoting progress in animal breeding programs. Embryo selection based on genomic evaluation increases selection intensity and shortens generation intervals, thereby increasing genetic gain. However, current PGT mainly employs invasive methods, which can damage the structural integrity of embryos. Therefore, preserving the structural integrity of embryos to the greatest extent can better maintain their viability. Currently, non-invasive PGT (ni-PGT) methods are being explored to assess the developmental potential of embryos before implantation, including the detection of cell-free DNA (cfDNA) in blastocoel fluid and embryo culture medium. This article summarizes the methods of PGT and non-invasive PGT for embryos, and compiles the application progress of existing PGT in animal husbandry and human assisted reproduction, with the aim of providing theoretical references for the wide application of ni-PGT in the field of animal husbandry.

Key words: preimplantation genetic testing(PGT), blastocyst fluid testing, embryo medium testing, embryo

中图分类号:

S814.8

宋浩然, 冯肖艺, 张笑梦, 杨柏高, 李崇阳, 董建华, 刘阳, 王子卓, 王昆, 崔凯, 赵学明. 无创胚胎植入前遗传学检查研究进展[J]. 畜牧兽医学报, 2025, 56(11): 5367-5378.

SONG Haoran, FENG Xiaoyi, ZHANG Xiaomeng, YANG Baigao, LI Chongyang, DONG Jianhua, LIU Yang, WANG Zizhuo, WANG Kun, CUI Kai, ZHAO Xueming. Research Progress of Noninvasive Preimplantation Genetic Examination[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(11): 5367-5378.

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名称 Name	检查内容 Scope of test	检查意义 Significance of test	参考文献 Reference
PGT-A	识别染色体数目正常的胚胎	选择整倍体胚胎，具有提高妊娠率、降低流产率、缩短妊娠所需时间等临床益处	[21-26]
PGT-M	识别致病性核DNA变异导致单基因疾病	避免将致病性核DNA变异导致单基因疾病传递给后代	[27-29]
PGT-SR	检查染色体是否发生结构重排	选择无致病性结构重排的胚胎，以改善妊娠情况	[30-32]

名称 Name	技术应用 Technology application	优点 Advantage	参考文献 Reference
WGA	对样本中全部基因组序列进行非选择性的、均匀性扩增的技术	提高了可用于后续检测的遗传数据的数量和质量	[33-34]
SNP	检查基因组DNA序列中由于某个核苷酸突变引起的多态性	SNP分析能提供完整的数据信息和具有极高的分辨率，可用于优良畜种的筛选	[35, 40-42]
NGS	单次生化反应中同时检测几十万至数百万DNA模板上碱基序列的DNA测序技术	高通量测序技术，边合成边测序，检测效率高，应用范围广	[43-44]
aCGH	一种基于微阵列的技术，将待测DNA与正常对照DNA样本进行杂交比较，以检测出待测样本重复或缺失的区域	能够在整个基因组范围内检测出染色体异常, 包括染色体非整倍体、缺失和重复	[48-49]
RT-qPCR	在PCR体系中加入特定荧光染料或探针，扩增过程中通过荧光信号累积对PCR进程进行实时检测的技术	可以实时监控反应产物，提供准确的定量，消除了反应后凝胶分析的需要	[50-51]

胚胎数量及类型 Number and type of embryos	采样时期 Sampling period	采样内容及体积 Sampling content and volume	扩增方法及成功率 Amplification method and success rate	检测内容及一致性 Testing content and consistency	参考文献 Reference
116新鲜人类胚胎 116 fresh human embryos	D5	0.01 μL 囊胚液	SurePlex (82%，95/116)	PGT-A BF vs. TE(97.1%，67/69)	[56]
				PGT-A BF vs. BM(94.4%，34/36)
				PGT-A BF vs. PB(94.1%，32/34)
16冷冻人类胚胎 16 frozen human embryos	D5	0.01 μL 囊胚液	PicoPlex (62.5%，10/16)	PGT-A BF vs. TE(40%，4/10)	[57]
96冷冻人类胚胎 96 frozen human embryos	D5	1 μL 囊胚液	SurePlex (63%，60/96)	PGT-A BF vs. TE(40%，29/60)	[58]
23新鲜人类胚胎 23 fresh human embryos	D5	约0.01 μL 囊胚液	SurePlex (34.8%，8/23)	PGT-A BF vs. TE(37.5%，3/8)	[59]

胚胎数量及类型 Number and type of embryos	采样时期 Sampling period	采样内容及体积 Sampling content and volume	扩增方法及成功率 Amplification method and success rate	检测内容及一致性 Testing content and consistency	参考文献 Reference
53冷冻人类胚胎 53 frozen human embryos	D5/D6	SCM+BF	MALBAC (88%，46/52)	D5，PGT-A SCM+BF vs. WEs(45%，5/11)	[62]
53冷冻人类胚胎 53 frozen human embryos	D5/D6	SCM+BF	MALBAC (88%，46/52)	D6，PGT-A SCM+BF vs. WE(66%，23/35)	[62]
62冷冻人类胚胎 62 frozen human embryos	D5/D6	SCM+BF 10 μL	MALBAC (100%，62/62)	PGT-A SCM+BF vs. TE(90.48%，19/21) SCM+BF vs. WE(85.71%，18/21)	[63]
62冷冻人类胚胎 62 frozen human embryos	D5/D6	SCM+BF 10 μL	MALBAC (100%，62/62)	PGT-SR SCM+BF vs. TE(90.24%，37/41) SCM+BF vs. WE(100%，41/41)	[63]
145新鲜人类胚胎 145 fresh human embryos	D5/D6	SCM+BF 5 μL	SurePlex (93%，40/43)	PGT-A SCM+BF vs. TE(97.4%，37/38)	[64]
19新鲜人类胚胎 19 fresh human embryos	D5/D6	SCM+BF	SurePlex (100%，19/19)	PGT-A SCM+BF vs. TE(100%，19/19)	[65]

胚胎数量及类型 Number and type of embryos	采样时期 Sampling period	采样内容及体积 Sampling content and volume	扩增方法及成功率 Amplification method and success rate	检测内容及一致性 Testing content and consistency	参考文献 Reference
28新鲜人类胚胎 28 fresh human embryos	D5/D6	SCM 2.5 μL	SurePlex (92.86%，26/28)	PGT-A SCM vs. TE(50%，13/26)	[72]
28冷冻人类胚胎 28 frozen human embryos	D5/D6	SCM	SurePlex (100%，28/28)	PGT-A SCM vs. WE(96.4%，27/28)	[65]
28冷冻人类胚胎 28 frozen human embryos	D5/D6	SCM	SurePlex (100%，28/28)	PGT-A SCM vs. TE(87.5%，21/24)	[65]
60新鲜人类胚胎 60 fresh human embryos	D6	SCM	SurePlex (91.67%，55/60)	PGT-A SCM vs. TE(94.5%，52/55)	[52]
56冷冻人类胚胎 56 frozen human embryos	D5	SCM	MALBAC (100%，56/56)	PGT-A SCM vs. WE(94.64%，53/56)	[69]
52冷冻人类胚胎 52 frozen human embryos	D5/D6	SCM 10 μL	MALBAC (92.3%，48/52)	PGT-A SCM vs. WE(93.8%，45/48)	[70]
26新鲜、9冷冻人类胚胎 26 fresh, 9 frozen human embryos	D5/D6	SCM 15 μL	PicoPlex (74.3%，26/35)	PGT-A SCM vs. ICM(58.33%，14/24)	[73]
1 301新鲜人类胚胎 1 301 fresh human embryos	D5/D6	SCM 10 μL	ReproSeq PGS Kit (92%，1 197/1 301)	PGT-A SCM vs. TE(78.2%，886/1108)	[71]
20冷冻人类胚胎 20 frozen human embryos	D6	SCM	SurePlex (95%，19/20)	PGT-A SCM vs. TE(55.6%，10/18)	[74]
27新鲜人类胚胎 27 fresh human embryos	D5/D6	SCM 25 μL	NICs inst (96.3%，26/27)	PGT-A SCM vs. TE(69.2%，18/26)	[25]

无创胚胎植入前遗传学检查研究进展

Research Progress of Noninvasive Preimplantation Genetic Examination

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