背景:单卵(MZ)双胞胎被认为是由单个受精胚胎在不同阶段的裂变产生的。单拓扑MZ双胞胎,分享一个绒毛膜,起源于单个胚泡内的内细胞团(ICM)的分裂。在经典的双色子MZ双胞胎模型中,胚胎在压实前分裂,发育成两个胚泡.然而,有越来越多的ART病例,其中单个胚泡转移导致多胎MZ双胞胎,表明即使在胚泡形成后也可能发生胚胎分裂。
目标:对于单绒毛膜MZ双胞胎,我们对ICM分裂的细胞机制进行了全面分析,从ART病例和动物实验中提取。此外,我们批判性地重新研究了双色子MZ双胞胎的经典早期分裂模型。我们探索在ART中导致两个分离胚泡的细胞机制,可能导致双色子MZ双胞胎。
方法:相关研究,包括研究文章,reviews,在PubMed数据库中搜索了会议论文。通过使用术语组合发现IVF诊所的MZ双胞胎病例,包括“单卵双胞胎”和“IVF病例报告”,\'ART\',\'单胚胎移植\',或“二色子”。检索到的论文根据所涉及的机制或具有无法解释的机制进行分类。与MZ双胞胎相关的动物实验是使用“小鼠胚胎单卵双胞胎”发现的,\'鼠标8形阴影\',\'斑马鱼Janus突变体\',和“九带状的Armadillo胚胎”,以及通过日常阅读收集的文学作品。搜索仅限于英文文章,对出版日期或物种没有限制。
结果:对于单绒毛膜MZ双胞胎,ART病例和小鼠实验表明,胚泡中较松散的ICM会增加ICM分离的机会。由胚层形成或8形阴影促进的物理力施加在ICM上,导致单绒毛膜MZ双胞胎。对于二氧质MZ双胞胎,经典模型类似于体外人工克隆小鼠胚胎,需要严格控制分裂力,重新加入预防,和适当的聚合,这允许在生理情况下形成两个独立的人类胚泡。相比之下,涉及非典型孵化或玻璃化加热周期后单个胚泡转移的ART程序可能导致胚泡分离。形态差异,分子机制,MZ孪生的各种动物模型系统的时间安排可能会阻碍这一研究领域。正如在未来的方向上讨论的那样,人类胚胎创新体外模型的最新发展可能提供有希望的途径,为人类胚胎发生过程中MZ孪生的细胞机制提供基本的新见解。
结论:双胎妊娠对胎儿和母亲都构成高风险。虽然单胚胎移植通常用于预防ART中的双卵双胎妊娠,它不能防止MZ双胞胎的发生。根据我们对单绒毛膜和双绒毛膜MZ孪生的细胞机制的理解,以及对遗传机制的见解,可以实现改进的预测,预防,甚至在ART过程中的干预策略。
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BACKGROUND: Monozygotic (MZ) twins are believed to arise from the fission of a single fertilized embryo at different stages. Monochorionic MZ twins, who share one chorion, originate from the splitting of the inner cell mass (ICM) within a single blastocyst. In the classic model for dichorionic MZ twins, the embryo splits before compaction, developing into two blastocysts. However, there are a growing number of ART cases where a single blastocyst transfer results in dichorionic MZ twins, indicating that embryo splitting may occur even after blastocyst formation.
OBJECTIVE: For monochorionic MZ twins, we conducted a comprehensive analysis of the cellular mechanisms involved in ICM splitting, drawing from both ART cases and animal experiments. In addition, we critically re-examine the classic early splitting model for dichorionic MZ twins. We explore cellular mechanisms leading to two separated blastocysts in ART, potentially causing dichorionic MZ twins.
METHODS: Relevant studies including research articles, reviews, and conference papers were searched in the PubMed database. Cases of MZ twins from IVF clinics were found by using combinations of terms including \'monozygotic twins\' with \'IVF case report\', \'ART\', \'single embryo transfer\', or \'dichorionic\'. The papers retrieved were categorized based on the implicated mechanisms or as those with unexplained mechanisms. Animal experiments relating to MZ twins were found using \'mouse embryo monozygotic twins\', \'mouse 8-shaped hatching\', \'zebrafish janus mutant\', and \'nine-banded armadillo embryo\', along with literature collected through day-to-day reading. The search was limited to articles in English, with no restrictions on publication date or species.
RESULTS: For monochorionic MZ twins, ART cases and mouse experiments demonstrate evidence that a looser ICM in blastocysts has an increased chance of ICM separation. Physical forces facilitated by blastocoel formation or 8-shaped hatching are exerted on the ICM, resulting in monochorionic MZ twins. For dichorionic MZ twins, the classic model resembles artificial cloning of mouse embryos in vitro, requiring strictly controlled splitting forces, re-joining prevention, and proper aggregation, which allows the formation of two separate human blastocysts under physiological circumstances. In contrast, ART procedures involving the transfer of a single blastocysts after atypical hatching or vitrified-warmed cycles might lead to blastocyst separation. Differences in morphology, molecular mechanisms, and timing across various animal model systems for MZ twinning can impede this research field. As discussed in future directions, recent developments of innovative in vitro models of human embryos may offer promising avenues for providing fundamental novel insights into the cellular mechanisms of MZ twinning during human embryogenesis.
CONCLUSIONS: Twin pregnancies pose high risks to both the fetuses and the mother. While single embryo transfer is commonly employed to prevent dizygotic twin pregnancies in ART, it cannot prevent the occurrence of MZ twins. Drawing from our understanding of the cellular mechanisms underlying monochorionic and dichorionic MZ twinning, along with insights into the genetic mechanisms, could enable improved prediction, prevention, and even intervention strategies during ART procedures.
UNASSIGNED: N/A.