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 AND RATIONALE 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. SEARCH 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. OUTCOMES 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. WIDER IMPLICATIONS 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. REGISTRAITON NUMBER N/A.

中文翻译：

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同卵双胞胎的细胞机制：来自辅助生殖的线索


背景 同卵 （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。共享一个绒毛膜的单绒毛膜 MZ 双胞胎起源于单个囊胚内细胞团 （ICM） 的分裂。在双绒毛膜 MZ 双胞胎的经典模型中，胚胎在压缩前分裂，发育成两个囊胚。然而，越来越多的 ART 病例中单个囊胚移植导致双绒毛膜 MZ 双胞胎，这表明即使在囊胚形成后也可能发生胚胎分裂。目标和基本原理 对于单绒毛膜 MZ 双胞胎，我们从 ART 病例和动物实验中对 ICM 分裂所涉及的细胞机制进行了全面分析。此外，我们批判性地重新审视了双绒毛膜 MZ 双胞胎的经典早期分裂模型。我们探讨了在 ART 中导致两个分离的囊胚的细胞机制，这可能导致双绒毛膜 MZ 双胞胎。检索方法 在 PubMed 数据库中检索了包括研究文章、评论和会议论文在内的相关研究。通过使用包括“同卵双胞胎”与“IVF 病例报告”、“ART”、“单胚胎移植”或“二绒毛膜”在内的术语组合来发现来自 IVF 诊所的 MZ 双胞胎病例。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。使用“小鼠胚胎单卵双胞胎”、“小鼠 8 形孵化”、“斑马鱼 janus 突变体”和“九带犰狳胚胎”以及通过日常阅读收集的文献发现了与 MZ 双胞胎相关的动物实验。检索仅限于英文文章，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，囊胚中较松散的 ICM 会增加 ICM 分离的机会。囊胚腔形成或 8 形孵化促进的物理力施加在 ICM 上，导致单绒毛膜 MZ 双胞胎。对于双绒毛膜 MZ 双胞胎，经典模型类似于小鼠胚胎的体外人工克隆，需要严格控制分裂力、防止重新结合和适当聚集，这允许在生理条件下形成两个独立的人类囊胚。相比之下，涉及在非典型孵化或玻璃化加热循环后转移单个囊胚的 ART 程序可能会导致囊胚分离。MZ 双胞胎的各种动物模型系统在形态、分子机制和时间上的差异可能会阻碍该研究领域。正如未来方向所讨论的那样，人类胚胎创新体外模型的最新发展可能为人类胚胎发生过程中 MZ 双胞胎的细胞机制提供有前途的新见解。更广泛的影响 双胞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防止 ART 中的异卵双胞胎妊娠，但它无法防止 MZ 双胞胎的发生。利用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，可以在 ART 手术过程中改进预测、预防甚至干预策略。注册号 N/A。