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：辅助生殖的线索


背景技术单卵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。单绒毛膜同卵双胞胎共享一个绒毛膜，起源于单个囊胚内细胞团 (ICM) 的分裂。在双绒毛膜同卵双胞胎的经典模型中，胚胎在压缩之前分裂，发育成两个囊胚。然而，越来越多的 ART 病例中，单次囊胚移植导致双绒毛膜同卵双胞胎，这表明即使在囊胚形成后也可能发生胚胎分裂。目的和基本原理对于单绒毛膜同卵双胞胎，我们根据 ART 病例和动物实验，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同卵双胞胎的经典早期分裂模型。我们探索了 ART 中导致两个囊胚分离的细胞机制，这可能导致双绒毛膜同卵双胞胎。检索方法 在 PubMed 数据库中检索相关研究，包括研究文章、评论和会议论文。来自 IVF 诊所的同卵双胞胎病例是通过使用“同卵双胞胎”与“IVF 病例报告”、“ART”、“单胚胎移植”或“双绒毛膜”等术语的组合来发现的。检索到的论文根据所涉及的机制或无法解释的机制进行分类。通过“小鼠胚胎同卵双胞胎”、“小鼠8字孵化”、“斑马鱼janus突变体”、“九带犰狳胚胎”以及通过日常阅读收集的文献，发现了与同卵双胞胎相关的动物实验。检索仅限于英文文章，不限制发表日期或种类。 结果 对于单绒毛膜同卵双胞胎，ART 病例和小鼠实验证明，囊胚中较松的 ICM 会增加 ICM 分离的机会。囊胚腔形成或 8 形孵化所促进的物理力施加在 ICM 上，产生单绒毛膜同卵双胞胎。对于双绒毛膜同卵双胞胎，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、防止重新结合以及适当聚集，从而在生理情况下形成两个独立的人类囊胚。相比之下，涉及非典型孵化或玻璃化加热周期后单个囊胚移植的 ART 程序可能会导致囊胚分离。同卵双胞胎不同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这一研究领域的发展。正如未来方向中所讨论的，人类胚胎创新体外模型的最新发展可能会为人类胚胎发生过程中同卵双胞胎的细胞机制提供基本的新见解提供有希望的途径。更广泛的影响 双胎妊娠对胎儿和母亲都构成很高的风险。虽然单胚胎移植通常用于预防 ART 中的异卵双胞胎妊娠，但它不能预防同卵双胞胎的发生。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，以及对遗传机制的深入了解，可以改进 ART 手术期间的预测、预防甚至干预策略。注册号 不适用。