Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice
Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice
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囊胚孵化的部位特异性显着影响小鼠的妊娠结局
DOI：
10.1096/fj.202100653r
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发表时间：
2021-09-01
期刊：
影响因子：
4.8
通讯作者：
Du, Fuliang
中科院分区：
文献类型：
--
作者：
An, Liyou;Liu, Yanhong;Du, Fuliang
胚泡从透明膜（ZP）孵化，使植入子宫内膜上皮，但很少有人知道孵化部位对妊娠结局的影响。根据内细胞团中心对应的起始滋养外胚层投射（TEP）/ZP位置，将小鼠孵化胚胎分为5组。在体外培养12小时后的囊胚（3.5 dpc）中，A位（44.4%）和B位（38.6%）胚胎的TEP率高于C位（12.5%）和D位（3.1%）胚胎，而O位（1.4%）最低（P <0.05）。ET后A部位（55.6%）和B部位（65.6%）的出生率高于C部位胚胎（21.3%）和对照组（P <0.05）。此外，当两种胚胎移植到相同的受体时，B位点胚胎的活产率仍然高于C位点胚胎（68.8% vs 31.3%; P <0.05）。不同的TEP位点囊胚表现出不同的植入能力：ET后2天，C位点胚胎的植入率低于A和B位点组（分别为67.7% vs 84.3%和83.2%; P <0.05）。C位点胚胎的发育缺陷率（47.5%）也明显高于A位点和B位点胚胎（分别为22.5%和14.6%），植入失败主要与出生率低相关，这一发现得到了差异基因表达分析（如LIF、LIFR和S100 a9）的证实。令人惊讶的是，酸化台氏液（AAH）处理的B部位囊胚（77.1%）的出生率显著高于C部位囊胚（55.3%）和对照囊胚（43.4%）。位点特异性和胚胎孵化过程中的差异基因表达可用于ART筛选。更重要的是，AAH辅助孵化对于改善妊娠和足月发育是有效和可行的，特别是在B-部位，对于人类和畜牧业。
Blastocysts hatch from the zona pellucida (ZP) to enable implantation into the uterine endometrial epithelium, but little is known regarding the effect of hatching sites on pregnancy outcomes. Murine hatching embryos were categorized into five groups based on initial trophectoderm projection (TEP)/ZP position corresponding to the inner cell mass center. In blastocysts (3.5 dpc) post‐12 hours in vitro culture, TEP rates of A‐site (44.4%) and B‐site (38.6%) embryos were higher than those of C‐site (12.5%) and D‐site (3.1%) embryos, while the O‐site (1.4%) was the lowest (P < .05). Post‐ET A‐site (55.6%) and B‐site (65.6%) birth rates were higher than those of C‐site embryos (21.3%) and controls (P < .05). Furthermore, live birth rate of B‐site embryos remained higher than C‐site embryos (68.8% vs 31.3%; P < .05) when both were transferred into the same recipients. Different TEP site blastocysts exhibited different implantation competences: the implantation rate of C‐site embryos was lower than that of both A‐ and B‐site groups (67.7% vs 84.3% and 83.2%, respectively; P < .05) at 2 days post‐ET. C‐site embryos also had a distinctly higher ratio of developmental defects (47.5%) than A‐ and B‐site embryos (22.5% and 14.6%, respectively), with implantation failure mainly associated with poor birth rate, a finding corroborated by differential gene expression analysis such as LIF, LIFR, and S100a9. Surprisingly, acidified Tyrode's solution (AAH)‐treated B‐site blastocysts had a significantly increased birth rate (77.1%) than C‐site (55.3%) and controls (43.4%). Site specificity and differential gene expression during embryo hatching can be applied in ART screening. More importantly, assisted hatching by AAH is effective and feasible for improving pregnancy and term development, particularly at the B‐site, for humans and in animal husbandry.