母体在植入前阶段暴露于高压氧可通过Nrf2-Notch1上调和Nf2下调增加小鼠胚泡中的细胞凋亡和异位Cdx2表达,并降低Oct4表达。

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY Developmental Dynamics Pub Date : 2023-10-18 DOI:10.1002/dvdy.671
Yu-Ming Li, Yu Lang Chung, Yung-Fu Wu, Chien-Kuo Wang, Chieh-Min Chen, Yi-Hui Chen
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引用次数: 0

摘要

背景:据报道,在人类和小鼠胚胎发生过程中,环境氧张力会影响胚泡质量和内部细胞团(ICM)中的细胞数量。虽然在低氧条件下导致ICM细胞数量和多能性基因表达增加的分子机制已经被破译,目前尚不清楚是哪些调节途径导致母体暴露于高压氧(HBO)后胎儿体重不足和胎盘超重。结果:暴露于HBO的妊娠小鼠的胚泡显示活性氧(ROS)和核Nrf2染色信号显著增加,Nf2和Oct4表达降低,增加细胞核Tp53bp1和活性胱天蛋白酶3染色,以及ICM中Cdx2、Yap和Notch1细胞内结构域(N1ICD)的异位核信号。在暴露于HBO的胚泡的ICM中,Nf2 cDNA微注射和Nrf2 shRNA微注射均显著降低了Cdx2、Tp53bp1和Yap的异位核表达,而增加了Oct4的表达,而Nrf2-shRNA微注射也显著降低了Notch1mRNA水平以及N1ICD和活性胱天蛋白酶3的核表达。结论:我们首次表明,母体在植入前暴露于HBO通过上调Nrf2-Notch1-Cdx2表达和下调Nf2-Oct4表达来诱导细胞凋亡并损害ICM细胞的特异性。
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Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation

Background

The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO).

Results

The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3.

Conclusion

We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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