Ablation of the miR-465 Cluster Causes a Skewed Sex Ratio in Mice.
Ablation of the miR-465 Cluster Causes a Skewed Sex Ratio in Mice.
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DOI：
10.3389/fendo.2022.893854
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
X连锁的miR-465簇在睾丸、精子、新生卵巢和囊胚以及8-16细胞胚胎中高度表达。然而，miR-465簇的生理作用在很大程度上仍不清楚。本研究旨在剖析miR-465簇在小鼠发育中的作用。尽管miR-465miRNA簇在睾丸中大量表达，但使用CRISPR-Cas9切除miR-465miRNA簇并未导致不育。相反，在miR-465 KO小鼠中观察到了偏向雄性的性别比(60%的雄性)。进一步的分析表明，雌性胚胎早在胚胎8.5天(E8.5)就选择性地退化。小RNA深度测序、qPCR和原位杂交分析表明，miR-465簇编码的miRNAs主要定位于胚外组织/发育中的胎盘。RNA-seq分析发现，在E7.5的KO胚胎中，以许多关键的胎盘基因，如Alkbh1，的调控异常为特征的改变的mRNA转录组。综上所述，这项研究表明miR-465簇是正常女性胎盘发育所必需的，并且由于女性胚胎的选择性退化和吸收，miR-465簇的消融导致了性别比的扭曲，更多的男性(~60%)。
The X-linked miR-465 cluster is highly expressed in the testis, sperm, newborn ovary, and blastocysts as well as in 8-16 cell embryos. However, the physiological role of the miR-465 cluster is still largely unknown. This study aims to dissect the role of the miR-465 cluster in murine development. Despite abundant expression in the testis, ablation of the miR-465 miRNA cluster using CRISPR-Cas9 did not cause infertility. Instead, a skewed sex ratio biased toward males (60% males) was observed among miR-465 KO mice. Further analyses revealed that the female conceptuses selectively degenerated as early as embryonic day 8.5 (E8.5). Small RNA deep sequencing, qPCR, and in situ hybridization analyses revealed that the miRNAs encoded by the miR-465 cluster were mainly localized to the extraembryonic tissue/developing placenta. RNA-seq analyses identified altered mRNA transcriptome characterized by the dysregulation of numerous critical placental genes, e.g., Alkbh1, in the KO conceptuses at E7.5. Taken together, this study showed that the miR-465 cluster is required for normal female placental development, and ablation of the miR-465 cluster leads to a skewed sex ratio with more males (~60%) due to selective degeneration and resorption of the female conceptuses.
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影响因子：
46.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1038/nrc3932
发表时间：
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期刊：
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影响因子：
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通讯作者：
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作者：
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影响因子：
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