OBJECTIVES The female reproductive tract comprises several different cell types. Using three representative Cre systems, we comparatively analysed the phenotypes of Dgcr8 conditional knockout (cKO) mice to understand the function of Dgcr8, involved in canonical microRNA biogenesis, in the female reproductive tract. MATERIALS AND METHODS Dgcr8f/f mice were crossed with Ltficre/+ , Amhr2cre/+ or PRcre/+ mice to produce mice deficient in Dgcr8 in epithelial (Dgcr8ed/ed ), mesenchymal (Dgcr8md/md ) and all the compartments (Dgcr8td/td ) in the female reproductive tract. Reproductive phenotypes were evaluated in Dgcr8 cKO mice. Uteri and/or oviducts were used for small RNA-seq, mRNA-seq, real-time RT-PCR, and/or morphologic and histological analyses. RESULT Dgcr8ed/ed mice did not exhibit any distinct defects, whereas Dgcr8md/md mice showed sub-fertility and oviductal smooth muscle deformities. Dgcr8td/td mice were infertile due to anovulation and acute inflammation in the female reproductive tract and suffered from an atrophic uterus with myometrial defects. The microRNAs and mRNAs related to immune modulation and/or smooth muscle growth were systemically altered in the Dgcr8td/td uterus. Expression profiles of dysregulated microRNAs and mRNAs in the Dgcr8td/td uterus were different from those in other genotypes in a Cre-dependent manner. CONCLUSIONS Dgcr8 deficiency with different Cre systems induces overlapping but distinct phenotypes as well as the profiles of microRNAs and their target mRNAs in the female reproductive tract, suggesting the importance of selecting the appropriate Cre driver to investigate the genes of interest.

中文翻译：

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不同的 Cre 系统在 Dgcr8 条件敲除小鼠的雌性生殖道中诱导不同的 microRNA 景观和异常

目的 女性生殖道包括几种不同的细胞类型。我们使用三个代表性的 Cre 系统，比较分析了 Dgcr8 条件敲除 (cKO) 小鼠的表型，以了解 Dgcr8 在雌性生殖道中参与规范 microRNA 生物发生的功能。材料和方法将 Dgcr8f/f 小鼠与 Ltficre/+、Amhr2cre/+ 或 PRcre/+ 小鼠杂交以产生上皮 (Dgcr8ed/ed)、间充质 (Dgcr8md/md) 和所有隔室 (Dgcr8td/d) 中 Dgcr8 缺陷的小鼠) 在女性生殖道中。在 Dgcr8 cKO 小鼠中评估了生殖表型。子宫和/或输卵管用于小 RNA-seq、mRNA-seq、实时 RT-PCR 和/或形态学和组织学分析。结果 Dgcr8ed/ed 小鼠没有表现出任何明显的缺陷，而 Dgcr8md/md 小鼠表现出低生育力和输卵管平滑肌畸形。Dgcr8td/td 小鼠由于无排卵和雌性生殖道急性炎症而不能生育，并且患有子宫萎缩并伴有子宫肌层缺陷。与免疫调节和/或平滑肌生长相关的 microRNA 和 mRNA 在 Dgcr8td/td 子宫中发生了系统性改变。Dgcr8td/td 子宫中失调的 microRNA 和 mRNA 的表达谱以 Cre 依赖性方式与其他基因型中的表达谱不同。结论 具有不同 Cre 系统的 Dgcr8 缺陷会诱导女性生殖道中重叠但不同的表型以及 microRNA 及其靶标 mRNA 的谱，这表明选择合适的 Cre 驱动程序来研究感兴趣的基因的重要性。