Project description:Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNAs (miRNA) have been implicated in several reproductive processes, the specific role of Dicer and miRNA in uterine development is not known. To address the roles of miRNA in the regulation of these key uterine pathways, we generated a conditional knockout (cKO) of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor (PR)-Cre. These Dicer cKO are sterile with small uteri, which demonstrate significant defects including absence of glandular epithelium and enhanced stromal apoptosis, beginning at postnatal day 15 with expression of Cre and deletion of Dicer. Although these mice had normal serum steroid hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/Beta-catenin canonical pathway, were dysregulated at the mRNA level. Gene expression profiling data from pools of Dicer cKO and control uteri groups, at 15 days. two group comparison
Project description:Transcription profiling by array of pancreatic tissues from wild-type mice, Mist1 knockout mice and Mist1 knockout mice with induced (rescued) MIST1 expression
Project description:Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.
Project description:Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNAs (miRNA) have been implicated in several reproductive processes, the specific role of Dicer and miRNA in uterine development is not known. To address the roles of miRNA in the regulation of these key uterine pathways, we generated a conditional knockout (cKO) of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor (PR)-Cre. These Dicer cKO are sterile with small uteri, which demonstrate significant defects including absence of glandular epithelium and enhanced stromal apoptosis, beginning at postnatal day 15 with expression of Cre and deletion of Dicer. Although these mice had normal serum steroid hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/Beta-catenin canonical pathway, were dysregulated at the mRNA level.