Identification of Gene Expression Changes Associated With Uterine Receptivity in Mice

He, Jia-Peng; Zhao, Miao; Zhang, Wenqian; Huang, Mingyu; Zhu, Can; Cheng, Hao-Zhuang; Liu, Ji‐Long

doi:10.3389/fphys.2019.00125

Cited by 18 publications

(8 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, several groups have reported comprehensive analyses of genes expressed in early pregnant uteri. 31 , 32 , 33 , 34 However, these studies only examined limited time points or compared whole endometria before or after implantation. In this paper, we focused on luminal epithelial cells that directly communicate with blastocysts.…”

Section: Discussionmentioning

confidence: 99%

A gene network of uterine luminal epithelium organizes mouse blastocyst implantation

Aikawa

Hirota

Fukui

et al. 2022

Reprod Medicine & Biology

View full text Add to dashboard Cite

Purpose The receptive endometrium is critical for blastocyst implantation. In mice, after blastocysts enter the uterine cavities on day 4 of pregnancy (day 1 = vaginal plug), blastocyst attachment is completed within 24 h, accompanied by dynamic interactions between the uterine luminal epithelium and the blastocysts. Any failures in this process compromise subsequent pregnancy outcomes. Here, we performed comprehensive analyses of gene expression at the luminal epithelium in the peri‐implantation period. Methods RNA‐seq combined with laser microdissection (LMD) was used to reveal unique gene expression kinetics in the epithelium. Results We found that the prereceptive epithelium on day 3 specifically expresses cell cycle‐related genes. In addition, days 3 and 4 epithelia express glutathione pathway‐related genes, which are protective against oxidative stresses. In contrast, day 5 epithelium expresses genes involved in glycolysis and the regulation of cell proliferation. The genes highly expressed on days 3 and 4 compared to day 5 are related to progesterone receptor signaling, and the genes highly expressed on day 5 compared to days 3 and 4 are associated with the ones regulated by H3K27me3. Conclusions These results suggest that specific gene expression patterns govern uterine functions during early pregnancy, contributing to implantation success.

show abstract

Section: Discussionmentioning

confidence: 99%

A gene network of uterine luminal epithelium organizes mouse blastocyst implantation

Aikawa

Hirota

Fukui

et al. 2022

Reprod Medicine & Biology

View full text Add to dashboard Cite

show abstract

“… 8 , 9 , 10 , 11 , 12 , 13 Previously, by using RNA‐seq, we determined global gene expression changes associated with uterine receptivity in mice. 14 We revealed 541 differentially expressed genes with 316 genes being up‐regulated and 225 genes being down‐regulated in the receptive uterus compared to the pre‐receptive uterus, presenting a useful candidate gene list for further study of uterine receptivity in mice. However, a clear limitation is that the whole uterus was used for RNA‐seq analysis.…”

Section: Introductionmentioning

confidence: 97%

“…By using gene knockout mice, a number of genes have been proved to play key roles in uterine receptivity 8‐13 . Previously, by using RNA‐seq, we determined global gene expression changes associated with uterine receptivity in mice 14 …”

Section: Introductionmentioning

confidence: 99%

Deciphering mouse uterine receptivity for embryo implantation at single‐cell resolution

2021

View full text Add to dashboard Cite

ObjectivesMice are widely used as an animal model for studying human uterine receptivity for embryo implantation. Although transcriptional changes related to mouse uterine receptivity have been determined by using bulk RNA‐seq, the data are of limited value because the uterus is a complex organ consisting of many cell types. Here, we aimed to decipher mouse uterine receptivity for embryo implantation at single‐cell resolution.Materials and methodsSingle‐cell RNA sequencing was performed for the pre‐receptive and the receptive mouse uterus. Gene expression profiles in luminal epithelium and glandular epithelium were validated by comparing against a published laser capture microdissection (LCM)‐coupled microarray dataset.ResultsWe revealed 19 distinct cell clusters, including 3 stromal cell clusters, 2 epithelial cell clusters, 1 smooth muscle cell cluster, 4 endothelial cell clusters and 8 immune cell clusters. We identified global gene expression changes associated with uterine receptivity in each cell type. Additionally, we predicted signalling interactions for distinct cell types to understand the crosstalk between the blastocyst and the receptive uterus.ConclusionOur data provide a valuable resource for deciphering the molecular mechanism underlying uterine receptivity in mice.

show abstract

“…Due to the difficulty in studying human endometrial receptivity in vivo , endometrial epithelial cells cultured in vitro from primary endometrial biopsies are a commonly utilised model 13 . Moreover, due to species differences, mouse models of receptivity are also limited in their usefulness due to differences in gene expression profiles required for mouse receptivity 24 . For these reasons, we use primary human endometrial epithelial cells cultured in vitro as a model of endometrial receptivity here.…”

Section: Introductionmentioning

confidence: 99%

miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity

Griffiths

Sinderen

Rainczuk

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The endometrium is a highly complex tissue that is vulnerable to subtle gene expression changes and is the first point of contact for an implanting blastocyst. Successful blastocyst implantation can only occur when the endometrium is receptive during a short window with each menstrual cycle. microRNAs are small, non-coding RNAs that negatively regulate their gene targets. miR-29c has previously been identified to be differentially regulated across the fertile menstrual cycle, however it has not been investigated in association with infertility. We hypothesised that miR-29c dysregulation in the infertile endometrium would negatively influence endometrial adhesion and blastocyst implantation outcomes during the mid-secretory, receptive phase. miR-29c expression was elevated in early and mid-secretory phase infertile endometrium and localised to the epithelial compartments of endometrial tissue. Overexpression of miR-29c in vitro impaired endometrial epithelial adhesion, and reduced collagen type IV alpha 1 (COL4A1) mRNA expression. COL4A1 was immunolocalised to the luminal and glandular epithelial basement membranes in early and mid-secretory phase fertile and infertile endometrium for the first time. Knockdown of COL4A1 impaired endometrial epithelial adhesion suggesting a role in endometrial receptivity and implantation. Our data suggests miR-29c overexpression with infertility may impair the adhesive capacity of the endometrium, potentially contributing to implantation failure and infertility.

show abstract

Identification of Gene Expression Changes Associated With Uterine Receptivity in Mice

Cited by 18 publications

References 80 publications

A gene network of uterine luminal epithelium organizes mouse blastocyst implantation

A gene network of uterine luminal epithelium organizes mouse blastocyst implantation

Deciphering mouse uterine receptivity for embryo implantation at single‐cell resolution

miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity

Contact Info

Product

Resources

About