Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation

Hirota, Yasushi

doi:10.1507/endocrj.ej18-0431

Cited by 42 publications

(31 citation statements)

References 43 publications

(108 reference statements)

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“…Subsequently, we focused on the role of M2 M s in the endometrium during implantation. Elevated P4 concentrations after ovulation dramatically change the state of endometrial cell proliferation and render the uterus receptive to the embryo as a normal uterine morphological change that occurs during pre-implantation (26). In normal conditions, luminal epithelial cells are known to cease proliferation for implantation (26,27); however, in M2(-) mice, the number of Ki-67-positive endometrial epithelial cells was higher compared to the control at the preimplantation period (E3.5), suggesting that the endometrial epithelial cells did not undergo the required change for receiving the embryo (Figure 5).…”

Section: Figure 7 | Expression Of Tnfα Inos Cd11cmentioning

confidence: 99%

CD206+ M2-Like Macrophages Are Essential for Successful Implantation

et al. 2020

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Section: Figure 7 | Expression Of Tnfα Inos Cd11cmentioning

confidence: 99%

CD206+ M2-Like Macrophages Are Essential for Successful Implantation

et al. 2020

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“…To elucidate why Stat3-eKO and Stat3-sKO females exhibit implantation failure, we examined the mRNA expression of genes regulated by 17β-estradiol (E 2 ) and progesterone (P 4 ). Former investigations have clarified that appropriate balance between E 2 and P 4 signaling is a crucial factor for uterine receptivity [1][2][3][4]25,27,28 . Therefore, we performed quantitative PCR and examined the expression of Muc1, C3, and Ltf as E 2 -responsive genes in the epithelium, Indian hedgehog (Ihh) and Hoxa10 as P 4 -responsive genes in the epithelium and stroma on day 4 of pregnancy.…”

Section: Stromal Stat3 Suppresses Excessive Estrogenic Responses In Tmentioning

confidence: 99%

“…Stromal STAT3 suppresses cell proliferation in the luminal epithelium and epithelial STAT3 forms slit-like structure of uterine lumen in the peri-implantation uterus. In the peri-implantation mouse uterus, the luminal epithelial cells undergo cessation of proliferation and the stromal cells have increased proliferative activity, as we call "proliferation-differentiation switching (PDS)" in embryo implantation 1,3,4,6 . PDS is mainly influenced by the balance of E 2 and P 4 signaling and is thought to be a critical determinant for uterine receptivity 4,14,27,29 .…”

Section: Stromal Stat3 Suppresses Excessive Estrogenic Responses In Tmentioning

confidence: 99%

Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment

Hiraoka

Hirota

Fukui

et al. 2020

Sci Rep

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Although it has been reported that uterine signal transducer and activator of transcription 3 (STAT3) is essential for embryo implantation, the exact roles of uterine epithelial and stromal STAT3 on embryo implantation have not been elucidated. To address this issue, we generated Stat3-floxed/Ltf-iCre (Stat3-eKO), Stat3-floxed/Amhr2-Cre (Stat3-sKO), and Stat3-floxed/Pgr-Cre (Stat3-uKO) mice to delete Stat3 in uterine epithelium, uterine stroma, and whole uterine layers, respectively. We found that both epithelial and stromal STAT3 have critical roles in embryo attachment because all the Stat3-eKO and Stat3-sKO female mice were infertile due to implantation failure without any embryo attachment sites. Stat3-eKO uteri showed indented structure of uterine lumen, indicating the role of epithelial STAT3 in slit-like lumen formation in the peri-implantation uterus. Stat3-sKO uteri exhibited hyper-estrogenic responses and persistent cell proliferation of the epithelium in the peri-implantation uterus, suggesting the role of stromal STAT3 in uterine receptivity. In addition, Stat3-uKO female mice possessed not only the characteristic of persistent epithelial proliferation but also that of indented structure of uterine lumen. These findings indicate that epithelial STAT3 controls the formation of slit-like structure in uterine lumen and stromal STAT3 suppresses epithelial estrogenic responses and cell proliferation. Thus, epithelial and stromal STAT3 cooperatively controls uterine receptivity and embryo attachment through their different pathways.

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“…It progresses through specific stages in response to ovarian hormones. The receptive mouse uterus displays stromal proliferation and epithelial differentiation as an indicator of proper arrangement for blastocyst implantation [17] , which is governed by ovarian hormones. In another word, increased production of ovarian hormones E 2 and P 4 provides the uterus with a capacity of blastocyst attachment pre-decidualization.…”

Section: Discussionmentioning

confidence: 99%

TJCYR ameliorates embryo implantation dysfunction through PI3K/Akt/eNOS signalling to improve endometrial receptivity

Huang

Lei

Xia

et al. 2020

Preprint

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Backgroud: In our clinical practice, we found that Tiao Jing Cu Yun Recipe (TJCYR), which was composed of Dangshen, Danshen, Danggui, Huangqi, Shudihuang, Bajitian and Yinyanghuo, had obviously enhanced the rate of pregnancy in the women with infertility. Although the application effects are desirable and satisfactory, the therapeutic mechanism of TJCYR remains poorly understood. In this study, we evaluated the effect of TJCYR on embryo implantation dysfunction (EID)-induced damage of endometrial receptivity in mice and investigated the mechanisms underlying the effect. Methods: Pregnant mice were randomly divided into six groups: Control, EID only, Progesterone (Prog)+EID, TJCYR-low-dose+EID , TJCYR-medium-dose+EID, TJCYR-high-dose+EID. Mifepristone was injected to make EID model. On the eighth day of pregnancy, the mice were sacrificed and the number of uterus-implanted blastocysts was counted. On the fourth day of pregnancy, the serum was to analyze the level of hormone by radioimmunoassay, the uterus was to analyze morphology by H&E and SEM, the combination of immunofluorescence and western blot were to identify the related proteins. Results: Compared with the EID group, the mice treated with high-dose TJCYR had a greater number of implanted sites, so we choose that dose of TJCYR as treatment in the following study. The mice treatment with TJCYR could significantly enhance the level of P 4 , and inhibite the decrease in the expression of PR that induced by EID. Compared with the EID only, the SEM showed that a marked increase in the number of well-developed pinopodes in the TJCYR treatment group. Except morphological marker, several molecules in relation to pinopodes that could be used as biomarkers. TJCYR abrogated the EID-induced weakened in those biomarkers. Additionally, the vascular density and VEGF were decreased in the EID group, it appeared severe tissue hypoxia, while TJCYR reversed that change. Compared with the control, the p-Akt and p-eNOS were decreased in EID group, accompanied with decline of NO. While TJCYR promoted the activation of Akt and eNOS, to improve the poor microvascular environment of endometrium. Conclusion: TJCYR has therapeutic potential against poor endometrial receptivity via activation of the PI3K/AKT/eNOS signaling pathway.

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Progesterone governs endometrial proliferation-differentiation switching and blastocyst implantation

Cited by 42 publications

References 43 publications

CD206+ M2-Like Macrophages Are Essential for Successful Implantation

CD206+ M2-Like Macrophages Are Essential for Successful Implantation

Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment

TJCYR ameliorates embryo implantation dysfunction through PI3K/Akt/eNOS signalling to improve endometrial receptivity

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