Effect of ulipristal acetate and mifepristone at emergency contraception dose on the embryo-endometrial attachment using an in vitro human trophoblastic spheroid and endometrial cell co-culture model

Li, Raymond; Li, Ying-Xing; Li, Tiantian; Fan, Hongjie; Ng, Ernest Hung-Yu; Yeung, William S.B.; Ho, Pak‐Chung; Lee, Ckf

doi:10.1093/humrep/dex328

Cited by 33 publications

(9 citation statements)

References 24 publications

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“…Then, how does AIF-1 affect endometrial receptivity? In further experiment, we cocultured Ishikawa cells as the endometrial surrogate and JAR cells as the embryo surrogate to simulate the embryo implantation process in vitro (Li et al, 2017) and found that highly expressed AIF-1 could inhibit the adhesion of JAR cells to Ishikawa cells significantly. Adhesion is well known as an important step in trophoblast invasion.…”

Section: Discussionmentioning

confidence: 99%

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol

Zhou

Wang

et al. 2018

Human Reproduction

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This work was supported by grants from the National Natural Science Foundation of China, Grant numbers 81771656 and 81370763; Clinical research special fund of Chinese Medical Association, Grant number 16020480664; Shanghai Jiao Tong University Medicine-Engineering Fund, Grant number YG2017ZD11 and YG2017MS57; and the Merck-Serono China Research Fund for Fertility Agreement. P.C.K.L. is supported by a Canadian Institutes of Health Research Foundation Scheme Grant 143317. None of the authors has any competing interests.

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Section: Discussionmentioning

confidence: 99%

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol

Zhou

Wang

et al. 2018

Human Reproduction

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“…Ishikawa (Human endometrial epithelial cells), Jeg-3 (HTB-36), and AN3 CA (Human endometrial epithelial cells) cells were purchased from American Type Culture Collection (ATCC, USA). The embryo attachment in vitro model was constructed as described previously with minor modifications 24 . Briefly, Ishikawa and Jeg-3 were cultured in DMEM/F-12 medium containing 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

Liang

Luo

et al. 2019

Cell Death Dis

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Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

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“…4 Bc and Cc), as compared to the vector-transfected and non-transfected control cells. However, in-vitro experimental studies using trophoblastic spheroids made from JAR cells line as the embryo surrogate ( Evron et al , 2011 ; Zhang et al , 2011 ; Li et al , 2017 ) found that up-regulation of AQP3 had no effect on JAR cells adhesion to HEC-1A cells (Fig. 4 Bd and Ce).…”

Section: Resultsmentioning

confidence: 97%

Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial epithelial cells

et al. 2018

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STUDY QUESTIONHow does aquaporin-3 (AQP3) affect endometrial receptivity?SUMMARY ANSWERAQP3, which is regulated by the combination and estrogen (E2) and progesterone (P4), induces epithelial–mesenchymal transition (EMT) of endometrial epithelial cells.WHAT IS KNOWN ALREADYEmbryo implantation is an extremely complex process, and endometrial receptivity is essential for successful embryo implantation. Estrogen and progesterone regulate endometrial receptivity. AQP3, which is regulated by estrogen (E2), increases cell migration and invasion ability by regulating the expression of EMT-related factors and influencing the reorganization of the actin cytoskeleton.STUDY DESIGN, SIZE, DURATIONThis study investigated the pathophysiological significance of AQP3 in human endometrial function during different phases of the menstrual cycle.PARTICIPANTS/MATERIALS, SETTING, METHODSAQP3 expression levels during different phases of the menstrual cycle were measured using immunohistochemical assays. In cells of different receptivity (high-receptive RL95-2 cells and low-receptive HEC-1A cells), the expression of AQP3 was measured using western blotting, qRT-PCR and immunofluorescence assays. Activities of AQP3, and its regulation by E2 and P4, were studied through in-vitro experiments using RL95-2 cells.MAIN RESULTS AND THE ROLE OF CHANCEAQP3 expression in the mid- and late-secretory phases of the human endometrium is significantly higher than in other phases. Since AQP3 expression levels were higher in RL95-2 cells than in HEC-1A cells, mechanisms of AQP3 regulation by E2 and P4 were studied using RL95-2 cells. We provided the first report that P4 up-regulates AQP3 by directly targeting the promoter of the AQP3 gene. The up-regulation of AQP3 expression by a combination of E2 and P4 is significantly higher than that caused by either E2 or P4 alone. Together E2 and P4 promote RL95-2 cell migration and invasion by inducing EMT through AQP3. We also found that AQP3 co-localizes with ezrin and affects the formation of filopodia and lamellipodia during the E2 and P4-induced EMT process but has no effect on the expression of ezrin and F-actin.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONIt is still unclear whether AQP3 is a main regulator of endometrial receptivity or one of several factors influencing the process.WIDER IMPLICATIONS OF THE FINDINGSFurther investigation on AQP3 may contribute to a greater understanding of endometrial receptivity.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the National Natural Scientific Grants of China (No. 31570798), the Program for Liaoning Excellent Talents in University (LR2017042), the Doctoral Scientific Research Foundation of Liaoning province (201601236), and the Liaoning Provincial Program for Top Discipline of Basic Medical Sciences. There are no conflicts of interest.

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Effect of ulipristal acetate and mifepristone at emergency contraception dose on the embryo-endometrial attachment using an in vitro human trophoblastic spheroid and endometrial cell co-culture model

Abstract: We had free supply of the UPA compound used in this study from Laboratoire HRA Pharma. This work was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, The University of Hong Kong, Hong Kong.

Cited by 33 publications

References 24 publications

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol

Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial epithelial cells

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