Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells

Chung, Tae‐Wook; Park, Mi-Ju; Kim, Hyung Sik; Choi, Hee‐Jung; Ha, Ki‐Tae

doi:10.1016/j.bbrc.2015.12.103

Cited by 40 publications

(19 citation statements)

References 22 publications

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“…The bulk of information on the role of integrins in enhancing endometrial receptivity has come from studies that investigated quantitative and qualitative status of integrins within endometrium of fertile and infertile women or women with recurrent miscarriages [ 12 ]. Also, a recent systematic review showed controversial data regarding endometrial αvβ3 integrin expression in patients with increased incidence of implantation failure [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

AlphaVBeta3 Integrin expression within uterine endometrium in unexplained infertility: a prospective cohort study

et al. 2017

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BackgroundImplantation defect is one of these contributing factors for unexplained infertility. In the mid-luteal phase, when implantation is expected to happen, Integrins expression is remarkably increased. So, Integrins could potentially serve as markers for the frame of the window of implantation. αVβ3 integrin could have a role as a potential receptor for embryonic attachment. The aim of the current study is to investigate whether the women with unexplained infertility have a pattern of expression of endometrial αvβ3 integrin that could differ from those who have normal fertility or not.MethodTwo groups of women have been included in this study. The first group was the Unexplained Infertility Group. This group included women diagnosed with unexplained primary infertility. The second group was the fertile Group, which included fertile parous women presented to the family planning clinic seeking contraception. 2D transvaginal ultrasound scan (TVS) was performed six days after detecting urinary LH surge. (TVS) was used to measure endometrial thickness, and subendometrial blood flow color Doppler Resistance Index (RI). On the same day of transvaginal ultrasound, endometrial samples were taken using the Endocell® office suction sampler for Immunohistochemistry (IHC) study using monoclonal mouse IgG antibodies to detect endometrial αvβ3 integrin.ResultsThirty-five fertile women with a diagnosis of unexplained infertility were included as a group I [Unexplained infertility Group] along with an equal number of fertile women as group II [Fertile Group]. The group of women with a diagnosis of unexplained infertility had a significantly lower αvβ3 integrin score when compared to the fertile group (median score 0, range:0–2 and median score 1, range: 1–3 and for infertile and fertile groups respectively, P < 0.0001). In addition, the unexplained infertility group had significantly higher subendometrial flow RI and Significantly thinner endometrial thickness.ConclusionThis study showed that Alpha v Beta 3 integrin is a significantly lower in endometrium in cases of unexplained infertility, which may suggest that underexpression of Alpha v Beta 3 integrin in human endometrium could be linked to defective uterine receptivity, and play a role as an unrecognized cause of infertility in this population of women. We need larger studies of adequate statistical power, ideally investigating more than one menstrual cycle in the same woman, to investigate the usefulness of using these molecular molecules in clinical practice.

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Section: Discussionmentioning

confidence: 99%

AlphaVBeta3 Integrin expression within uterine endometrium in unexplained infertility: a prospective cohort study

et al. 2017

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“…The expression of integrin βIII was found to be promoted by the embryonic interleukin (IL)-1 system, supporting the presence of cross-talk between blastocysts and the endometrial epithelium during embryonic implantation [41]. Recently, integrin αVβ3 and αVβ5 were reported to be necessary for the leukemia inhibitory factor-mediated adhesion of trophoblast cells to endometrial cells [36], whereas cell-surface CD44-hyaluronate binding was proposed to be employed by embryos during initial docking to endometrial epithelial cells [40]. This molecule is also involved in trophoblast invasion [42].…”

Section: Adhesion-promoting and -Inhibiting Moleculesmentioning

confidence: 91%

“…For human embryo implantation, several adhesion-promoting molecules, such as trophinin [27][28][29], L-selectin ligand [30][31][32][33], integrin αVβIII [34][35][36][37], and CD44 [38][39][40], were demonstrated to be expressed on human endometrial epithelial cells during the receptive phase. The expression of integrin βIII was found to be promoted by the embryonic interleukin (IL)-1 system, supporting the presence of cross-talk between blastocysts and the endometrial epithelium during embryonic implantation [41].…”

Section: Adhesion-promoting and -Inhibiting Moleculesmentioning

confidence: 99%

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Fujiwara

Ono

Sato

et al. 2020

IJMS

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Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely accepted that maternal–embryo communications, including embryonic signals, improve the receptive ability of the sex steroid hormone-primed endometrium. The embryo may utilize repulsive forces produced by an Eph–ephrin system for its timely attachment to and subsequent invasion through the endometrial epithelial layer. Importantly, the embryonic signals are considered to act on maternal immune cells to induce immune tolerance. They also elicit local inflammation that promotes endometrial differentiation and maternal tissue remodeling during embryo implantation and placentation. Additional clarification of the immune control mechanisms by embryonic signals, such as human chorionic gonadotropin, pre-implantation factor, zona pellucida degradation products, and laeverin, will aid in the further development of immunotherapy to minimize implantation failure in the future.

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“…From our recent study, the expression of integrin αVβ3 and αVβ5 induced by LIF treatment are required for endometrial receptivity [44]. However, the pattern of integrin expression in AN3CA is very similar to receptive endometrial cells, such as HEC-1A and Ishikawa [45].…”

Section: Discussionmentioning

confidence: 92%

Expression of ST6GalNAc1 and sialyl-Tn antigen enhances endometrial receptivity

Choi¹,

Chung²,

Kim³

et al. 2020

Preprint

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BackgroundTo characterize molecular mechanism underlying the regulation of sialylated glycan expression and its roles for endometrial receptivity and embryo implantation. Here, we characterized the role of a truncated form of sialylated O-glycan, sialyl-Tn, for endometrial receptivity. MethodsThe transcriptomes of human endometrium at mid-secretory phase were analyzed by Bioinformatics.Changes in gene expression, protein, and signal pathway were measured using RT-PCR and Western blot. The cell adhesion assay was visualized using a fluorescent microscope. In peri-implantation phase of mice, the expression of leukemia inhibitory factor (LIF) and sialyl-Tn were confirmed using immunohistochemistry and immnofluorescence analysis. The effect of sialy-Tn expression on embryo implantation was estimated by in vitro fertilization and embryo transfer using mice. ResultsIn in silico analysis, expression of O-glycosylation genes, especially ST6GalNAc1, was significantly increased in the human uterus of mid-secretory phase. Overexpression of the ST6GalNAc1 gene in non-receptive human endometrial AN3CA cells enhances the attachment of trophoblastic JAr cells. In an animal study, the results clearly indicated that sialyl-Tn was expressed on the surface of the midsecretory uterus. In addition, blockade of the receptor using free sialyl-Tn epitope diminished the implantation rates of intrauterine transferred murine embryos. ConclusionFrom these results, here we suggest that sialyl-Tn expression might be a novel factor regulating the endometrial receptivity for successful embryo implantation. BackgroundEmbryo implantation, a key process for a successful pregnancy, is one of the remaining unmet needs to improve the success rate of assisted reproduction [1]. The endometrium is receptive to embryo only during the implantation window, a short period of time about 6-10 days after ovulation [1,2]. A large number of molecular mediators including adhesive proteins, hormones, cytokines, and growth Authors' contributions HJC and TWC designed the experiments and performed the major molecular experiment. JK and JHJ performed in vitro fertilization and embryo transfer. BSK and MJP assisted the molecular experiments. KJK perfoermed the immunohistochemistry and immunoflurescent staining. JKJ and CHK analyzed the

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Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells

Cited by 40 publications

References 22 publications

AlphaVBeta3 Integrin expression within uterine endometrium in unexplained infertility: a prospective cohort study

AlphaVBeta3 Integrin expression within uterine endometrium in unexplained infertility: a prospective cohort study

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

Expression of ST6GalNAc1 and sialyl-Tn antigen enhances endometrial receptivity

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