Heparin-binding epidermal growth factor (HB-EGF) may improve embryonic development and implantation by increasing vitronectin receptor (integrin ανβ3) expression in peri-implantation mouse embryos

Lim, Jinho; Lee, Dong Ryul; Song, Haengseok; Kim, Kye-Seong; Yoon, Tae Ki; Gye, Myung Chan; Kim, Moon Kyoo

doi:10.1007/s10815-006-9021-9

Cited by 28 publications

(28 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HBEGF signaling is required to increase HBEGF protein levels when O 2 is decreased to 2% [18], and both immunohistochemical and ELISA data indicated that HBEGF upregulation can be mediated by any one of the three MAPK pathways. These data confirm prior reports that HBEGF inhibits apoptosis [18,19,24,43] and promotes differentiation of trophoblast cells toward a migratory, extravillous phenotype [15,17,44]. Moreover, the new findings identify separate downstream signaling pathways mediated by HBEGF-induced ERBB/HER activation that are responsible for each functional outcome.…”

Section: Discussionsupporting

confidence: 89%

Function-Specific Intracellular Signaling Pathways Downstream of Heparin-Binding EGF-Like Growth Factor Utilized by Human Trophoblasts1

Jessmon

Kilburn

Romero

et al. 2010

Biology of Reproduction

View full text Add to dashboard Cite

Heparin-binding EGF-like growth factor (HBEGF) is expressed by trophoblast cells throughout gestation. First-trimester cytotrophoblast cells are protected from hypoxia-induced apoptosis because of the accumulation of HBEGF through a posttranscriptional autocrine mechanism. Exogenous application of HBEGF is cytoprotective in a hypoxia/reoxygenation (H/R) injury model and initiates trophoblast extravillous differentiation to an invasive phenotype. The downstream signaling pathways induced by HBEGF that mediate these various cellular activities were identified using two human first-trimester cytotrophoblast cell lines, HTR-8/SVneo and SW.71, with similar results. Recombinant HBEGF (1 nM) induced transient phosphorylation of MAPK3/1 (ERK), MAPK14 (p38), and AKT within 15 min and JNK after 1-2 h. To determine which downstream pathways regulate the various functions of HBEGF, cells were treated with specific inhibitors of the ERK upstream regulator MEK (U0126), the AKT upstream regulator phosphoinositide-3 (PI3)-kinase (LY294002), MAPK14 (SB203580), and JNK (SP600125), as well as with inactive structural analogues. Only SB203580 specifically prevented HBEGF-mediated rescue during H/R, while each inhibitor attenuated HBEGF-stimulated cell migration. Accumulation of HBEGF at reduced oxygen was blocked only by a combination of U0126, SB203580, and SP600125. We conclude that HBEGF advances trophoblast extravillous differentiation through coordinate activation of PI3 kinase, ERK, MAPK14, and JNK, while only MAPK14 is required for its antiapoptotic activity. Additionally, hypoxia induces an autocrine increase in HBEGF protein levels through MAPK14, JNK or ERK. These experiments reveal a complexity of the intracellular signaling circuitry that regulates trophoblast functions critical for implantation and placentation.

show abstract

Section: Discussionsupporting

confidence: 89%

Function-Specific Intracellular Signaling Pathways Downstream of Heparin-Binding EGF-Like Growth Factor Utilized by Human Trophoblasts1

Jessmon

Kilburn

Romero

et al. 2010

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…EGF (Desai et al 2000) and HB-EGF (Martin et al 1998;Lim et al 2006) have also been reported to stimulate the proportion of hatching blastocysts in several mammalian species. The mechanisms by which growth factors promote the formation of hatching blastocysts are not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…Culture media supplemented with various growth factors have been used to study their possible effect on in vitro development. A number of studies have reported that for in vitro culture of preimplantation embryos, the addition of exogenous growth factors, including the epidermal growth factor (EGF) family, the insulin and insulin-like family of growth factors, the transforming growth factor-β (TGF-β) family, the platelet-derived growth factor and fibroblast growth factor family, could affect the preimplantation development and result in a broad range of effects that include stimulation of protein synthesis in mice (Wood and Kaye 1989) and pigs (Lewis et al 1992), promotion of blastocyst formation in cattle (Larson et al 1992;Yang et al 1993;Lima et al 2006) and mice (Paria and Dey 1990), increasing the percentage of hatching blastocysts in mice (Lim et al 2006) and humans (Martin et al 1998), increase in the number cells in blastocysts in mice (Lin et al 2003) and cattle (Sirisathien et al 2003), and prevention of apoptosis in rabbits (Herrler et al 1998) and human (Spanos et al 2000).Clearly a better understanding of the role of growth factors in development could help to elucidate the mechanisms controlling embryonic development and to improve the viability and development of embryos in vitro.…”

Section: Introductionmentioning

confidence: 99%

Effect of nerve growth factor (NGF) on the development of preimplantation rabbit embryos in vitro

Pei

2009

Vet Res Commun

View full text Add to dashboard Cite

This study aimed to investigate the effect of nerve growth factor (NGF) on the development of preimplantation rabbit embryos in vitro. Zygotes were collected from superovulated New Zealand rabbits 19 h after injection of hCG and immediately mating and cultured in TCM-199 plus fatty-acid free BSA with different concentrations of NGF. Zygotes not treated with NGF served as control. At 24 h, 48 h, 72 h and 96 h of the culture, the numbers of the early cleavage stage, morulae, blastocysts and hatching blastocysts were determined. The intrazonal diameter of the blastocyst and the total cell numbers per blastocyst were measured after 96 h of culture. The results showed: (1) NGF at 100 ng/mL and 1000 ng/mL could improve the numbers of the hatching blastocysts which developed compared to the control treatment (p < 0.05); (2) All concentrations of NGF increased the total cell numbers in the blastocysts compared to the control treatment (p < 0.05); (3) NGF had no significant effect on the blastocyst intrazonal diameter of the blastocysts at 96 h of culture (p = 0.493); (4) The proportion in the early cleavage stage at 24 h of culture (p = 0.635), of morulae at 48 h of culture (p = 0.812) and of blastocysts at 72 h of culture (p = 0.812) in all treatments were not significantly different.

show abstract

“…Over the past decades, it has been well established that endometrial integrins are hormonedependent (Lessey, 1995) and participate in multiple reproductive events including fertilization, implantation and placentation in various species (Bowen and Hunt, 2000). Some factors known to be involved in the implantation process, such as IGF-1 (Kabir-Salmani et al, 2004), CCN1 (Winterhager and Gellhaus, 2014) and HB-EGF (Lim et al, 2006), may act through interaction with integrins. Of the integrin members, the αVβ3 Figure 3 (A) Relative luciferase activity in HEK293T cells co-transfected with miR-126a-3p mimics, inhibitor and the wide-type (wt-) or mutant (mu-) Itga11 vectors.…”

Section: Article In Pressmentioning

confidence: 99%

Mmu-miR-126a-3p plays a role in murine embryo implantation by regulating Itga11

Jia

Gou

et al. 2015

Reproductive BioMedicine Online

View full text Add to dashboard Cite

miR-126a-3p has been found to be specifically up-regulated in the process of murine embryo implantation. This study aimed to further clarify the role of miR-126a-3p in embryo implantation. The expression of miR-126a-3p in implantation sites was significantly higher than that in interimplantation sites (P = 0.009). Its expression dynamics in a series of models, including pseudopregnancy, delayed implantation and artificial decidualization, suggested that the induction of miR-126a-3p is dependent on hormonal signalling and decidualization of the endometrium. Bioinformatic analysis predicted and luciferase activity assay confirmed that Itga11, a member of the integrin family, was a target gene of miR-126a-3p. miR-126a-3p bound to the 3' untranslated region of Itga11 and regulated Itga11 by inhibiting mRNA translation and affecting mRNA stability. Transwell assay showed that miR-126a-3p promoted cell migratory and invasive capacity in vitro. Loss of function of miR-126a-3p significantly reduced the number of implantation sites in vivo (P = 0.013). Collectively, miR-126a-3p may play a major role in embryo implantation by regulating Itga11, possibly through impairing cell migratory and invasive capacity. These findings should contribute to a better understanding of the miRNA-based mechanism of embryo implantation.

show abstract

Heparin-binding epidermal growth factor (HB-EGF) may improve embryonic development and implantation by increasing vitronectin receptor (integrin ανβ3) expression in peri-implantation mouse embryos

Abstract: HB-EGF may improve implantation by accelerating expression of integrin alphanubeta3 in peri-implantation mouse embryos.

Cited by 28 publications

References 22 publications

Function-Specific Intracellular Signaling Pathways Downstream of Heparin-Binding EGF-Like Growth Factor Utilized by Human Trophoblasts1

Function-Specific Intracellular Signaling Pathways Downstream of Heparin-Binding EGF-Like Growth Factor Utilized by Human Trophoblasts1

Effect of nerve growth factor (NGF) on the development of preimplantation rabbit embryos in vitro

Mmu-miR-126a-3p plays a role in murine embryo implantation by regulating Itga11

Contact Info

Product

Resources

About