Radiosensitive target in the mouse embryo chimera assay: Implications that the target involves autocrine growth factor function

Jeffrey M. Peters, Eleanor C. Tsark, Lynn M. Wiley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mouse preimplantation embryos express at least two functional cell surface growth factor receptors that are radiosensitive in other cell types, the epidermal growth factor receptor (EGF receptor) and the insulin-like growth factor I receptor (IGF-I receptor). These embryos also express ligands that bind to and activate these receptors, including transforming growth factor alpha (TGF-α) and insulin-like growth factor II (IGF-II), which bind to the EGF receptor and IGF-I receptor, respectively. Embryo-expressed IGF-II and TGF-α increase embryo cell number-a measure of proliferation rate- and stimulate blastocoele formation-a measure of cell differentiation-allowing the embryo to self-modulate cell proliferation and morphogenesis into a blastocyst (Paria and Dey, Proc. Natl. Acad. Sci. USA 87, 4756-4760, 1990; Dardik and Schultz, Development 113, 919-930, 1991: Rappolee et al., Genes Dev. 6, 939-952, 1992). In this work, we tested the hypothesis that IGF-I receptor and/or EGF receptor function may be impaired to produce the radiation-induced competitive cell proliferation disadvantage that is expressed by irradiated embryos that are aggregated with nonirradiated embryos in chimeras. Cleavage-stage embryos were irradiated with 137Cs γ rays (0.5 or 1.0 Gy) and paired with nonirradiated same-stage embryos to form groups of chimeras that were cultured in control medium or medium containing IGF-II, insulin, EGF or TGF-α. The cell proliferation disadvantage expressed by the irradiated embryos within chimeras was completely eliminated by IGF- II or insulin. In contrast to the rescue action of IGF-II or insulin in chimeras, neither EGF nor TGF-α could prevent the cell proliferation disadvantage exhibited by irradiated embryos paired with nonirradiated embryos in chimeras. For irradiated conventionally cultured zona-enclosed embryos, IGF-II and TGF-α did not increase mean embryo cell number significantly, although both IGF-II and TGF-α did increase blastocoele formation significantly. Collectively, these results support the following conclusions: (1) Ligands for the IGF-I receptor can rescue irradiated embryos from competitive cell proliferation disadvantage in chimeras, while ligands for the EGF receptor cannot; (2) IGF-I receptor function and EGF receptor function are affected differently by ionizing radiation with respect to competitive cell proliferation and are affected similarly by ionizing radiation with respect to blastocoele formation; (3) EGF receptor-dependent stimulation of competitive cell proliferation and cell differentiation are affected differently by ionizing radiation in preimplantation embryos.

Original languageEnglish (US)
Pages (from-to)722-729
Number of pages8
JournalRadiation research
Volume145
Issue number6
DOIs
StatePublished - Jun 6 1996

Fingerprint

embryos
mice
Intercellular Signaling Peptides and Proteins
Embryonic Structures
insulin
Insulin-Like Growth Factor II
Epidermal Growth Factor Receptor
IGF Type 1 Receptor
Transforming Growth Factor alpha
Cell Proliferation
Blastocyst
Ionizing Radiation
Insulin
Ligands
Epidermal Growth Factor
Cell Differentiation
ionizing radiation
Cell Count
cells
Growth Factor Receptors

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

@article{7ed78fb6bb6b47929abab4270c4344da,
title = "Radiosensitive target in the mouse embryo chimera assay: Implications that the target involves autocrine growth factor function",
abstract = "Mouse preimplantation embryos express at least two functional cell surface growth factor receptors that are radiosensitive in other cell types, the epidermal growth factor receptor (EGF receptor) and the insulin-like growth factor I receptor (IGF-I receptor). These embryos also express ligands that bind to and activate these receptors, including transforming growth factor alpha (TGF-α) and insulin-like growth factor II (IGF-II), which bind to the EGF receptor and IGF-I receptor, respectively. Embryo-expressed IGF-II and TGF-α increase embryo cell number-a measure of proliferation rate- and stimulate blastocoele formation-a measure of cell differentiation-allowing the embryo to self-modulate cell proliferation and morphogenesis into a blastocyst (Paria and Dey, Proc. Natl. Acad. Sci. USA 87, 4756-4760, 1990; Dardik and Schultz, Development 113, 919-930, 1991: Rappolee et al., Genes Dev. 6, 939-952, 1992). In this work, we tested the hypothesis that IGF-I receptor and/or EGF receptor function may be impaired to produce the radiation-induced competitive cell proliferation disadvantage that is expressed by irradiated embryos that are aggregated with nonirradiated embryos in chimeras. Cleavage-stage embryos were irradiated with 137Cs γ rays (0.5 or 1.0 Gy) and paired with nonirradiated same-stage embryos to form groups of chimeras that were cultured in control medium or medium containing IGF-II, insulin, EGF or TGF-α. The cell proliferation disadvantage expressed by the irradiated embryos within chimeras was completely eliminated by IGF- II or insulin. In contrast to the rescue action of IGF-II or insulin in chimeras, neither EGF nor TGF-α could prevent the cell proliferation disadvantage exhibited by irradiated embryos paired with nonirradiated embryos in chimeras. For irradiated conventionally cultured zona-enclosed embryos, IGF-II and TGF-α did not increase mean embryo cell number significantly, although both IGF-II and TGF-α did increase blastocoele formation significantly. Collectively, these results support the following conclusions: (1) Ligands for the IGF-I receptor can rescue irradiated embryos from competitive cell proliferation disadvantage in chimeras, while ligands for the EGF receptor cannot; (2) IGF-I receptor function and EGF receptor function are affected differently by ionizing radiation with respect to competitive cell proliferation and are affected similarly by ionizing radiation with respect to blastocoele formation; (3) EGF receptor-dependent stimulation of competitive cell proliferation and cell differentiation are affected differently by ionizing radiation in preimplantation embryos.",
author = "Peters, {Jeffrey M.} and Tsark, {Eleanor C.} and Wiley, {Lynn M.}",
year = "1996",
month = "6",
day = "6",
doi = "10.2307/3579363",
language = "English (US)",
volume = "145",
pages = "722--729",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "6",

}

Radiosensitive target in the mouse embryo chimera assay : Implications that the target involves autocrine growth factor function. / Peters, Jeffrey M.; Tsark, Eleanor C.; Wiley, Lynn M.

In: Radiation research, Vol. 145, No. 6, 06.06.1996, p. 722-729.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Radiosensitive target in the mouse embryo chimera assay

T2 - Implications that the target involves autocrine growth factor function

AU - Peters, Jeffrey M.

AU - Tsark, Eleanor C.

AU - Wiley, Lynn M.

PY - 1996/6/6

Y1 - 1996/6/6

N2 - Mouse preimplantation embryos express at least two functional cell surface growth factor receptors that are radiosensitive in other cell types, the epidermal growth factor receptor (EGF receptor) and the insulin-like growth factor I receptor (IGF-I receptor). These embryos also express ligands that bind to and activate these receptors, including transforming growth factor alpha (TGF-α) and insulin-like growth factor II (IGF-II), which bind to the EGF receptor and IGF-I receptor, respectively. Embryo-expressed IGF-II and TGF-α increase embryo cell number-a measure of proliferation rate- and stimulate blastocoele formation-a measure of cell differentiation-allowing the embryo to self-modulate cell proliferation and morphogenesis into a blastocyst (Paria and Dey, Proc. Natl. Acad. Sci. USA 87, 4756-4760, 1990; Dardik and Schultz, Development 113, 919-930, 1991: Rappolee et al., Genes Dev. 6, 939-952, 1992). In this work, we tested the hypothesis that IGF-I receptor and/or EGF receptor function may be impaired to produce the radiation-induced competitive cell proliferation disadvantage that is expressed by irradiated embryos that are aggregated with nonirradiated embryos in chimeras. Cleavage-stage embryos were irradiated with 137Cs γ rays (0.5 or 1.0 Gy) and paired with nonirradiated same-stage embryos to form groups of chimeras that were cultured in control medium or medium containing IGF-II, insulin, EGF or TGF-α. The cell proliferation disadvantage expressed by the irradiated embryos within chimeras was completely eliminated by IGF- II or insulin. In contrast to the rescue action of IGF-II or insulin in chimeras, neither EGF nor TGF-α could prevent the cell proliferation disadvantage exhibited by irradiated embryos paired with nonirradiated embryos in chimeras. For irradiated conventionally cultured zona-enclosed embryos, IGF-II and TGF-α did not increase mean embryo cell number significantly, although both IGF-II and TGF-α did increase blastocoele formation significantly. Collectively, these results support the following conclusions: (1) Ligands for the IGF-I receptor can rescue irradiated embryos from competitive cell proliferation disadvantage in chimeras, while ligands for the EGF receptor cannot; (2) IGF-I receptor function and EGF receptor function are affected differently by ionizing radiation with respect to competitive cell proliferation and are affected similarly by ionizing radiation with respect to blastocoele formation; (3) EGF receptor-dependent stimulation of competitive cell proliferation and cell differentiation are affected differently by ionizing radiation in preimplantation embryos.

AB - Mouse preimplantation embryos express at least two functional cell surface growth factor receptors that are radiosensitive in other cell types, the epidermal growth factor receptor (EGF receptor) and the insulin-like growth factor I receptor (IGF-I receptor). These embryos also express ligands that bind to and activate these receptors, including transforming growth factor alpha (TGF-α) and insulin-like growth factor II (IGF-II), which bind to the EGF receptor and IGF-I receptor, respectively. Embryo-expressed IGF-II and TGF-α increase embryo cell number-a measure of proliferation rate- and stimulate blastocoele formation-a measure of cell differentiation-allowing the embryo to self-modulate cell proliferation and morphogenesis into a blastocyst (Paria and Dey, Proc. Natl. Acad. Sci. USA 87, 4756-4760, 1990; Dardik and Schultz, Development 113, 919-930, 1991: Rappolee et al., Genes Dev. 6, 939-952, 1992). In this work, we tested the hypothesis that IGF-I receptor and/or EGF receptor function may be impaired to produce the radiation-induced competitive cell proliferation disadvantage that is expressed by irradiated embryos that are aggregated with nonirradiated embryos in chimeras. Cleavage-stage embryos were irradiated with 137Cs γ rays (0.5 or 1.0 Gy) and paired with nonirradiated same-stage embryos to form groups of chimeras that were cultured in control medium or medium containing IGF-II, insulin, EGF or TGF-α. The cell proliferation disadvantage expressed by the irradiated embryos within chimeras was completely eliminated by IGF- II or insulin. In contrast to the rescue action of IGF-II or insulin in chimeras, neither EGF nor TGF-α could prevent the cell proliferation disadvantage exhibited by irradiated embryos paired with nonirradiated embryos in chimeras. For irradiated conventionally cultured zona-enclosed embryos, IGF-II and TGF-α did not increase mean embryo cell number significantly, although both IGF-II and TGF-α did increase blastocoele formation significantly. Collectively, these results support the following conclusions: (1) Ligands for the IGF-I receptor can rescue irradiated embryos from competitive cell proliferation disadvantage in chimeras, while ligands for the EGF receptor cannot; (2) IGF-I receptor function and EGF receptor function are affected differently by ionizing radiation with respect to competitive cell proliferation and are affected similarly by ionizing radiation with respect to blastocoele formation; (3) EGF receptor-dependent stimulation of competitive cell proliferation and cell differentiation are affected differently by ionizing radiation in preimplantation embryos.

UR - http://www.scopus.com/inward/record.url?scp=0029951491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029951491&partnerID=8YFLogxK

U2 - 10.2307/3579363

DO - 10.2307/3579363

M3 - Article

C2 - 8643832

AN - SCOPUS:0029951491

VL - 145

SP - 722

EP - 729

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 6

ER -