Blastocoel expansion in the preimplantation mouse embryo: stimulatory effect of TGF-alpha and EGF.
The factors that promote blastocoel expansion in the preimplantation mouse embryo are not well understood. Since cAMP stimulates the rate of blastocoel expansion and, in other systems, EGF can elevate intracellular cAMP levels, we investigated the ability of either TGF-alpha or EGF to stimulate the rate of blastocoel expansion in the mouse. Picomolar concentrations of either TGF-alpha or EGF stimulate the rate of blastocoel expansion in a concentration-dependent manner, and the continual presence of the growth factor is required to observe the stimulatory effect. Neutralizing antibodies to either TGF-alpha or EGF inhibit the TGF-alpha or EGF stimulatory effect, respectively. An antibody to the extracellular domain of the EGF receptor stimulates the rate of blastocoel expansion in a concentration-dependent manner, whereas an antibody to the cytoplasmic domain of the receptor does not. Tyrphostin RG 50864, which inhibits the EGF receptor kinase activity, inhibits the TGF-alpha stimulation of the rate of blastocoel expansion in a concentration-dependent manner; the less active tyrphostin, RG 50862, has no inhibitory effect. In addition, TGF-alpha does not stimulate a precocious onset of cavitation. The stimulatory effect on the rate of blastocoel expansion elicited by TGF-alpha or EGF is observed in 70% of the embryos (responders). Responders and nonresponders have similar intracellular ATP levels and cell numbers. Whereas TGF-alpha stimulates the uptake of [35S]methionine into the acid-soluble and acid-insoluble pools in the responders, TGF-alpha has no stimulatory effect in the nonresponders. Results of these experiments suggest that an initial differentiative function of the first mammalian epithelium--fluid transport--is sensitive to peptide growth factor modulation.
Dardik
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A
Department of Biology, University of Pennsylvania, Philadelphia 19104-6018.
Schultz
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RM
D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000494:pharmacology; D013268:Stimulation, Chemical; D016211:Transforming Growth Factor alpha / Q000494:pharmacology / Q000502:physiology*; D020032:Tyrphostins
D002396:Catechols; D006131:Growth Inhibitors; D009570:Nitriles; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D004815:Epidermal Growth Factor