Effects of alcohols on murine preimplantation development: relationship to relative membrane disordering potency.
During in vitro culture of murine preimplantation embryos, we have observed that exposure to 0.1% ethanol induces an immediate increase in intracellular calcium levels and subsequently accelerates embryogenesis. If the observed effects of ethanol on developing embryos is mediated by its membrane disordering potency, we hypothesized that the relative membrane disordering potencies of related alcohols would correspondingly effect embryonic intracellular calcium levels and developmental rates. Two-cell embryos were exposed to 0.1% ethanol or 0.05 to 1.0% (w/v) n-butanol, n-propanol, isopropanol, 1,2-propanediol, glycerol, or methanol for 24 hr at 37 degrees C, and development to the blastocyst stage was monitored after 5 days. n-Butanol, n-propanol, isopropanol, and methanol treatment caused a dose-dependent inhibition (p < 0.01) of development to the blastocyst stage, whereas 1,2-propanediol or glycerol neither accelerated nor inhibited development. In a second experiment, 8-cell morulae were treated with 1,2-propanediol or glycerol, and cavitation rates were examined. There was no significant difference from control embryos in the onset of cavitation or the blastocoel expansion rate of 1,2-propanediol- or glycerol-exposed embryos, whereas exposure to 0.1% ethanol accelerate cavitation (p > 0.05). In a third experiment, morulae were exposed to 0.1% or 1.0% of each alcohol and were monitored for changes in intracellular calcium levels using the fluorescent indicator, fluo-3-acetoxymethyl ester. There was an immediate increase in intracellular calcium levels when morulae were treated with 1.0% ethanol or n-butanol, but only ethanol induced an increase (p < 0.05) in the level of intracellular calcium at 0.1%. These data suggest that ethanol is unique in its ability to accelerate embryogenesis and that the membrane disordering potency of ethanol does not directly underlie its effects on intracellular calcium release and the acceleration of preimplantation development.
Kowalczyk
C L
CL
C. S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA.
Stachecki
J J
JJ
Schultz
J F
JF
Leach
R E
RE
Armant
D R
DR
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D001755:Blastocyst / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D066298:In Vitro Techniques; D051379:Mice
D000438:Alcohols; D000431:Ethanol; D002118:Calcium