Adaptation of postimplantation embryos to culture: membrane lipid synthesis and response to valproate.
The environment of the conceptus in culture is quite different from that in utero. It is likely that the embryo adapts to this environment in various ways, but little is known of adaptation, nor of its significance to mechanistic studies using embryo culture. To illustrate this area, we summarize data from two comparative studies: of membrane lipid synthesis by conceptuses in culture and in utero, and of the morphologic response of conceptuses to valproate in these two environments. The synthesis of the major membrane lipids, cholesterol and phospholipids, is significantly affected by culture. De novo synthesis of cholesterol progressively increases during culture, compared to equivalent stages in utero. In contrast, phospholipid synthesis decreases in culture. Cultured conceptuses were morphologically similar to those in utero, suggesting that apparent structural normality does not guarantee biochemical activity equivalent to that in vivo. Conceptuses exposed to valproate in vivo showed a wide range of severity of defects. Those abnormalities that apparently permit survival to term seem relatively subtle, while more severe defects (as usually reported in culture studies) appear to be lethal. Subtle defects, very similar to those induced in vivo, can be reproduced in culture, but only with short-term, not continuous, exposure. We have previously proposed that valproate may interfere with embryonic lipid synthesis. Thus, despite lipid synthetic pathways adapting to the culture environment, the response to valproate in vitro, can mimic that in utero, with appropriate exposure conditions.
Brown
N A
NA
MRC Experimental Embryology and Teratology Unit, St. George's Hospital Medical School, University of London, United Kingdom.
Clarke
D O
DO
McCarthy
A
A
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005260:Female; D008563:Membrane Lipids / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D014635:Valproic Acid / Q000494:pharmacology*; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism
D008563:Membrane Lipids; D010743:Phospholipids; D014635:Valproic Acid; D002784:Cholesterol