242 PHYSIOLOGIC GENETICS 



decrease in the embryonic liver, and that a maternal excess of vitamin A results in some 

 increase of vitamin A in the embryonic liver. 434 The teratogenic effects of radiation 

 are not due to secondary effects of maternal whole-body irradiation. 1391 Trypan blue 

 has never been observed in the tissues of the embryo, but has been demonstrated in the 

 yolk-sac fluid of rabbit embryos on the seventh, eighth, and ninth days of pregnancy. 357 

 Wilson et al. 1393 have presented evidence to suggest that the yolk-sac epithelium in the 

 rat protects the embryo after the eighth day of gestation by absorbing and immobilizing 

 the dye. Variation in the protective efficiency of the uterine barrier from stage to 

 stage of gestation is an interesting aspect of teratology that needs further investigation. 



The physiology of the mother undoubtedly influences the effect of the teratogen in 

 some cases. For instance, the frequency of cortisone-induced cleft palate in mice 

 decreases with increasing maternal weight. 677 This not only means that this variable 

 must be taken into account when designing experimental controls, but raises the 

 question of its biochemical significance. What aspect of the mother's metabolism is 

 involved, and does it influence the mother's reaction to the teratogen, or have some 

 effect on the embryonic developmental pattern that influences the embryo's response ? 

 Or both? 



Reciprocal cross differences in response to a teratogen suggest the importance of 

 the maternal environment in determining the embryo's reaction to the teratogen. 

 For instance, the frequency of cortisone-induced cleft palate 404 was much higher in F 1 

 hybrids from a cross between A/Jax female mice and C57BL males, than from the 

 reciprocal cross (the A/Jax inbred strain being more susceptible than the C57BL). 

 Backcrosses ruled out a permanent cytoplasmically inherited factor as the source of 

 the difference. 679 Differences in maternal metabolism or placental transmission of 

 the drug were possible explanations, although the latter seems unlikely if the placenta 

 is constituted from fetal tissues, since the two types of hybrids are genetically similar. 

 Another explanation was suggested by studies on the developmental pattern of the 

 embryos. In crosses that produce embryos with a high frequency of cleft palate 

 following maternal treatment with cortisone, the palate, in untreated animals, tends to 

 close later than it does in crosses that are more resistant to the cortisone treatment. 1329 

 The palate closes later in A/Jax than in C57BL/6 embryos, and later in A/Jax $ x 

 C57BL (J than in C57BL/6 $ x A/Jax $ embryos. Thus there is no need to invoke a 

 difference in the way the mother handles the cortisone to account for the reciprocal 

 cross difference in cleft palate frequency, although this has not been entirely ruled out. 

 The difference in response to the teratogen can be accounted for simply as the result 

 of a difference in developmental pattern resulting from the interaction of maternal 

 and fetal genotype. 



The techniques for transfer of ovum and embryo would be an elegant way to 

 analyze further the interactions of embryonic genotype, maternal, and cytoplasmic 

 factors in determining the embryo's response to environmental teratogens; 485, 826 but 

 such an approach so far does not seem to have been used for this purpose. 



Extrinsic variables influencing the probability that a given embryo will have a 



