710 



Teratogenesis 



instances: the cloacal region of chick embryos 

 (Boy den, '22), limbs in mice (Chang, '40) 

 and other embryos, the brain of human and 

 chick embryos (Gruenwald, '45), etc. The 

 morphogenetic importance of these foci has 

 occasioned some speculation but is, in most 

 instances, still obscure (Ernst, '26; Peter, '36; 

 Gliicksmann, '51). It is likely that these foci 

 are, under normal conditions, kept localized 

 by inhibitory factors. It is conceivable that 

 the inhibition may be lost under certain cir- 

 cumstances and that the degenerative foci 

 may involve more extensive areas and cause 

 more permanent destruction than one en- 

 counters normally. An example which seem- 

 ingly involves this type of excessive destruc- 

 tion is found in the dominant rumpless mu- 

 tation of chicks discussed above (p. 703). In 

 normal embryos there is a focus of degener- 

 ating cells posterior to the tail bud which 

 represents the remnant of the primitive 

 streak. As a result of the formation of the 

 tail fold this group of cells comes to lie in 

 the region of the cloaca and concomitantly 

 thii-re is an increase in the number of de- 

 generate cells. The latter become, during the 

 third and fourth days, involved in the events 

 leading to the formation of the cloaca and 

 anus (Boyden, '22). In the dominant rump- 

 less embryos it appeared that the degenera- 

 tive process did not remain restricted to the 

 anal plate but spread to the undifferentiated 

 tail bud. 



Failure of Degeneration to Occur. A final 

 possible involvement of degenerative proc- 

 esses in the production of anomalies is their 

 failure to occur as part of a normal develop- 

 mental sequence. All students of anatomy 

 are familiar with such instances. It will suf- 

 fice to mention a few of the well known ex- 

 amples of this sort. Persistence of the thymus 

 gland beyond the stage when fatty degener- 

 ation normally sets in is a familiar case. 

 There are instances in which various of the 

 primitive aortic arches fail to degenerate. 

 Probably the persistence of the right fourth 

 aortic loop with the resulting two aortae is 

 one of the most striking of these. In like man- 

 ner the failure of the ductus arteriosus to 

 undergo its fibrotic degeneration (and the 

 resultant "bkie baby") is classic. For details 

 of this type of anomaly see Patten ('46) and 

 Arey ('54). 



ABNORMALITY OF FUNCTIONAL AC- 

 TIVITY OR REGULATORY MECHANISMS 



Under this heading are included anomalies 

 which resvilt directly from a gross disturb- 



ance of function and from hormonal imbal- 

 ance. It has been pointed out previously, and 

 should be emphasized again, that all of the 

 malformations described in this chapter must 

 be the visible expressions of distvirbances of 

 physiological processes. Those discussed here 

 are cases in which these disturbances are 

 more obviously related to the teratological 

 development. 



Bonnevie ('36, '43) has investigated two 

 mutations in mice in which excess of fluid 

 production by the choroid tissue of the brain 

 produces different effects. In the first (Bagg 

 and Little's x-ray-induced mutation) the ex- 

 cess fluid escaped from the brain and, after 

 flowing under the epidermis along the con- 

 cavities of the body, formed blebs in various 

 places (over the eyes, at the distal end of the 

 limbs, etc.). Eventually the blebs became 

 filled with clots of extravasated blood. The 

 abnormal local pressures caused by the clots 

 result in various anomalies [club-feet, syn- 

 dactyly, hypodactyly and congenital ampu- 

 tation (Bagg, '29)]. In the other mutation 

 the choroid plexi start producing the excess 

 fluid during the twelfth day of gestation. The 

 result is a fairly typical hydrocephalus, since 

 the fluid does not escape (see Mechanical In- 

 terference with Response, above, for effects 

 of deficient pressure in the brain and its re- 

 lation to defects of the ears). 



The well known effects of hormonal im- 

 balances have their parallel in embryonic 

 life. Fugo ('40) has demonstrated that when 

 the pitviitary gland was removed (from chick 

 embryos of 33 to 38 hours), growth was re- 

 tarded. The retardation became very marked 

 after the sixteenth day of incubation. In ad- 

 dition the feathers, thyroid glands, testicu- 

 lar intertubular tissue and yolk-sac with- 

 drawal were abnormal in the later stages of 

 development. The general similarity of the 

 effects of this experimentally produced de- 

 ficiency to hereditary cases of pituitary mal- 

 function is marked despite the fact that in 

 the best known cases of the latter (pituitary 

 dwarfism of mice) it is evident that the aber- 

 rant development does not begin vmtil after 

 birth (Francis, '44). 



GENERALIZATIONS 



In this section are indicated certain gen- 

 eralizations which may be drawn from a 

 study of experimental teratogenesis. It is 

 quite evident that this information may 

 relate to some of the occasional or sporadic 

 terata. However, this section is chiefly in- 

 tended to clarify some of the problems and 



