NUTRITIONAL EFFECTS 



691 



creased during normal human pregnancy 

 (Miller, Ruttinger and Macey, 1954). 



That a relationship exists, between the 

 dietary requirements just described to the 

 endocrine substances which participate in 

 the control of pregnancy, is suggested by the 

 fact that the deleterious effects of a protein- 

 free diet on pregnancy in rats have been 

 counteracted by the administration of es- 

 trone and progesterone. Pregnancy was 

 maintained in 30 per cent, 60 to 80 per cent, 

 and per cent of protein-deficient animals 

 by daily dosages of 0.5 /xg., 1 to 3 fig., and 6 

 jug. estrone, respectively. On the other hand, 

 injection of 4 to 8 mg. progesterone alone 

 maintained pregnancy in 70 per cent of the 

 animals (Nelson and Evans, 1955) , and an 

 injection of 4 mg. progesterone with 0.5 //.g. 

 estrone provided complete replacement 

 therapy (Nelson and Evans, 1954). Food 

 intake did not increase. The results suggest 

 that reproductive failure in the absence of 

 dietary protein was due initially to lack of 

 progesterone and secondarily to estrogen, 

 the estrogen possibly serving as an indirect 

 stimulation for luteotrophin secretion and 

 release. It is well known that hypophysec- 

 tomy or ovariectomy shortly after breeding 

 will terminate a pregnancy and that re- 

 placement therapy requires both ovarian 

 hormones. Thus, the protein-deficient state 

 differs somewhat from the state following 

 hypophysectomy or ovariectomy, but the 

 factors involved are not known. 



Pregnancy alters nutritional and meta- 

 bolic conditions in such a way that labile 

 protein stores of the liver and other parts of 

 the body are influenced, but similar effects 

 are imposed by a transplanted tumor, es- 

 pecially when it reaches 10 per cent of the 

 body weight. ' Thus, transplantation of a 

 tumor into a pregnant animal would place 

 the fetuses in competition with the tumor for 

 the amino acids of the metabolic pool. Under 

 these circumstances will the pregnancy be 

 maintained? An answer to the question may 

 not yet be given. Nevertheless, Bly, Drevets 

 and Migliarese (1955) observed various de- 

 grees of fetal damage in pregnant rats bear- 

 ing the Walker 256 tumor, and 43 per cent 

 fetal loss was obtained with a small hepa- 

 toma (Paschkis and Cantarow, 1958). 



Essential fatty acid deficiency, at least 

 in the initial stages, does not interfere with 



development of the fetuses or parturition in 

 the rat, but the pups may be born dead or 

 they do not survive more than a few days 

 (Kummerow, Pan and Hickman, 1952). A 

 more pronounced deficiency has induced 

 atrophic changes in the decidua, resorption 

 of fetuses, and prolonged gestation. Death 

 of the fetuses appears to be secondary to 

 placental injury. Hormonal involvement, if 

 any, when there is fatty acid deficiency and 

 pregnancy seems not to have been investi- 

 gated. 



Pregnancy and lactation are major fac- 

 tors influencing vitamin requirements. It is 

 not surprising, therefore, that vitamin de- 

 ficiencies influence the course of a preg- 

 nancy. The subject has recently been re- 

 viewed by Lutwak-jMann (1958). 



A deficiency of vitamin A does not no- 

 ticeably affect early fetal development, but 

 later in gestation placental degeneration oc- 

 curs with hemorrhage and abortion. When 

 the deficiency is moderate the pregnancy is 

 not interrupted, but the fetuses are damaged 

 (Warkany and Schraffenberger, 1944; Wil- 

 son, Roth and Warkany, 1953; Giroud and 

 Martinet, 1959). In calves and pigs the 

 abnormalities are associated with the eyes 

 and palate (Guilbert, 1942) ; in birds skele- 

 tal abnormalities are seen (Asmundson and 

 Kratzer, 1952). The use of hormones in an 

 effort to counteract the effects seems to have 

 been attempted only in the rabbit where 

 12.5 mg. progesterone improved reproduc- 

 tion impaired by vitamin A lack (Hays and 

 Kendall, 1956). Vitamin A excess also 

 proves highly detrimental to pregnancy, as 

 resorption and malformations occur. Ad- 

 ministration of excessive vitamin A on days 

 11 to 13 of pregnancy induced cleft palate in 

 90 per cent of the embryos (Giroud and 

 Martinet, 1955) . In another experiment the 

 effect of excessive vitamin A was augmented 

 by cortisone (Woollam and Millen, 1957). 



Vitamin E deficiency has long been known 

 to influence pregnancy in rodents and fetal 

 death appears to precede placental damage 

 and involution of the corpora lutea. Gross 

 observations of the abnormal embryos have 

 been reported (Cheng, Chang and Bairn- 

 son, 1957). Estrogen, progesterone, and lac- 

 togen were not effective in attempts at cor- 

 rective therapy (Ershoff, 1943), but estrone 

 and progesterone markedly reduced the in- 



