520 THE TOCOPHEROLS 



at term. There is also the interesting observation that offspring of rats 

 dosed at critical periods after the 8th day of gestation sometimes show 

 rather extensive umbilical and skeletal defects.^^^ 



Fetal resorption can be prevented by administration of adequate vitamin 

 E at any time during the first week of pregnancy. If the dosage is critical 

 there may be delivery of dead as well as viable fetuses, the latter rarely 

 surviving more than a few days. Less adequate dosage delays fetal death 

 and resorption for varying periods. Under the latter conditions, fetuses at 

 about the 16th day of pregnancy frequently show pronounced changes in 

 the vascular system (stasis, distention, thrombosis, local hemorrhages) 

 and generalized ischemia prior to death, but no obvious lack of hemo- 

 poiesis.^^ 



With prolonged depletion of vitamin E beyond the first few months of 

 reproductive life, there is a progressive increase in vitamin E requirements 

 for the completion of established pregnancies, and also a progressive inter- 

 ference with implantation of the o\aim (i.e., decreased fecundity rate) as 

 age progresses.^"* • ^^ Evidence points to a uterine and not an ovarian dys- 

 function.^^ 



Fetal death and resorption quite comparable to that in the rat, although 

 not studied in great detail, occur in the mouse-^' ^^ and in the hamster.-^ 

 That in the mouse has been attributed to impaired production of histio- 

 trophe.^'^ In the guinea pig there may occur necrosis of the placenta and 

 fetal death,^^ or abortion due to premature separation of the placenta.^^ 

 Defective development of the chick embryo deprived of vitamin E will be 

 discussed later (p. 534). 



b. Ovary 



In rats reared for a year or more on E-low diets, there are no alterations 

 in behavioral estrus, ovulation, fertilization of the ovum, or its early de- 

 velopment and tubal transport.^^ Histologically, macrophages of the ovarian 

 stroma progressively accumulate pigment arising at sites of follicular atresia 

 and luteal regression,^ a phenomenon which is much more marked in the 

 hamster.21 In resorbing rats there is premature regression of corpora lutea, 



33 K. E. Mason, Yale J. Biol. Med. 14, 605 (1942) ; and in Essays in Biology (in honor 

 of H. M. Evans), p. 401, University of California Press (1943). 



33=' B. H. Thomas and D. W. Cheng, Proc. Iowa Acad. Sci. 59, 218 (1952). 



34 G. A. Emerson and H. M. Evans, /. Nutrition 18, 501 (1939). 



.35H. Kaunitz and C. A. Slanetz, Proc. Soc. Exptl. Biol. Med. 66, 334 (1947); /. 

 Nutrition 3G, 331 (1948). 



36 R. J. Blandau, H. Kaunitz, and C. A. Slanetz, /. Nutrition 38, 97 (1949). 



37 P. Soumalainen, Nature 165, 364 (1950). 



38 A. M. Pappenheimer and M. Goettsch, Proc. Soc. Exptl. Biol. Med. 47, 268 (1941). 



39 A. Ingelman-Sundberg, Acta Endocrinol. 2, 335 (1949). 



