518 THE TOCOPHEROLS 



interval.^^ Degeneration is delayed 30 to 40 days by a single dose of 0.5 to 

 1.0 mg. of tocopherol fed on the 15th day of life;^^ yet daily doses of between 

 0.5 and 0.75 mg. are necessary to protect the testis in rats reared 16 to 17 

 months on E-low diets. 2" Prolonged deficiency has no effect on the weight 

 of accessory sex glandsj^" indicating that hormonal functions of the testis 

 are not impaired. 



The degenerative process, which reaches completion in 2 to 3 weeks, 

 affects seminiferous tubules unequally as it progresses. It is characterized 

 by the following sequence of events: (1) inhibition of spermatogenesis, as- 

 sociated with abnormal swelling and fusion of mature sperm; (2) marked 

 diminution in sperm, and nuclear chromolysis in spermatids and second- 

 ary spermatocytes; (3) extensive sloughing of germ cells, and fusion of many 

 into large multinucleate cells; (4) nuclear fragmentation and hydropic de- 

 generation of remaining germ cells; (5) eventually the shrunken tubules 

 are lined by a vacuolated, fibrous Sertoli syncytium. During the degenera- 

 tive process many germ cells are sloughed and transported to the epidi- 

 dymis; others undergo dissolution in situ. Moderate amounts of acid-fast 

 pigment are usually demonstrable in the Sertoli syncytium and in macro- 

 phages of the interstitial connective tissue.^ Leydig cells are normal. The 

 testes are grossly atrophied, brownish, flabby, and watery when cut. 



b. Other Species 



In the hamster there occurs a much more gradual degeneration of the 

 germinal epithelium, accompanied by accumulation of much acid-fast pig- 

 ment in the germ cells and macrophages of the interstitial tissue, but, unless 

 injury reaches an advanced stage, vitamin E therapy results in relatively 

 successful restoration of the germinal epithelium.-^ Testicular degeneration, 

 associated with some pigment, occurs also in the guinea pig if a chronic 

 deficiency is maintained such that symptoms of muscular dystrophy are 

 kept minimal until after sexual maturity ,2- but therapeutic response has 

 not been studied. Testis damage resembling early phases of injury in the 

 rat has been observed in the rabbit,^^ the dog,-^ and the monkey.-^ There 

 is also a suggestion that the germinal epithelium of young pigs is altered 



18 K. E. Mason, Am. J. Physiol. 131, 268 (1940). 



IS H. Kaunitz, A. M. Pappenheimer, and C. Schogoleff, Am. J. Pathol. 20, 247 (1944). 



20 H. M. Evans and G. A. Emerson, J. Nutrition 26, 555 (1943). 



^1 K. E. Mason, Unpublished studies. 



" A. M. Pappenheimer and C. Schogoleff, Am. J. Pathol. 20, 239 (1944). 



" M. L. Chevrel and M. Cormier, Compt. rend. 226, 1854 (1948); Ann. Endocrinol. 



10, 19 (1949). 

 2^K. M. Brinkhous and E. D. Warner, Am. J. Pathol. 17, 81 (1941). 



