THE CELLULAR BASIS AND AETIOLOGY OF THE LATE 

 EFFECTS OF IRRADIATION ON FERTILITY IN FEMALE 



MICE 



W. L. EUSSELL and E. F. OAKBERG 



Biology Division, Oak Ridge National Laboratory, '\' Oak Ridge, Tennessee, U.S.A. 



SUMMARY 



The degree of irradiation-induced shortening of the reproductive life-span in female 

 mice varies with dose-rate, age of female, and other factors. The basic pattern of this 

 response is accounted for by the amounts of killing in the pool of oocytes in immature 

 follicle stages. Thus, an effect on fertihty, which, at low doses or low dose-rates, is long- 

 delayed in appearance, traces back to cell deaths occurring witliin 24 hours after 

 irradiation. 



One of the late somatic effects of irradiation for which it may be instructive to 

 consider the cellular basis is the effect on reproductive life-span in female 

 mammals. No attempt will be made here to review all the publications on the 

 late effects of irradiation on female fertility. The purpose of this paper is to 

 emphasize that what, until recently, seemed to be a complex phenomenon, with 

 conflicting results from different investigators, now appears to have a rela- 

 tively simple aetiology, at least in its broad aspects. For the demonstration 

 of this point, it will be necessary to cite only cogent samples of the experi- 

 mental findings. Discussion will be restricted to the mouse and rat, because 

 the details have been worked out more thoroughly in these species. The general 

 nature of the aetiology may turn out to be similar in other mammals, but, 

 since marked differences have been noted in the stage at which oocyte 

 development is arrested in the adult (Oakberg and Clark, 1961a), the quantita- 

 tive nature of the response may vary considerably in different mammals. 



Sterility induced in female mice by acute irradiation was clearly shown 

 by Brambell and Parkes (1927), and by Murray (1931), to be due to destruc- 

 tion of oocytes. The same results were obtained by Ingram (1958) for 

 the rat. When later workers turned to the study of dose fractionation 

 and lowered dose-rate, however, some of the results appeared to be in dis- 

 agreement with one another. Thus, some investigators reported that fractiona- 

 tion of dose lessens the sterilizing action of radiation; others reported no 

 effect of lowered dose-rate; and still others reported an increased damage when 

 dose-rate is reduced. It has been demonstrated, however, that these apparent 



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