EXPERIMENTAL PRODUCTION OF HYPOTYPICAL OVARIES. 113 



influences, or that with the growth of the follicles the nourish- 

 ment becomes more difficult, and that this unfavorable state of 

 the cells makes them more vulnerable, if injurious conditions 

 arise. In case the second interpretation should be correct we 

 would have to assume that the process of degeneration leads 

 auto-katalytically to further destruction of the follicles of the 

 remaining granulosa cells. 



These observations lead furthermore to the conclusion that 

 the formative stimuli, which call forth cell proliferation, are not 

 identical with the food stuffs on which ultimately the life of the 

 cells depends and which are therefore necessary for cell multi- 

 plication, a conclusion in full accord with other facts which may 

 be discussed in another connection. Our previous observations 

 and especially the additional observations of Walsh enable us to 

 state the character of the formative stimulus which acts on the 

 granulosa cells. As far as we can determine this stimulus ema- 

 nates from the egg, and affects principally those granulosa cells 

 nearest the egg, but to a less extent also the more distant cells. 

 It is probable that this stimulus increases simultaneously with 

 the growth of the follicles from small to medium size. In the 

 medium-sized follicles it reaches a maximum. From now on 

 certain unfavorable factors begin to make themselves felt with 

 increasing severity and they lead ultimately either to a degenera- 

 tion of the granulosa or to that increased differentiation which 

 is characteristic of maturation of the follicles. Perhaps it is the 

 difficulty in the nourishment of the granulosa a difficulty which 

 increases with the further enlargement of the medium follicles 

 which is the factor which counteracts the cumulative action of 

 the ovum and prevents a steady increase in proliferative power 

 of the granulosa cells, and which ultimately leads to their death. 

 Thus may be explained the typical growth curve consisting of an 

 ascending and a descending branch as has been described by 

 Walsh. As we stated above, the ova in the follicles which in 

 the hypotypical ovary undergo a premature atresia, show pro- 

 gressive changes. Thus the same factor that causes destruction 

 of the granulosa cells acts on the eggs as a stimulus. In a 

 similar manner connective tissue cells show activity, migrate 

 into the follicular cavity and thus contribute to the atresia of 

 follicles under conditions in which the granulosa cells perish in 



