THE OESTROUS CYCLE IN THE MOUSE 343 
4, Evidence for the follicles. In the mouse and in most mam- 
mals studied very large follicles are present in the ovaries during 
the prooestrous and oestrous stages and absent during the met- 
oestrum and dioestrous interval. The histological evidence 
from many sources in all mammals studied excepting certain 
primates overwhelmingly points to the presence of large folli- 
cles as the cause of oestrous changes. However, no direct ex- 
perimental proof has yet been produced. 
The cause of long oestrous periods. Animal 20 was diagnosed 
by the smear method to be in stage M, when killed. If this 
diagnosis was correct, degenerative changes should have begun 
in the genital tract and ovulation should have occurred one or 
two days previously. On histological examination, however, 
the epithelium of the vagina and uterus was found to be in an 
actively growing condition and a set of large normal follicles 
were present in the ovaries. Four normal oestrous periods 
had been recorded for the animal and yet the ovaries contain no 
corpora lutea. Consequently, ovulation had not been spontane- 
ous and it is probable that the large follicles present at death 
would not have ruptured had the animal lived. Her present 
oestrus was first apparent four days before her death. Would it 
not seem probable, then, that the continued growth phase in the 
genital tract might (in the absence of ovulation) be directly 
dependent upon the retention of mature ova in large normal 
follicles? If so, this is a strong suggestion as to the cause of 
oestrus. In mice that do not ovulate spontaneously (therefore 
the simplest condition), they are always present during the 
pro-oestrous and oestrous stages and absent or atretic during the 
met- and dioestrum. As the possibility of the corpora lutea 
and the interstitial tissue actively sharing as causes seems slight 
in the mouse, all the evidence points to the presence of large 
normal follicles as the cause of the growth and congestion of 
the anabolic periods and the absence of normal follicles as the 
primary cause of the catabolic periods in the genital tract. 
In animals that ovulate spontaneously, the rupture of the 
follicles is the dividing line between these two phases, while in 
animals that require an added stimulus for ovulation, atresia 
