THE OESTROUS CYCLE IN THE MOUSE 341 
c. The cause of cyclic oestrous changes. Many investigators 
have postulated theories from histological evidence. Since 1900 
the problems have been approached also by experimental methods 
and a complicated mechanism built up on experimental evidence 
to account for oestrous changes. A short review of these re- 
sults seems advisable. 
1. Is the cause of oestrous phenomena inherent in the genital 
tract itself? Heape believed that oestrus and menstruation 
might occur after the removal of the ovaries. Consequently, 
he postulated an extra-ovarian cause of these phenomena. Since 
1900, however, accumulated evidence from spayed animals has 
proved that without the ovaries the oestrous or menstrual cycle 
slowly disappears and the uterus and vagina atrophy. Hal- 
ban and others, and recently Stockard and Papanicolaou (’17), 
have called attention to a cyclic atrophy following ovariotomy. 
This is also evident in the mouse in a periodic appearance at 
intervals equivalent to the oestrous cycle of cornified cells in 
the smear, always in the presence of leucocytes, however. From 
this, cyclic changes inherent in the uterus itself might be implied. 
Without the presence of the ovaries, however, no growth or 
regenerative processes occur. Might not cyclic degeneration 
in the uterus and vagina after spaying be merely secondarily 
induced by ovarian influences? 
Temporarily let us exclude from consideration as improbable 
any inherent cyclic nature of the uterus itself and see if the ova- 
ries may supply the cause. Three structures are present there 
that might be responsible: the follicles, the corpora lutea formed 
after their rupture, and possibly interstitial cells. 
2. The follicles or the interstitial tissue. Large follicles 
distended with liquor folliculi have almost invariably been re- 
ported present during the prooestrous and oestrous periods in 
mammals, although the work of Heape (’98) and Leopold (94) 
throws some doubt on their being always present in the primates. 
Consequently, many investigators believe the ripening follicles 
to be the cause of these phenomena. They are present in all 
mice studied during the prooestrous and oestrous stages. 
