MAMMALIAN REPRODUCTn'E CYCLE 



539 



SIR' which had been killed by freezing had 

 no such effect, nor did successful grafts of 

 uteri from diestrous donors. Bradbury, 

 Brown and Gray (1950) found that par- 

 tially hysterectomized rats in which the re- 

 maining uterine tissue was continuous with 

 the cervix, hence properly drained, experi- 

 enced pseudopregnancies of normal length. 

 However, when the continuity was inter- 

 rupted the uterine remnants became greatly 

 distended, the endometrium was destroyed, 

 and the animals had prolonged pseudopreg- 

 nancies. Possibly the endometrium is the 

 source of the hypothetical "luteolytic" sub- 

 stance.*' 



Under other circumstances the endome- 

 trium of rats has a luteotrophic rather than 

 luteolytic effect, for when deciduomas are 

 induced by trauma the pseudopregnancies of 

 otherwise normal animals are lengthened to 

 22 days or more (Ershoff and Duell, 1943; 

 Velardo, Dawson, Olsen and Hisaw, 1953). 

 This is not true in mice, however, and Ka- 

 mell and Atkinson (1948) suggest that the 

 I'eason may lie in the shorter life-span of the 

 decidual tissue in that species. Loeb (1927) 

 reported that deciduomas in cyclic guinea 

 pigs ])rolonged the luteal phase, i.e., delayed 

 the next ovulation from 3 to 7 days, which 

 is far less than the prolongation after hys- 

 terectomy. 



As an alternative to the concept of con- 

 I rol of the corpus luteum by humoral agents 



" The denial by Velardo, Olsen, Hisaw and 

 Dawson (1953) that hysterectomy in rats prolongs 

 l)seiidopregnancy is based on operations performed 

 later in the luteal phase than those of Bradbury, 

 Brown and Gray and of Hechter, Fraenkel, Lev 

 and Soskin. Whereas the latter workers had op- 

 erated in the range from the 4th to the 7th day.^^ 

 of p.seudopregnancy and many of Bradbury's 

 cases lacked uteri when they entered pseudopreg- 

 nancy, Velardo and associates excised the uteri 

 on the 9th day. It seems possible that this dif- 

 ference in time may be crucial, for by the 9th 

 day of a 12-day pseudopregnancy the corpora 

 lutea must be on the verge of regression, if that 

 in'ocess has not already been initiated. After 

 maintaining pseudopregnancy in estrogenized, 

 liypophysectomized rats b}^ means of lactogen, 

 its withdrawal is followed about 3 days later by 

 estrous smears (Nelson and Bichette, 1943; Nel- 

 son, 1946). A slightly longer delay occurs in non- 

 estrogenized, intact rats at the end of a lactogen- 

 induced pseudopregnancy (Everett, unpublished) 

 or after withdrawal of progesterone treatment 

 (Fig. 8C). 



formed in the uterus, Loeb considered the 

 jjossibility that neural mechanisms are in- 

 volved. The idea was not acceptable, he felt, 

 because in partial hysterectomies the result 

 was not detennined by the locus of the part 

 removed. The finding by Hechter, Fraenkel, 

 Lev and Soskin (1940) that grafts of uterine 

 tissue in hysterectomized rats return the 

 duration of pseudopregnancy to normal, is 

 significant evidence pointing in the same di- 

 rection. 



A third hypothesis was advanced by 

 Heckel (1942) who found in rabbits that 

 the extent of prolongation of luteal func- 

 tion by subtotal hysterectomy is roughly 

 proportional to the amount of uterine tis- 

 sue removed. The suggestion was offered 

 that removal of the uterus has an estrogen- 

 sparing effect. The greater amount of estro- 

 gen thus available to the corpora lutea pro- 

 longs their life, according to this view. 



Later investigations by Moore and Nal- 

 bandov (1953) revive the possibility that 

 the uterus influences the ovary by way of 

 the nervous system. In sheep the implanta- 

 tion of a plastic bead in utero during the 

 early luteal phase shortened the cycle by 

 several days. Successive cycles tended to be 

 unusually short. When the uterine segments 

 containing the beads were denervated, how- 

 ever, the cycles were essentially normal. 

 Other work from the same laboratory (Hus- 

 ton and Nalbandov, 1953) which indirectly 

 may bear on this problem, indicates that 

 the presence of a mechanical irritant (a 

 thread) in the oviduct of the domestic fowl 

 tends to block ovulation. The blockade may 

 extend for as long as 20 days if the thread 

 is placed in the isthmus (van Tienhoven, 

 1953). The ovaries remain functional, pro- 

 ducing large follicles which may be ovulated 

 at will by injection of LH. The authors feel 

 that this phenomenon, like the effect of the 

 bead in the sheep uterus, involves a neural 

 mechanism, Init crucial information is lack- 

 ing. It may be significant that stimulation 

 of the ovaries was found in some hens, in 

 place of blockade. 



We may hope that as more information 

 becomes available the assortment of facts 

 given in these paragraphs will fit into a 

 rational system. Not until this is realized 

 can we hope to understand the regulation of 

 the luteal phase. 



