BIOLOGY OF EGGS AND IMPLANTATION 



851 



endometrium for a number of days after 

 reaching the uterus. In the mouse, mole, 

 shrew, and guinea pig, the free uterine pe- 

 riod is from 3 to SVk days; in the rabbit, 5 

 to 6 days; in the rhesus monkey and possi- 

 bly the human, 4 to 6 days ; in the cat, 8 to 

 9 days; in the dog, 9 to 10 days; and in the 

 ungulates probably somewhat longer. 



Under the conditions of "developmental 

 diapause" or delayed implantation, the free 

 uterine period of the blastocysts may be 

 significantly prolonged. Delayed implanta- 

 tion occurs naturally in a variety of species 

 such as the pine marten, 6 months; Ameri- 

 can badger, 2 months; European badger, 3 

 to 10 months; European roe deer, 4 months; 

 armadillo, 14 weeks; fishers, 9 months; and 

 bears, 6 months. Delayed implantation has 

 also been recorded in the stoat, weasel, sa- 

 ble, and fur seal. In the rat, mouse, and cer- 

 tain insectivores, implantation may be de- 

 layed several days to 2 wrecks if there is 

 concurrent lactation (Lataste, 1887; Daniel, 

 1910; King, 1913; Hamlett, 1935; Brambell, 

 1937; AVeichert, 1940, 1942). In the mouse 

 and rat the delay varies roughly with the 

 number of young suckled, and this, in turn, 

 prolongs the period of gestation. According 

 to Lataste, the duration of gestation is nor- 

 mal in mice suckling only 1 or 2 young but 

 prolonged in those suckHng 3 or more. If 

 certain hormonal conditions are satisfied, 

 implantation will occur in normal females 

 suckling large litters (Kirkham, 1916; 

 Weichert, 1940, 1942, 1943; Krehbicl, 1941). 

 Delay of implantation is very likely due to 

 an inhibitory effect by some uterine or nu- 

 tritional factor acting on the blastocysts 

 (Whitten, 1958). Various experimental 

 methods may successfully delay implanta- 

 tion without destroying the ova. Ovariec- 

 tomy the second day after mating in the rat, 

 followed by subliminal doses of progester- 

 one (0.5 mg. per day ) , will keep the eggs 

 alive for 6 to 45 days, but the decidual cell 

 response and implantation do not take 

 place. If more progesterone than 0.5 mg. per 

 day is injected into these animals, implanta- 

 tion may occur. A combination of injections 

 in which a small dose of estradiol benzoate 

 is added to the subliminal dose of progester- 

 one is very effective in consummating im- 

 l^lantation. In contrast, if the ovaries are 

 removed from pregnant rats on the fourth 



day when the blastocysts have reached the 

 cornua, progesterone, even in dosages of 10 

 mg., cannot effect implantation. If estrogen 

 and progesterone are injected simultane- 

 ously, the blastocysts will resume their 

 growth and will implant (Canivenc and 

 Laffargue, 1957; Cochrane and Meyer, 1957; 

 Mayer, 1959). 



The blastocysts of pregnant rats spayed 

 the 4th day may remain alive for as long 

 as or longer than 21 days. Rat blastocysts 

 apparently do not reciuire adrenocortical 

 hormones to remain viable. Mayer (1959) 

 and his co-workers have demonstrated that 

 the blastocysts in the cornua of rats which 

 have been ovariectomized and adrenalecto- 

 mized on the 4th day after mating can im- 

 plant on the 10th day, provided estrogen 

 and progesterone are both injected simul- 

 taneously. 



The experiments of Cochrane and Meyer, 

 and others that have been mentioned, sug- 

 gest that the optimal conditions for embryo 

 attachment and implantation depend on a 

 delicately balanced, synergistic action of 

 estrogen and progesterone on the endome- 

 trium. But nothing is known as to what is 

 happening within the egg during its dormant 

 state and what factors control the dor- 

 mancy, nor do we understand what changes 

 occur within the uterine lumen which may 

 eventually satisfy the conditions of the em- 

 bryo to continue its growth, make attach- 

 ment to the uterine epithelium, and implant. 

 Our point of view will no doubt be broad- 

 ened as experimental approaches to the 

 problem are varied and more species are 

 studied. 



Runner <1947), Fawcett (1950), and 

 Kirby (1960) found tliat, irrespective of 

 the state of the host's gonads, im- 

 plantation occurred when mouse ova were 

 transplanted either to the kidney cap- 

 sule or to the anterior chamber of the 

 eye. Whitten (1958) transplanted 8-celled 

 mouse eggs to the surface of the kidneys of 

 normal and hypophysectomized mice. Ten 

 days later successful grafts were found in 

 10 of 15 normal and in 13 of 18 hypophy- 

 sectomized animals. Successful implantation 

 of mouse eggs onto the kidney apparently 

 does not depend on the secretion of the pi- 

 tuitary. 



Buchanan, Enders and Talmage (1956) 



