852 



SPERM, OVA, AND PREGNANCY 



reported that implantation occurs in ovari- 

 ectomized armadillos that are not receiving 

 hormonal replacement. In the European 

 badger ovulation occurs during delayed im- 

 plantation. The new set of corpora lutea 

 does not hasten implantation because delay 

 in implantation may continue for 2 months 

 after the last ovulation (Harrison and Neal, 

 1959). 



The phenomenon of delayed implantation 

 offers an excellent experimental approach to 

 the general problem of embryo-endometrial 

 interrelationships and the specific factors 

 that control embryo attachment and im- 

 plantation. 



N. SPACING AND ORIENTATION OF OVA 

 7^- UTERO 



The specific sites of implantation in mam- 

 mals having multiple young, as related both 

 to the longitudinal axis and to the surface 

 of the endometrium, are remarkably con- 

 stant (Mossman, 1937). Even in animals 

 having only a single young and a simplex 

 uterus, such as man, monkey, sloths, and 

 others, the location of the implantation site 

 and the orientation of the blastocyst to the 

 endometrium are quite definitely regulated 

 (Mossman, 1937; Heuser and Streeter, 

 1941). 



Various explanations have been proposed 

 to account for the intra-uterine spacing of 

 blastocysts in polytocous mammals. Moss- 

 man suggested that the implanting blasto- 

 cyst may interact in some manner with the 

 surrounding endometrium so as to create a 

 local refractory zone in which no other em- 

 bryos can implant. The results obtained by 

 Fawcett, Wislocki and Waldo (1947) after 

 transplanting several mouse ova into the 

 same anterior chamber of the eye are of in- 

 terest in this connection. They found that 

 fertilized eggs continue to develop in close 

 proximity to one another only until one of 

 them begins to implant. Thereafter, the re- 

 maining embryos degenerate. The onset of 

 the degenerative changes in the surrounding 

 blastocysts is coincident with the extravasa- 

 tion of blood into the tissues in the immedi- 

 ate vicinity of the attaching embryo. They 

 suggest that possibly a cytolytic ferment of 

 the trophoblast may cause edema or hemor- 

 rhage into the maternal tissues which so al- 



ters the local environment that it is unten- 

 able for the remaining blastocysts. 



According to Mossman's theory, the 

 blastocyst that enters the uterine cavity 

 first establishes a refractory zone near the 

 uterotubal junction and begins the process 

 of attachment. The remaining blastocysts 

 establish similar zones in the fashion of a 

 gradient toward the cervix until all become 

 evenly spaced. It has been frequently ob- 

 served in pregnant animals with bicornu- 

 ate uteri that the embryos which are im- 

 planted nearest the oviducts are slightly 

 more advanced in development than those 

 nearest the cervix. It has also been observed 

 that the embryos which are implanted near- 

 est the cervix show a higher incidence of 

 resorption than those implanted at other 

 sites. 



Recently McLaren and Michie (1959) 

 have taken issue with Mossman's theory 

 that implantation is serial and that refrac- 

 tory zones are established. These investiga- 

 tors induced ovulation and mating in mice 

 by hormone treatment. At 18V^ days after 

 mating, the cornua were divided into 6 equal 

 segments and the embryos weighed. They 

 found that the embryos in the middle of the 

 cornua actually weighed less, on the aver- 

 age, than those at either end. The embryo 

 lying nearest the oviduct was usually sig- 

 nificantly lighter than its neighbor. 



It may be questioned whether the differ- 

 ences in weight of mice fetuses at ISV^ days 

 post coitum have any relationship to differ- 

 ences in size and differentiation of the em- 

 bryos during the first 5 to 10 days of devel- 

 opment or during the period of orientation 

 in utero or of attachment and implantation. 



Investigators who have observed blasto- 

 cysts and implanting embryos have fre- 

 quently commented on the variations in the 

 early stages of development in the same ani- 

 mal and the variation from animal to ani- 

 mal when they are killed at identical times 

 after mating. The variations in the rate of 

 differentiation are particularly striking if 

 the development of the attachment cones of 

 the guinea pig embryos are observed in tis- 

 sue culture. The attachment cones of each 

 of the 2 to 3 blastocysts recovered from the 

 cornua of the same animal may be in a dif- 

 ferent stage of development and may retain 



