82 THE MAMMALIAN EGG 



tion. When attachment occurs, processes from the abembryonal 

 cells can be seen passing between the cells of the uterine epithelium. 

 The zona pellucida is generally shed soon after attachment has been 

 effected. Similar protoplasmic processes are reported to develop in 

 mouse blastocysts cultured in vitro (Whitten, 1957). In the rat, it 

 has been found that eggs recovered just before implantation fre- 

 quently lack the zona pellucida and in many of those that are still 

 entire the embryo is found protruding in part through a hole in 

 the membrane, as if in the act of escape (Z. Dickmann, personal 

 communication, i960). Possibly, pre-implantation escape of the 

 rat embryo from the zona pellucida is effected by the same means 

 as post-implantation escape in the guinea-pig. It is also tempting to 

 suppose that the mechanism by which the protoplasmic processes 

 traverse the zona pellucida may be the same as that employed by 

 the spermatozoon in its penetration into the egg. 



During their free existence, from ovulation to implantation, eggs 

 and embryos have a measure of independence from the maternal 

 organism and enjoy some protection from many of the environ- 

 mental influences that exert effect upon the mother. They are not, 

 however, completely immune to interference. Disturbance in the 

 rate of their transport to the uterus and alteration in the properties 

 of the tubal and uterine secretions can result in death of pre-implan- 

 tation embryos — both effects can be produced by injections of agents 

 such as oestradiol, ethinyl-oestradiol, diethylstilboestrol, oestriol 

 and testosterone (Burdick, Emmerson and Whitney, 1940; Burdick 

 and Pincus, 1935; Burdick and Whitney, 1937; Burdick, Whitney 

 and Pincus, 1937; Parkes, Dodds and Noble, 1938; Pincus and 

 Kirsch, 1936; Velardo, Raney, Smith and Sturgis, 1956; Whitney 

 and Burdick, 1936, 1937). In addition, several antimitotic agents, 

 such as D-usnic acid and more especially podophyllotoxin, have 

 been found on injection into rats to be lethal to the free embryos in 

 doses well tolerated by the mother (Wiesner and Yudkin, 1955). 

 Similar results were reported for the triphenyl ethanol derivative 

 known as MER-25, when given by oral administration to rats and 

 rabbits (Segal and Nelson, 1958 ; Chang, 1959b), and for 6-mercapto- 

 purine, 8-azaguanine, tricthylene-thiophosphoramide (Thiotepa), 

 /y-bis-i, 6-chloroethylamino-D-mannitol (Degranol), triethyleneme- 

 lamine (TEM), N-desacctylmethyl-colchicine (Colcemide) and 

 N-desacetylthiol-colchicine (Thiolcolceran) when injected into 

 rabbits (Hay, Adams and Lutwak-Mann, i960). 



