BIOLOGY OF EGGS AND IMPLANTATION 



863 



19591)1 undertook to investigate the na- 

 ture of the non-specific stimulus required 

 to initiate the deciduomas by determin- 

 ing the effects of histamine and histamine 

 antagonists on the endometrium. He the- 

 orized that some degree of injury was 

 a common factor to all methods of 

 uterine stimulation, that a histamine or 

 histamine-like substance was present at 

 the site of injury, and further, that at the 

 time of blastocyst attachment there is an 

 "estrogen surge" which acts to release his- 

 tamine from the endometrium and which in 

 turn initiates the decidual cell response. Evi- 

 dence for the role of histamine in deciduoma 

 production also includes the depletion of the 

 mast cell population of the endometrium just 

 before attachment. On this basis, after in- 

 stilling diphenhydramine hydrochloride or 

 other antihistamines into one horn, both 

 cornua of pseudopregnant rats were stimu- 

 lated to induce deciduoma development. 

 Definite inhibition of deciduoma was noted 

 in the cornu receiving the antihistamine, 

 particularly if the drug was instilled before 

 the transformation of endometrial cells to 

 decidual cells. Consistent with this finding 

 are the indications from extensive tests that 

 drugs having a specific histamine antago- 

 nism are effective in suppressing the de- 

 cidual cell reaction when introduced into the 

 uterine lumen of rats and mice during pseu- 

 dopregnancy. On the other hand, antihis- 

 tamines injected subcutaneously in these 

 animals ordinarily fail to prevent implanta- 

 tion. Species differences must also be con- 

 sidered. Boving (1959) was unable to find 

 mast cells associated with rabbit tropho- 

 blast invasion. 



The theory that some mechanism of his- 

 tamine release is responsible for initiating 

 the decidual cell reaction would logically 

 imply that the blastocyst is an active his- 

 tamine secretor or that it indirectly effects 

 a rise of "free" histamine in the cornua, or 

 interferes with its destruction. In all of the 

 work that has been reported in the attempt 

 to establish histamine as the primary evo- 

 cator in the decidual cell response and im- 

 plantation, the blastocyst has been ignored. 

 There has been no attempt to examine the 

 living blastocyst itself and to determine the 

 effects of the various drugs used on it. Con- 



sequently, the conclusions drawn as to the 

 failure of implantation are equivocal because 

 the condition of the implanting agent in the 

 experiment has not been evaluated. Also rel- 

 evant is the fact mentioned earlier that the 

 decidual response in the rat and mouse is 

 evoked, not only by living embryos, but also 

 by many inert objects inducing the response 

 without evidence of epithelial destruction. 

 The mechanism of histamine release under 

 these conditions must be based on some un- 

 known factor. 



The appearance of implantation cones, 

 just before and durine attachment of the 

 blastocyst to the endometrium in guinea 

 pigs, rabbits, squirrels, chipmunks, and prob- 

 ably primates, raises the question as to 

 whether the embryo may not initially send 

 protoplasmic extensions between the epi- 

 thelial cells lining the lumen and thus se- 

 crete some substance which not only ini- 

 tiates the decidual response, but also effects 

 the removal of underlying endometrial tis- 

 sue (compare Figs. 14.23, 14.24 and 14.25) 

 (Mossman, 1937; Wislocki and Streeter, 

 1938; Boving, 1954, 1959a j. It is interesting 

 that during this initial invasion in the 

 guinea pig, rabbit, and man, there is a 

 negligible amount of endometrial necrosis. 

 In the description of the implantation stages 

 of the macaque, Wislocki and Streeter 

 also emphasized that during the earliest 



INNER CELL MASS 





1 |i|" 'WIF 



ATTACHING ,^ -^^^ mm 



TROPHOBLAST-^^ - •' . ^ « 



Fig. 14 23. Section of a ciuili.'a pig lila.-lo.-yst 

 showing the \eiy earliest stage in the attachment 

 of the abembiyonal pole cells to the maternal 

 endometrium. X 500. 



