100 



BIOLOGIC BASIS OF SEX 



effects on the accessory sex structures of the 

 host, similar to those induced by intra-em- 

 bryonic grafts. 



4. Sex Reversal in Vitro 



More recently the technique of culture in 

 vitro has been employed by Wolff and his 

 collaborators with great success to study the 

 development of embryonic gonads, and it 

 has been possible to produce typical reversal 

 of sex differentiation in vitro by two meth- 

 ods. Prospective ovary and testis of the 

 chick or duck, isolated at the very beginning 

 of sex differentiation and placed in close 

 contact in the culture dish,^ become firmly 

 fused, facilitating the transmission of hu- 

 moral influences. As in the case of gonad 

 grafts in the coelomic cavity, the ovary un- 

 der such conditions proves to be the domi- 

 nant gonad (Wolff and Haffen, 1952b). It 

 readily induces cortical differentiation on 

 the testis, which becomes an ovotestis, and 

 may even approximate closely the structure 

 of a normal ovary of the same age (Fig. 

 2.15). The same type of transformation oc- 

 curs in testes after introduction of estradiol 

 benzoate into the culture medium. 



With respect to the histologic character 

 of the reversal process, the resemblances be- 

 tween the effects of gonad grafts implanted 

 in the body cavity, crystalline hormones in- 

 jected into the whole organism, and the re- 

 sults of the same procedures applied to iso- 

 lated gonad primordia in vitro are 

 extremely close. The in vitro studies demon- 

 strate again the autonomous character of 

 the differentiation process, and its flexibility 

 in the presence of extraneous hormones is 

 shown to be independent of the organism 

 as a whole. Hormones in vitro evidently act 

 directly on the gonad mechanism. 



1). TIIK PROBLEM OF SEX REVERSAL 

 IN MAMM.\LIAN GONADS 



1. Bisexual Potentialities in the Emhrijoiiic 

 Gonads of Mam^nals 



In marked contrast with the striking ef- 

 fects of steroid sex hormones on the differ- 

 entiation of the gonads of birds and various 



" Combinations of gonads in the culture dish 

 must initially be made at random but the other 

 gonad of each donor is cultured separately in order 

 to establish its sex. 



species of amphibians has been the failure 

 thus far to ol)tain comparable effects in 

 mammalian embryos with the exception of 

 a single species, the North American opos- 

 sum, a marsupial. Essentially negative re- 

 sults have been reported for a number of 

 species of placental mammal, in which preg- 

 nant females were treated with relatively 

 large dosages of sex hormones during the 

 period of sex differentiation. Experiments 

 of this type were carried out in the rat by 

 Greene, Burrill and Ivy (Greene, 1942), and 

 in the guinea pig (Dantchakoff, 1936, 1937), 

 the mouse (Turner, 1939, 1940; Raynaud, 

 1942j , the rabbit (Jost, 1947 a) , the hamster 

 (Bruner and Witschi, 1946; White, 1949), 

 and the monkey (Wells and van Wagenen, 

 1954). With the single exception of the 

 opossum (to be described later) the modi- 

 fications induced are minor in character and 

 are of three types: (1) a general retardation 

 of growth and development of the gonads, 

 without obvious signs of sex reversal, which 

 occurs in both ovaries and testes and may 

 be produced by either type of sex hormone;'^ 

 (2) a variable degree of hypertrophy of the 

 medullary elements of ovaries after treat- 

 ment with male hormone, reported in only 

 a few cases (Dantchakoff, 1939; Jost, 1947a; 

 Wells and van Wagenen, 1954) ; and (3) the 

 occasional persistence of localized patches 

 of germinal epithelium on the surface of well 

 differentiated testes, a condition which 

 sometimes appears after treatment with 

 either type of sex hormone. IVIinor changes 

 of this character have not generally been 

 accepted as convincing evidence of sex re- 

 versal. 



Notwithstanding this array of negative 

 findings, the failure of the embryonic gon- 

 ads of placental mammals to respond defi- 

 nitely to sex hormones can hardly be at- 

 tributed to an inherent lack of bisexual 

 potentiality. During the early stages of their 

 development they show, histologically, the 

 same evidences of bisexual structure as the 

 gonads of other vertebrates, although typi- 

 cally the bisexual phase is of relatively 

 brief duration and the recessive sex com- 



" This effect is of common occurrence and is 

 best explained as a depression of the gonadotrophic 

 function of the anterior pituitary, a mechanism 

 whicli is well established in adult organisms 

 (Moore and Price, 1932). 



