476 



Special Vertebrate Organogenesis 



tiation period, of gonads or gonad tissue in 

 various ways (including the union of whole 

 embryos — parabiosis); and treatment of the 

 embryo with hormones. For technical reasons 

 grafting methods have been largely confined 

 to embryos of amphibians and birds. 



Grafting Experiments. In amphibians the 

 results of grafting the gonad primordium and 

 of parabiosis (Fig. 181) are essentially the 

 same. In combinations of the same sex, 

 gonad differentiation is normal, but in un- 

 like combinations one sex undergoes inhibi- 

 tion or reversal. Typically the male gonad 

 is dominant, but with marked disparity in 

 size or rate of development (as in certain 

 heteroplastic combinations) the ovary may 



5' ;/• ': i^>^^ 



hormones in avian development. Gonads, or 

 gonad tissue, grafted to the chorio-allantois 

 failed to modify the sex structures of host 

 embryos, or to be themselves modified (for 

 reviews see Willier, '39, '52). It was eventu- 

 ally shown, however, that grafts to the em- 

 bryo itself are effective (Wolff, '46). Ovarian 

 grafts induce cortical differentiation on the 

 embryonic testes of the host, but host ovaries 

 are not modified by testis grafts. Evidently 

 in birds the ovary is the dominant gonad. 

 Administration of Hormones. Reversal of 

 differentiation by treatment with pure hor- 

 mones follows a similar pattern. Amphibian 

 larvae treated during the differentiation 

 period develop vai*>ang degrees of intersexu- 



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^X^ 



•::o^ 







V1# 



Fig. 182. Sections, in anterior-posterior sequence, through the testis of a salamander, ioined in parabiosis 

 with a much larger female of another species. Various stages are shown in the conversion of a testis to an 

 ovary by degeneration of the medulla and development of the cortex. (From Burns, '35.) 



predominate. Histologically, reversal involves 

 inhibition and gradual involution of the 

 genetically dominant component, accom- 

 panied by differentiation of the recessive 

 (Fig. 182). Reversal may end in complete 

 functional transformation (see Humphrey, 

 '44, '45, '48), or incomplete dominance may 

 lead to prolonged intersexuality. Removal of 

 the graft causing reversal may then permit 

 reversion to the original sex (for reviews see 

 Willier, '39; Witschi, '39; Humphrey, '42). 

 The results depend in detail on various ex- 

 perimental conditions: the relative size and 

 rate of development of the gonads (or grafts), 

 and the time relations of the experiment. In 

 addition to such variables, pronounced spe- 

 cies and race differences are known (see 

 Witschi, '34, '39) which are reflected in the 

 composition of the gonads, with respect to 

 the representation of medulla and cortex, 

 or the intensity and timing of humoral 

 activity. These differences evidently have a 

 constitutional basis. 



In birds the problem has been studied 

 mainly in the chick embryo. For a long time 

 there was serious doubt as to the role of 



ality, according to experimental conditions 

 and species. Two methods have been used: 

 direct injection during the differentiation 

 period, and immersing the subjects in aque- 

 ous solutions of the hormone. As in grafting 

 experiments, the histological picture in trans- 

 forming gonads shows involution of one 

 gonad component and gradual emergence of 

 the other, according to the sex type of the 

 hormone. Early treatment frequently in- 

 duces complete transformation in either sex 

 (for reviews see Gallien, '44, '50). In some 

 cases, however, large doses may have exactly 

 opposite effects; for example, a female hor- 

 mone may completely masculinize female 

 gonads (see Padoa, '36, '38, '42; Gallien, '41, 

 '44). Such "paradoxical effects" do not occur, 

 however, at low dosages; and it has been 

 shown further that the same hormone, imder 

 the same conditions, may have a feminizing 

 effect at low dosages, produce intersexes at 

 intermediate levels, and have only a mas- 

 culinizing effect at high dosages (e.g., Padoa, 

 '38, '42; Witschi, '51b). Other examples of 

 paradoxical effects will be found and their 

 significance will be considered later. 



