HORMONES IN DIFFERENTIATION OF SEX 



83 



now been achieved in both mammals and 

 birds, and improved methods of culturing 

 embryonic organs in vitro have made is pos- 

 sible to observe for a sufficient time the de- 

 velopment of sex primordia in complete 

 physiologic isolation. 



Since 1947 castration has been success- 

 fully performed in amniote embryos by two 

 techniques, surgical castration and irradia- 

 tion of the gonad region (for summaries see 

 Jost, 1950; Wells, 1950; Raynaud, 1950; 

 Wolff, 1950; Huijbers, 1951). In all cases 

 serious failures of sexual differentiation fol- 

 low removal or destruction of the gonads. 

 Finally, the cultivation in vitro of indi- 

 vidual sex primordia in virtual absence of 

 hormonal influences has yielded results simi- 

 lar in all respects to those of castration. The 

 results of these experiments will be taken 

 up in detail as they relate to the develop- 

 ment of particular structures. 



in. The Bisexual Organization of the 



Early Enihryo as the Basis of 



Sex Reversal 



The capacity of vertebrate embryos to 

 undergo a reversal of sex, either spontane- 

 ously, as in various developmental anoma- 

 lies of undetermined etiology ("intersexu- 

 ality," "hermaphroditism"), or as a result 

 of experiment, is based on the fact that every 

 individual, regardless of genie sex constitu- 

 tion, passes in early development through a 

 sexually undifferentiated or ''indifferent" 

 phase. During this period virtually all of 

 the embryonic structures necessary for the 

 development of either sex are laid down 

 morphologically and are present for a cer- 

 tain time as discrete 'primordia. The extent 

 to which the primordia of the genetically 

 recessive sex are developed and the length 

 of time during which they are present 

 vary in different groups and species. This 

 fact is of great importance in the experi- 

 mental transformation of sex. In species in 

 which the structures of the recessive sex are 

 imperfectly represented, or are present for 

 only a brief period in early development, 

 opportunity for sex reversal is correspond- 

 ingly limited; but in other cases the rudi- 

 mentary structures of the recessive sex (as 

 for example Miillerian ducts in males or 

 vestigial prostatic glands in females) per- 

 sist indefinitely and mav even survive in the 



adults of some species. The existence of a 

 considerable degree of embryonic bisexual- 

 ity in most groups (see Fig. 2.22) provides 

 a definite morphologic basis for experi- 

 mental transformation of sex and for the 

 sporadic occurrence of sex anomalies as well. 

 The derivation of the various embryonic 

 primordia which give rise to the male and 

 female genital systems, and their history 

 in the normal differentiation of sex, have 

 been extensively reviewed by AVillier (1939) 

 and will not be taken up again in detail. 

 The main features of normal development 

 will be outlined briefly when dealing with 

 the experimental behavior of individual 

 structures. It must be remembered, however, 

 that the individual parts of the genital sys- 

 tem have widely different embryonic origins, 

 and are morphologically and physiologically 

 very dissimilar, and at any particular stage 

 of development may vary greatly in their 

 relative maturity and so in their reactivity 

 to hormones. Many of the basic structures 

 (e.g., the embryonic sex ducts, the urino- 

 genital sinus) are taken over bodily from 

 other systems and only secondarily acquire 

 a sexual status. It cannot be expected, there- 

 fore, that all parts of the developing sex 

 complex will be capable at all times of re- 

 sponding harmoniously to experimental con- 

 ditions which are often of necessity rigid 

 and artificial or improperly timed. The rec- 

 ognition of such differences aids in under- 

 standing the variability so frequently en- 

 countered in the reactions of sex structures 

 to hormones, and the importance of such 

 experimental factors as the timing of treat- 

 ment and dosage. 



IV. Experimental Reversal of Sex 



Differentiation in 



the Gonads 



A. BISEXUAL ORGANIZATION OF THE GONAD 



AND THE PHYSIOLOGIC MECHANISM 



OF SEX DIFFERENTI.ATION 



The sexually undifferentiated gonads of 

 most amphibians exhibit bisexual organiza- 

 tion in a primitive and simple form. In 

 early larval life the gonad, irrespective of 

 its future sex, contains two histologically 

 distinct components in which male and fe- 

 male potentialities are segregated. Inter- 

 nally, there is a hilar or centrally placed 



