118 



BIOLOGIC BASIS OF SEX 



spectively. Similar behavior is seen in grafts 

 to the eye chamber of castrate hosts (the 

 guinea pig, Bronski, 1950) and after trans- 

 plantation of the entire embryonic genital 

 tract into castrate and noncastrate hosts of 

 various ages (the rat, Moore and Price, 

 1942). Although the experimental environ- 

 ments in all of these cases cannot be con- 

 sidered hormone-free in the strict sense 

 (Jost and Bozic, 1951), the results indicate 

 that the development of the female sex ducts 

 when removed from the influence of the em- 

 bryonic testis is a matter of autonomous 

 differentiation. 



The above experiments show that in rat 

 embryos the fate of the JMlillerian ducts 

 is undetermined up to an age of 16 to 17 

 days at least (Jost and Bozic), since at this 

 age these ducts in male embryos still retain 

 their capacity for autonomous development 

 when removed from the inhibiting influence 

 of the testis. Experiments on the same spe- 

 cies (Price, 1956; Price and Pannabecker, 

 1956 1 indicate that involution is irreversibly 

 determined at about the age of 17 days. The 

 genital tracts of male fetuses were removed 

 at 17.5 days of gestation and cultured in 

 vitro. At this stage the first signs of involu- 

 tion can be detected in the region of the 

 ostium but the posterior extremities of the 

 ducts are still growing. After explantation 

 the ducts continue to regress regardless of 

 whether the testes are included in the ex- 

 plant or not, whereas those of female fetuses 

 under the same conditions develop nor- 

 mally. It seems that the fate of the Miil- 

 lerian ducts in the male becomes irre- 

 versibly fixed within the brief period of a 

 day by exposure to the testis hormone. 



This question has })een investigated in 

 some detail in the chick. It had been shown 

 earlici- that after transplantation to the 

 cliurioalhintois, Miillerian ducts from em- 

 bryos of either sex differentiate completely 

 if isolated before the beginning of sex dif- 

 ferentiation. But if transplanted later than 

 the 10th day of incubation the ducts of male 

 embryos invariably degenerate; beyond tliis 

 age their involution has been finally de- 

 termined (Wolff and Ostertag, 1949). Mak- 

 ing use of the technique of culture in vitro 

 the analysis has been carried fartliei' (Wolff 

 and Lutz-Ostertag, 1952). When isolated 



before the appearance of sex differentiation 

 in the gonads, again the Miillerian ducts of 

 both sexes undergo a complete differentia- 

 tion, as in castrate embryos; but if isolated 

 after the 9th day the ducts of male em- 

 Ijryos i^romptly undergo involution. How- 

 ever, if the Miillerian ducts of female em- 

 bryos are cultured in the presence of an 

 embryonic testis, a typical involution takes 

 place (although at the same time the ad- 

 jacent Wolffian ducts develop normally). 

 Furthermore, when testosterone propionate 

 is added to the medium it has the same effect 

 as the embryonic testis (Wolff, Lutz-Oster- 

 tag and Haffen, 1952; for a summary see 

 Wolff, 1953b). These results hardly leave 

 the role of the male hormone in doubt. It 

 follows also that the action of the hormone 

 in vitro must be direct. Evidence has been 

 obtained to show that the process of involu- 

 tion of the ducts is of the nature of an 

 autolysis produced by the action of pro- 

 teolytic enzymes which are presumabh' ac- 

 tivated l)v the male hormone (Wolff, 

 1953b). 



Summary and conclusions. On the basis 

 of present knowledge, the following gen- 

 eral statements may be made concerning 

 the role of sex hormones in the differentia- 

 tion of the Miillerian ducts. 



a. Female hormone, in most species, stim- 

 ulates precocious growth and development 

 of the Miillerian ducts and their derivative 

 structures in embryos of either sex when 

 given in adequate dosages. Administered 

 at an early stage it prevents the normal in- 

 volution of the ducts in male embryos after 

 which development may continue without 

 further treatment. In certain mammalian 

 species, however (hamster, field mouse, 

 man), negative results have been reported, 

 which may possibly be related to the level 

 of estrogen prevalent during gestation in 

 these species or to dosage. 



b. Male hormone, if administered early, 

 has an inliibitory action on the Miillerian 

 ducts in the embryos of birds and am- 

 phibians. In some species the primary de- 

 \-el()l>nient of the duct is entirely suppressed; 

 in other cases only a partial inhibition oc- 

 curs. In mammals, the hormone of the em- 

 bryonic testis ]M-o(lnccs involution of the 

 (hicts in males at tlic beginning of sex dif- 



