HORMONES IX DIFFERENTIATION OF SEX 



103 



freemartin gonads morphologic transforma- 

 tion may be extreme, although the resulting 

 testis-like structure is histologically abnor- 

 mal and is almost invariably sterile (Wil- 

 lier, 1921 ).» 



2. Bisexual Potentiality in the Embryonic 

 Ovary of the Rat 



One of the best known cases illustrating 

 a well marked capacity for bisexual differ- 

 entiation in a mammalian gonad is provided 

 by the embryonic ovary of the rat. The gon- 

 ads of rat embryos have been isolated at 

 various stages, both before and during the 

 period of histologic differentiation, and 

 transplanted to various locations in adult 

 hosts of both sexes, normal and castrate, 

 beneath the capsule of the kidney (Buyse, 

 1935; Mclntyre, 1956), subcutaneously 

 (Moore and Price, 1942), to the omentum 

 (Holyoke, 1949) and into the anterior cham- 

 ber of the eye (Torrey, 1950). In general, 

 differentiation of the transplanted gonad 

 proceeds without reference to the sex or the 

 hormonal status of the host (certain minor 

 exceptions will be noted later) ; however, 

 there is a great difference in the behavior of 

 testis and ovary after transplantation with 

 respect to their capacity for autonomous 

 differentiation. There is virtual agreement 

 among all investigators that the testis pri- 

 mordium from the beginning of its develop- 

 ment possesses a remarkably stable organi- 

 zation, and develops more or less normally 

 in the various foreign environments, even 

 when isolated before the beginning of histo- 

 logic sex differentiation.^*^ The case of the 

 ovary is entirely different; its organization 

 appears to be extremely labile and it is in- 

 capable of fully autonomous development 

 until a relatively late stage of differentia- 

 tion, after a well formed cortex is present. 

 Before this stage (w^iich according to Tor- 

 rey is reached about the 17th day of devel- 

 opment) ovaries in a high percentage of 

 cases either do not develop at all, or are 



^ For an important exception in which a free- 

 martin testis is well supphed with germ cells and 

 essentially normal in appearance see Hay (1950). 



" Torrey considers that the self-differentiating 

 capacity of the testis probably dates from the lay- 

 ing down of the early gonadal blastema, i.e., the 

 material of the primary sex cords, which occurs as 

 early as the eleventh day of development. 



prone to undergo spontaneous reversal, due 

 apparently to incapacity of the prospective 

 cortical component to develop effectively in 

 abnormal tissue environments. On the other 

 hand, the medullary component of the trans- 

 planted ovary suffers no such handicap and 

 frequently assumes the lead in development. 

 The embryonic ovary of the rat thus pro- 

 vides a flexible system for the study of the 

 morphogenetic capabilities of the cortical 

 and medullary components at different 

 stages of development and under different 

 experimental conditions. 



When transplanted early in development 

 prospective ovaries may give rise (Buyse, 

 1935) to structures of four types: (1) poorly 

 developed grafts of indeterminate sex, (2) 

 atypical ovaries of retarded development, 

 (3) ovotestes in which both sex components 

 are readily identifiable, and (4) rudimen- 

 tary testes. As a group, ovaries are ad- 

 versely affected by transplantation. Some 

 fail entirely to develop the specific struc- 

 ture of gonads (type 1, above) and those 

 that do give rise to ovaries that are greatly 

 retarded (type 2). On the other hand, the 

 medullary component of the prospective 

 ovary resembles the testis in possessing con- 

 siderable powers of self-differentiation. 

 Thus in many cases the two components de- 

 velop together, resulting in an ovotestis; in 

 still others the cortical element fails com- 

 pletely to survive and the medulla alone 

 develops, giving rise to a rudimentary testis. 

 The development of types 3 and 4 is favored 

 by the fact that cortical differentiation is 

 almost always severely repressed. This may 

 have the effect of releasing the medullary 

 element from an inhibition normally im- 

 posed by the dominant cortex. In all cases, 

 however, the phenomenon of reversal was 

 found to be unrelated to the sex of the host] 

 it seems to occur spontaneously, as it were, 

 in consequence of a disturbance in the nor- 

 mal balance between cortical and medullary 

 systems. 



A similar behavior is seen wdien entire re- 

 productive tracts of rat embryos, including 

 the gonads, are transplanted subcutaneously 

 into hosts of various ages, male or female, 

 and into castrate hosts of both sexes (Moore 

 and Price, 1942). Again it was found thai 

 the sex or the hormonal status of the host 

 has no apparent influence on the result. 



