MAMMALIAN OVARY 



451 



lar to those in intact cycling animals are 

 being evoked, no satisfactory conceptualiza- 

 tion of ovarian functioning will be possible. 



Chorionic gonadotrophins are not with- 

 out practical value in the stimulation of 

 ovulation (Cole and Miller, 1933; Folley 

 and Malpress, 1944; Folley, Greenbaum 

 and Roy, 1949; Marden, 1951; Umbaugh, 

 1951; Robinson, 1954; and others); never- 

 theless, their contribution to ovarian physi- 

 ology may be limited. Bradbury has pointed 

 out in a personal communication that the 

 human placental hormone (HCG) is exotic 

 for laboratory animals. It has practically 

 no effect on the ovaries of guinea pigs or 

 field mice. In rats its biologic effects arc 

 finite different from those of pituitary lu- 

 teinizing hormone (LH) or interstitial cell- 

 stimulating hormone (ICSH) (Selye, Collip 

 and Thomson, 1935; Evans, Simpson, Tolks- 

 dorf and Jensen, 19391. HCG is so ineffec- 

 tive in the hypophysectomized rat that it 

 has been assumed, in the case of the intact 

 animal, either that it acts through the pitui- 

 tary or that it requires the presence of the 

 pituitary to be effective (Aschheim, Fortes 

 and Mayer, 1939; Noble, Rowlands, War- 

 wick and Williams, 1939) . If HCG and other 

 chorionic gonadotrojihins are exotic, as such 

 results would indicate, the extrapolation of 

 effects which have followed their use to the 

 normal functioning of the ovary could be 

 seriously misleading. 



What we have written is intended to set 

 the tone for what follows. Many of the solid 

 accomplishments of the past two decades 

 will be recounted, but the areas of uncer- 

 tainty and the difficulties which slowed 

 down the progress of the twenties and thir- 

 ties will be enumerated in the hope that 

 the curiosity of a new generation will be 

 aroused and guide us into a period of even 

 more productive eft'ort. 



II. Folliculogenesis 



A. GROWTH OF PRIMARY AND SM.\LL 

 VESICULAR FOLLICLES 



In mammals, by the time of birth, oogonia 

 have completed their proliferative activity 

 and become primary oocytes. The serosal 

 surface of the ovary is covered by a layer 

 of cells known as the germinal epithelium. 

 There has been and still is considerable 



speculation whether adult germinal epithe- 

 lium contains, or gives rise to, any germ 

 cells (Sneider, 1940; Mandl and Zuckerman, 

 1950, 1951a-d, 1952b; Zuckerman, 1951; 

 Green and Zuckerman, 1951). The subject 

 is reviewed extensively by Brambell ( 1956 ) 

 and in the chapter by Blandau. Careful 

 studies of human ovaries have been made 

 by Block (1951a, b, 1952, 1953). From all 

 this material, it is clear that a satisfactory 

 answer has not been given. The latter may 

 be awaiting the development of a fresh ap- 

 proach and until then another review of the 

 many conflicting reports and opinions would 

 be repetitious. 



]\Iore relevant to the present review is 

 the relationship between ovarian estrogens, 

 on the one hand, and germ cell proliferation 

 and follicle development, on the other. It 

 has been claimed that exogenous estrogen 

 stimulates mitotic activity in the germinal 

 epithelium in mice, rats, and the minnow, 

 Phoximis laevis L. (Bullough, 1942a, 1943; 

 Stein and Allen, 1942; de Wit, 1953; von 

 Burkl, Kellner, Lindner and Springer, 1954) . 

 Bullough (1943) suggested that new cycles 

 of oogenesis are intiated by estrogen in the 

 follicular fluid of large and rupturing fol- 

 licles. Mandl and Zuckerman (1950) and 

 Dornfeld and Berrian (1951) were less cer- 

 tain. The former expressed the belief that 

 the direct effect of estrogenic stimulation 

 cannot be measured by comparing the total 

 number of oocytes in the ovary. The latter, 

 after finding that isotonic saline, gelatine, 

 or agar injected into the perovarian capsules 

 of immature rats elicited mitoses in the 

 germinal epithelium, concluded that the re- 

 action was in response to injury rather than 

 to the substance injected. Notwithstanding 

 the precautionary notes sounded by ]\Iandl 

 and Zuckerman and by Dornfeld and Ber- 

 rian, the number of reports of increased 

 mitotic activity near the site of ovulation 

 or when estrogen is placed in contact with 

 the germinal epithelium remains impressive. 

 Particularly because of the analogy with 

 the androgenic control of spermatogenesis 

 pointed out by Bullough ( 1942b) and others, 

 the possibility should be tested further. 



As the oocyte starts to grow, the flat in- 

 vesting cells proliferate and form the mem- 

 brana granulosa. By the time the rat oocyte 

 has completed its growth it has acciuired 



