966 



SPERM, OVA, AND PREGNANCY 



throughout pregnancy, especially in the 

 second half (Fig. 16.3). 



The discovery by Hooker and Forbes 

 (1947) of a new assay for progesterone 

 sensitive to a concentration of 0.3 /^g. per 

 ml. led to many studies on the blood levels 

 of this hormone during gestation. Subse- 

 quent studies revealed a lack of specificity 

 for the assay (Zarrow, Neher, Lazo-Wasem 

 and Salhanick, 1957; Zander, Forbes, von 

 Miinstermann and Neher, 1958) and a dis- 

 crepancy between the values obtained by 

 chemical and biologic techniques. It is ob- 

 vious that the bioassay data possess signif- 

 icance but a final evaluation can be made 

 only when the identity of the compound or 

 compounds measured in the blood of the 

 animals by the Hooker-Forbes test has been 

 established. 



The concentration of gestagen in the 

 blood of pregnant sheep (Neher and Zar- 

 row, 1954) , women (Forbes, 1951 ; Schultz, 

 1953; Fujii, Hoshino, Aoki and Yao, 1956), 

 rabbits (Zarrow and Neher, 1955), and 

 mice (Forbes and Hooker, 1957) has been 

 determined by the Hooker-Forbes test and 



Fig. 16.3. Urinary excretion of estrogens and 

 pregnanediol throughout gestation in the human 

 being. (From E. Venning, Macy Foundation, Con- 

 ferences on Gestation, 3, 1957.) 



expressed as /^g. equivalents of progester- 

 one. The data obtained from pregnant 

 women by the different investigators are 

 in marked disagreement. Whereas both 

 Forbes (1951) and Schultz (1953) failed 

 to observe any significant rise in blood ges- 

 tation of pregnant women throughout ges- 

 tation, Fujii, Hoshino, Aoki and Yao 

 (1956) obtained a conspicuous rise during 

 this period. The data reported by Forbes 

 (1951) indicate an extremely low level for 

 protein-bound progesterone (0.5 /^g. per 

 ml. plasma or less) and a maximum of 2 

 /xg. per ml. free progesterone (Fig. 16.4). The 

 concentration of the hormone in the blood 

 showed a series of irregular peaks through- 

 out gestation and varied from less than 

 0.3 /xg. to 2 /xg. per ml. plasma. In general, 

 these results were confirmed by Schultz 

 (1953) who assayed the blood from 46 

 women at 6 to 17 weeks of pregnancy. 

 Again the results failed to reveal any con- 

 sistent change with the length of preg- 

 nancy. Both investigators (Forbes, 1951; 

 Schultz, 1953) were led to question the 

 importance of progesterone during gesta- 

 tion in the primate. Fujii, Hoshino, Aoki 

 and Yao (1956), on the other hand, re- 

 ported a significant increase in the level of 

 circulating progesterone throughout ges- 

 tation. Again these investigators used the 

 Hooker-Forbes assay but indicated that 

 the plasma was not treated in any way 

 except for dilution before the assay. The 

 results obtained by this latter group re- 

 vealed a rise from a level of 6 /*g. pro- 

 gesterone per ml. plasma during the luteal 

 phase of the cycle to a high of 25 /i,g. during: 

 the last trimester of pregnancy (Fig. 16.5). 

 The concentration showed a steady increase 

 from the 4th to the 24th week of pregnancy,, 

 and a plateau from the 24th week until 

 term. A sharp drop occurred within 12 to 

 24 hours after parturition with zero values 

 noted by 72 hours postpartum. Analysis of 

 the urine for pregnanediol showed a rather 

 good correlation between the two curves al- 

 though the plasma levels rose sooner than 

 the urinary pregnanediol. 



The curve for the concentration of pro- 

 gesterone in the pregnant mouse is 

 markedly different from those reported for 

 other species (Forbes and Hooker, 1957). 

 Again the Hooker-Forbes assay was used 



