1002 



SPERM, OVA, AND PREGNANCY 



16.11). Treatment with 2.5 mg. cortisone 

 acetate per day was partially effective in 

 restoring reproductive capacity. Injections 

 of 1.25 mg. hydrocortisone acetate per day 

 gave results comparable with those ob- 

 tained when cortisone was given, although 

 the ratio of young born alive to implanta- 

 tion sites indicated that hydrocortisone 

 acetate was more effective. It was definitely 

 more effective than cortisone acetate in 

 maintaining the body weight of the mother. 

 However, reproduction was completely re- 

 stored to normal in the adrenalectomized 

 rat following treatment with desoxycorti- 

 costerone acetate and cortisone acetate. 



Interference with gestation in the normal 

 animal has been reported by several in- 

 vestigators following treatment with ACTH 

 or adrenal corticoids (Courrier and Co- 

 longe, 1951; Robson and Sharaf, 1952; 

 Velardo, 1957). This is taken to indicate 

 that there is a finely balanced requirement 

 for adrenocortical hormones during gesta- 

 tion ; and that suboptimal or supra-optimal 

 amounts of the hormone interfere with 

 pregnancy. Courrier and Colonge found 

 that cortisone administered to intact rab- 

 bits in the second half of pregnancy inter- 

 fered with gestation. Robson and Sharaf 

 treated both pregnant rabbits and mice 

 with ACTH and reported a marked effect 

 on gestation. Abortion or resorption oc- 

 curred in 8 of 9 mice and in 8 of 11 rabbits. 

 Contamination by posterior pituitary hor- 

 mones or gonadotrophins can be excluded. 

 A subsequent experiment with cortisone 

 also caused marked interference with preg- 

 nancy in the rabbit when 20 mg. were given ; 

 10 mg. were without effect. Administration 

 of cortisone to castrated or hypophysecto- 

 mized pregnant rabbits maintained with 

 progesterone also caused damage to the 

 pregnancy. Since the hormone was not act- 

 ing by way of the ovary or pituitary gland, 

 the authors felt that cortisone was acting 

 directly on the uterus and the uterine con- 

 tents. 



In the rat, however, ]Meunier, Duluc and 

 Mayer (1955) observed an effect on preg- 

 nancy only when cortisone acetate was in- 

 jected at the time of mating. Rats injected 

 with 10 to 25 mg. cortisone acetate daily 



for 5 to 6 days beginning on day 12 or day 

 14 of gestation had a normal pregnancy. 



Velardo (1957) reinvestigated the prob- 

 lem in the rat and reported a marked re- 

 duction in litter size and an increase in the 

 number of stillborn following ACTH treat- 

 ment. Although quantitative differences 

 appeared, a significant decrease in litter 

 size w^as observed only when the hormone 

 was given (1) before mating, (2) immedi- 

 ately after mating, or (3) between the 11th 

 and 15th day after mating. However, the 

 greatest effect was noted when the ACTH 

 was administered immediately after mating. 

 Surprisingly enough, litter size was mark- 

 edly reduced only if adrenalectomy was 

 performed on day 7 of gestation. Adrenalec- 

 tomy on day 8 to 14 of gestation had no 

 effect on live litter size. However, a total 

 of 6, 9, and 13 stillbirths were obtained 

 following adrenalectomy on days 8, 9, and 

 11. It is interesting that the number of still- 

 births decreased from 21 following ad- 

 renalectomy on day 7 to none following ad- 

 renalectomy on day 14. It is apparent that 

 the adverse effects of adrenalectomy on 

 gestation decrease as pregnancy progresses. 

 It is also apparent from these and other 

 experiments that the action of ACTH is 

 mediated by the adrenal cortex. From these 

 results and others described above, it seems 

 likely that the adrenal corticoids may be 

 acting on the uterus. 



Mayer and Duluc (1955) found that 

 adrenalectomy of the I'at on the 14th to 

 the 16th day of pregnancy led to variable 

 results. In 17 pregnant adrenalectomized 

 rats, gestation was terminated in 8, but 

 no interference was observed in 9. The rats 

 that failed to maintain pregnancy died 

 witiiin 2 to 3 days. Again it would appear 

 that delicate hormonal balances are in- 

 volved. In a further investigation of this 

 problem Aschkenasy-Lelu and Aschkenasy 

 ( 1957) reported that a diet adequate in salt 

 and proteins would prevent interference 

 with pregnancy in rats adrenalectomized 

 before mating. On a low protein diet, preg- 

 nancy could be maintained only in the in- 

 tact rat (80 per cent) and then only if 

 daily injections of progesterone were given. 

 These authors believe that the role of the 



