SEXUAL RESPONSIVENESX AND TENPORALLY RE- LATED PHYSIOLOGICAL EVENTS DURING

PREGNANCY I N THE RHESUS MONKEY

JOSEPHINE BALL The Henry Phipps Psychiatric Clinic and Carnegie Laboratory of Enzbryo7ogy,

Johns Hopkins Medical School

ONE FIGURE

In connection with the investigations in the embryology and the physiology of reproduction being carried on at the Carnegie Laboratory of Embryology, the writer has been privileged to study the sex behavior of rhesus macaques whose physiological condition is being followed. It is the purpose of this paper to report the findings on three of these animals which became pregnant during the observations and to corre- late quantitative changes in sexual responsiveness with certain anatomical and hormonal events which have been worked out by other members of the staff.

The method of measuring responsiveness was the same as that used in the study of cyclic changes in the normal, non- pregnant animal (Ball and Hartman, '35). It is a measure not of acceptance but of invitation. I n this papcr we showed that, while the female monkey may accept the male at any time in the menstrual cycle, there is, typically, a definite increase in SCX interest around the middle of the cycle just before ovulation.

I n figure 1 similar curves are given for a menstrual cycle of three females, the curves being continued into pregnancy. It will be seen that one of these animals was observed throngh- out pregnancy, one was surgically aborted on the sixty-ninth day of gestation and the third suffered spontaneous abortion on about the seventy-sixth day.

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These curves indicate that sex interest drops after the rise before fertile ovulation, as in the non-pregnant cycle, to rise again 3 to 4 weeks later, almost as if conception had not taken

t SEXUAL RESPONSIVENESS

PREGNANCY BEFORC AND DURING

- BEHAVIOR SCORE

VAGINAL D E SQ UA MAT 10 N ...* .. .. 0 . .

GFSTATION 172 DAYS

PLACENTAL b l C N BLELDIN6 PATHOLOGICAL BLEEDING5

Figure 1

place. This rise occurs soon after the beginning of the bleed- ing of pregnancy or 'placental sign' (Hartman, '29). After this, sex interest disappears, more or less gradually, and the animal remains quite indifferent to the presence of the male

SEXUAL RESPONSIVEKESS I N PREGNANCY 509

throughout the rest of a normal pregnancy. The variation from this shown by female no. 57, who aborted spontaneously, will be discussed below.

While this record of the macaque's sex behavior during pregnancy is a matter of some interest. per se, it acquires somewhat greater significance when temporally correlated with certain other physiological processes, namely, the em- bedding of the egg, the excretion of prolan, involution of the corpus luteum, regression of the vaginal mucosa.

Unpublished data which are being gathered by Dr. G. L. Streeter and Dr. G. B. Wislocki (to be published in the Contributions to Embryology, Carnegie Institution of Wash- ington publications) show that the attachment of the ovum to the uterine wall begins, in the monkey, between the ninth and tenth days after fertilization. The epithelium proliferates and is apparently ingested by the trophoblast. This process reaches its height at the fifteenth to sixteenth day, which is about the time the kidney begins to excrete the anterior pitui- tary-like substance (prolan) as has been found recently by Dr. G. W. D. Hamlett ( '37).

By the twenty-fifth day of gestation the embryo has estab- lished the relation to the maternal structures which it main- tains throughout the rest of pregnancy, obtaining its nourish- ment henceforth, not by direct ingestion of maternal tissue but by means of its now established circulatory system through the walls of the villi which have been developing from the sixteenth to the twenty-fifth days. It is on about the twenty- fifth day also that prolan practically disappears from the urine (Hamlett, ' 37 ) , not to reappear in detectable quantities during the rest of gestation (Allen, Maddux and Kennedy, '31; Snyder and Wislocki, '31). This is also the date de- termined by Corner, Rartelmez and Hartnian ('36) wlien the corpus luteum of pregnancy undergoes certain regressive changes.

Behavioral phenomena and the vaginal pictures are not so definitely timcd and they seem t o partake more of the nature of continuance of a cyclic tendency similar to that described

510 JOSEPHINE BALL

in the pregnant chimpanzee by Tinkelpaugli ('33) and by Scliultz and Snyder ( ' 3 5 ) than to be an integral part of gestation, as are the events described in the last two para- graphs. There may or may not, therefore, be some signifi- cance in the fact that the peak of sexual responsivness comes hetween the sixteenth and tweuty-fifth days. But it is cer- tainly significant that this cyclic tendency is pretty definitely repressed after the twenty-fifth day when the primarily gesta- tional processes have settled into their final form.

With reference to the changes in the vaginal mucosa, Hartman ( ' 3 2 ) has described the continuation of cycles of desquamation in the first part of pregnancy. Usually there is a single rise after the one accompanying conception, cor- responding roughly to the rise in sexual responsiveness. Occasionally there is a second wave and sometimes no rise at all. Desquamation in the three animals under discussion in this paper is shown by the dotted lines in figure 1, in per cents of sediment in the vaginal lavage (compare Hartman, '32). Female no. 2 had a second rise almost as high, if not so pro- longed, as the first one. It will be noted that there is a sug- gestion of a rise also in sex interest. Possibly there would be cases of more definite irregularities in behavior as in desquamation had more cases been studied. Female no. 57, of course, constitutes a special case.

After the cycle or cycles of early pregnancy there is a pro- gressive atrophy of the vaginal mucosa until, by the one- hundredth day of gestation, its condition resembles that of the castrate (Allen, '27; Davis and Hartman, '35), in which state copulation often causes bleeding (observations by the writer, to be published elsewhere).

The facts presented in this paper are insufficient for profitable speculation on the endocrinological significance of these temporally associated events. However, they make it evident that the first month of pregnancy is one of complex shifting of the endocrine controls, with a fairly abrupt settling into the organization that continues, apparently with relative stability, throughout the rest of the 5 months of gesta- tion, aathough in some cases there may be one more wave of

SEXUAL RESPONSIVENESS I N PREGNANCY 511

desquamation and possibly of sex interest after this first month.

With regard to the special case of female no. 5'7, there seems to be evidence in her curves of vaginal desquamation and of sexual responsiveness that this abortion was due to some sort of failure of balance in the endocrine complex that should control pregnancy, since there was a rise of sex interest be- fore and an increase of desquamation before and after the probable date of abortion which was determined by palpation by Dr. C. G. Hartman. The stimulation of the vaginal mucosa of castrate monkeys has been described by Allen ('27) and by Davis and Hartman ( ' 35 ) . Increased sexual responsiveness has also been induced in castrated female monkeys by estrin injection (Ball, '36). These facts suggest that the abortion was due to an endocrine imbalance characterized by too much estrin. Because of the recognized antagonism between estrin and progestin, it is interesting to refer here also to the paper by Snyder ('34) who showed that parturition fails to occur in the rabbit until termination of the life of the corpus luteum, even when, by the induction of a fresh set of corpora lutea, gestation is prolonged to the point of uterine injury due to postmature fetuses. None of these facts, however, offer any clue to what started the endocrine imbalance that was the apparent cause of this abortion.

SUMMARY

Quantitative changes in sexual responsiveness which the writer has found in three pregnant rhesus monkeys are temporally correlated with other indicators of endocrine changes and with uterine events as they have been determined by various investigators in the Carnegie Laboratory of Embryology. The findings indicate that there is a complex shifting of endocrine controls throughout the first month of pregnancy while the embryo is establishing its relation to the maternal organism, with some tendency to continuance of cycles in behavior and vaginal desquamation.

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I n one case, spontaneous abortion was associated with a definite continuation of these cycles f o r 2 months after con- ception, indicating a failure of the endocrine mechanism which normally maintains pregnancy.

LITERATURE CITED

ALLEX, E. 1927 The nienstrual cycle of the monkey Macacus rhcsus. Contrib. Embryol. no. 98, Carnegie Institution of Washington, Pub. no. 380,

ALLEN, E., W. P. R f ~ n ~ u x AND J. W. KENNEDY 1931 Ovarian and anterior pituitary hormones from the pregnant monkey. Proc. Soc. Exp. Biol., vol. 28, p. 403.

BALL, J. 1936 Sexual responsiveness in female monkeys after castration and subsequent estrin administration. Psychol. Bull., vol. 33, p. 811.

BALL, J. AND C. G. HAXTIVIAN 1935 Sexual excitability as related to the menstrual cycle in the monkey. Am. J. Obst. and Gyn., vol. 29, p. 117.

CORNER, G. W., WITEI THE COLLABORATION OF G. w. BARTELMEZ AND C. G. XIARTMAN

1936 On normal and aberrant corpora lutea of the rhesus monkey. Am. J. Anat., vol. 59, pp. 433-457.

Changes in vaginal epithelium during pregnancy in relation to the vaginal cycle. J. Am. Med. Assoc.,

Positive Friedman tests i n the pregnant rhesus monkey, Macaea mulatta. Am. J. Physiol., vol. 118, April.

Uterine bleeding as an early sign of pregnancy in the monkey (Maeacus rhesus), together with observations on the fertile period of the menstrual cycle. Bull. Jolins Hopkins Hosp., vol. 44,

Studies in the reproduction of the monkey Macacus (pithecus) rhesus, with special reference t o menstruation and pregnancy. Contrib. Embryol. no. 134, Carnegie Institution of Washington Pub. no. 433,

Observations on reproduction in the chimpanzee. Bull. Johns Hopkiris Hosp., vol. 57, pp. 193-205.

The prolongation of pregnancy and complications of par- turition in the rabbit following induction of ovulation near term. Bull. Johns IIopkins Hosp., vol. 54, pp. 1-23.

The effect of the injection of urine from pregnant mammals on ovulation in the rabbit. Bull. Johns Hopkins Hosp., vol. 48, pp. 362-367.

Sex rycles and other ryclic phenomena in a chimpan- zee during adolescence, maturity and pregnancy. J. Morph., vol. 54,

V O ~ . 19, pp. 1-44.

DAVIS, M. E. AND C. G. HARTMAN 1935

V O ~ . 104, pp. 279-285. HAMLETT, G. W. D.

HARTMAN, C. G. 1929

1937

pp. 155-164. 1932

V O ~ . 23, pp. 1-161. SCHCLTZ, A. H. AND F. F. SNYDER 1935

SNYDER, F. F. 1934

SNYDER, F. F. AND G. B. WISLWKI 1931

TINKELPAUGH, 0. L. 1933

pp. 521-547.