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THE MENSTRUAL CYCLE OF THE PRIMATES. PART VII.
THE SEXUAL SKIN OF THE CHIMPANZEE

By S. ZUCKERMAN! anv J. F. FULTON

From the Department of Physiology, Yale University School of Medicine

I. INTRODUCTION

Uverine bleeding, recurring in approximately thirty-day periods, is a
physiological characteristic of Old World Primates. As part of their generative
mechanisms, many animals falling in this group also display cyclical variations
in the swelling and coloration of the external genitalia and of the neighbouring
skin, the total area affected in this way usually being referred to as the “sexual
skin.” The systematic distribution of sexual-skin changes was discussed in the
first part of this series of papers (Zuckerman, 1930); in view of the fact that the
sexual skin of the rhesus macaque (Macaca mulatta) had been shown to be controlled by the follicular hormone “‘oestrin” (Allen, 1927), and in virtue of the
approximate similarity in the time relations of the changes throughout the Old
World group of Primates, it was there suggested that oestrin probably constitutes the controlling endocrine mechanism of the sexual skin, wherever such
a skin occurs and in spite of its morphological variations. This generalisation
was later borne out in the case of the baboon (Parkes and Zuckerman, 1931)
and in that of the mangabey (van Wagenen, 1932). An experiment is reported
in the present paper indicating that oestrin also activates the sexual skin of the
chimpanzee.

Il. THE EXPERIMENTAL ANIMAL

The animal studied was an adolescent chimpanzee (Pan satyrus), which had
been captured in French Guinea in January 1930. She was brought to the
United States of America soon afterwards, and lived for some three years in
the Yale Laboratory of Comparative Psychobiology under the name of “ Kani.”
According to criteria followed in that laboratory, the animal’s birth-date was
estimated to have been 1926. At the time of her use in the present experiment,
all of her permanent teeth except the third molars had erupted. Only about
two-thirds of the canines were through the gums. A similar dental formula in
European children is as a rule characteristic of the age of 12. According to
current views it is representative of an age of about 8 in chimpanzees—a figure
which tallies with the earlier estimate of Kani’s year of birth.

1 At the time of the investigation, a Rockefeller Research Fellow in the Department of
Physiology, Yale University School of Medicine.
The Menstrual Cycle of the Primates 39

A record of the animal’s “menstrual history”’ has been kept in the laboratory’s routine protocols, and the following brief account is taken from this
source.

Menstruation. There is no record that the animal ever menstruated. A
janitor reported “genital bleeding” on 9 October, 1931, but the observation
was not confirmed by any member of the research staff of the laboratory, nor
was a similar observation ever again made. It is likely that the blood seen was
a memento of a fight, since there is a record of the animal's temporary unfriendly relations with two cage companions.

Sexual skin. The first definite swelling and reddening of the genital region
was noted on 26 July, 1932. From this time until the day she was used in the
present experiment, fourteen months later, the animal experienced cycles of
sexual-skin activity. These do not appear to have been regular, and sometimes
swelling continued for long periods, fluctuating in amount from time to time.
The amount of swelling was never much more than that indicated in the photograph reproduced in text-fig. 1 (according to Dr K. W. Spence, who had charge
of the animal for a considerable time, the swelling shown in this picture is about
three-quarters the maximum she ever exhibited), and because of the narrow
range of fluctuation, it was usually impossible to judge the exact onset, the
maximum, or the beginning of decline, of the swelling. This record would
indicate that Kani was still immature at the time she was used in the experiment reported here, since the swelling she experienced was no more than that
shown by chimpanzees passing through puberty. The swelling of the adult
chimpanzee is considerably greater (see Tinklepaugh, 1933, for figures); the
amount shown may vary from one mature individual to another, but the adult
minimum of full swelling is several times that shown in text-fig. 1.

Tinklepaugh (1933) has recently published an account of a chimpanzee’s
puberty and maturity. The history of his animal, Dwina, is very unlike that of
Kani. In its first cycle of activity, Dwina’s sexual skin expanded until it was
half the size of her head. Even after a year of recurring periods of swelling,
Kani’s sexual skin never became as big—judging by Dr Spence’s statement.
The interval between recurring sexual-skin swellings varied in Dwina from 32
to 86 days. There was no regular periodicity in Kani’s sexual-skin swellings.
Dwina menstruated within 5 months and conceived within 9 months of her
first cycle of swelling. Kani showed no signs of menstruation during a year of
sexual skin cycles.

These differences are pointed out here, as they indicate that Kani’s
puberty was a very protracted process. Such long-drawn puberties are not
uncommon among the Old World and subhuman Primates generally. In an
earlier paper (Zuckerman, 1930) one of us has drawn attention to this fact and
remarked on a chimpanzee (S), under observation in the London Zoological
Gardens, in whom an interval of approximately two years intervened between
the first swelling of the sexual skin and the first menstruation. The protracted
puberty of monkeys has since been discussed by Hartman (1981).
40 S. Zuckerman and J. F. Fulton

Temperamental changes connected with the process of Kani’s reproductive
maturation. Kani was under investigation by Dr Spence in a study of visual
acuity. He found that Kani was more irritable, and that the level of her attention became considerably reduced, during periods of swelling. At these times
she made more errors in her tests, thus raising the threshold of her visual
responses (Spence, 1934).

General condition. Kani was more or less totally blind when she became
available for the present experiment. Her left occipital lobe had been extirpated by one of us (J. F. F.) on 24 May, 1933, and the lateral surface of the right
occipital lobe was removed on 7 July.

 

Text-fig. 1. Photograph of experimentally induced sexual-skin swelling
in a chimpanzee.

About the middle of August the animal began to be affected by diarrhoea
which persisted until her autopsy on 28 October. Throughout these last weeks
of her life she wasted considerably, a fact to which the following body-weight
figures lend eloquent testimony:

May 24 ... wee .. 85 kg.
September 29... ... 22-7 kg.
October 28 .. . ctrca 17 kg.

There is no record of any sexual-skin swelling between the end of July and
29 September, when the animal’s ovaries were removed.
The Menstrual Cycle of the Primates 4]

III. EXPERIMENTAL RESULTS

The original plan had been to observe not only the chimpanzee’s reaction to
injections of oestrin, but also to discover whether or not uterine bleeding
follows ovariectomy in the chimpanzee in the same way as in the rhesus
monkey. The latter part of the plan had to be abandoned because of the animal’s
poor condition. Oestrin injections were begun too soon after the removal of
the ovaries to allow of any definite answer to the question.

The ovaries were removed, under sodium amytal anaesthesia, on 29 September, 19338. They were equal in size, and mottled with small follicles, the
largest visible being 8-4 mm. in diameter.

The right ovary was immediately fixed in Fleming’s strong solution; the
left, which was fixed in Bouin’s solution, measured when fresh 2-7 cm. in
length, 1-5 em. in width, and 1-0 cm. in thickness, and weighed 1-:1960 gm.
Both ovaries were serially sectioned, and histologically there is practically no
difference between the two. The cortex contains many follicles, but in the stained
preparations none is larger than 2 mm. in diameter. Most follicles of this size
(as well as some so small that an antrum had not yet appeared) are in process of
atresia, and no luteal tissue is present anywhere to indicate that follicular
growth had ever proceeded beyond this stage, or that ovulation had ever
occurred. Wide blood spaces are present in the granulosa of some of the larger
follicles undergoing atresia. The peripheral zone of the ovary is extremely
rich in primordial follicles.

The uterus was fairly large, but flabby, and was lying in a retroverted
position, the fundus well to the right.

The wound healed by first intention, but Kani’s general condition became
steadily worse. Diarrhoea varied in intensity from day to day, as did also the
animal’s responsiveness and general activity. The process of emaciation continued evenly until the day of the autopsy (28 October). The animal’s prostrate
condition on this day represented a very sudden turn for the worse, and it was
on this account that the experiment was summarily ended.

Injections of oestrin. These were begun on 9 October, ten days after the
removal of the ovaries. The preparations used were concentrated oily solutions
prepared by Parke Davis and Co. and by the Schering Corporation (the product
of the latter firm going under the name of “Progynon”). Owing to the difficulty of restraining the animal, daily injections were not given until a week
after the beginning of the course of injections, when the animal had ceased to
resist being restrained. Injections were given both subcutaneously and intramuscularly, and only once daily (except one day towards the close of the series,
when two injections were made). The course lasted twenty days, the last
injection being given about an hour before the autopsy. Disregarding this
final dose, 21,100 r.u. of oestrin, according to the manufacturers’ assay, were
injected into the animal.

The vaginal smear and uterine bleeding. At no time was there any bleeding
42 S. Zuckerman and J. F. Fulton

from the vagina, and red blood corpuscles were never seen in preparations of
the vaginal lavage. Leucocytes predominated at the time of the ovariectomy,
and epithelial elements during the course of injections.

The sexual skin. At the time of the ovariectomy, and at the beginning of
the course of injections, there was no swelling of the vulval area, which did not
protrude beyond the level of the ischial tuberosities.

The first sign of swelling was noticed on 12 October, three days following the
first injection, after 3000 r.u. had been given. On the 7th day (7000 Rr.v.), the
swelling was about as conspicuous as that indicated in text-fig. 1, and could be
differentiated into a more prominent tense vulval and circumanal part, and a
slacker base formed by the swollen pigmented surrounding skin. The amount of
swelling fluctuated somewhat from this time on, and the maximum of the
experiment was recorded on the 15th day of injections (16,000 r.u.). Although
bigger on this day, the sexual skin was less tense than it had been at the
beginning of its phase of swelling, and in the succeeding five days it also decreased slightly in size—in spite of the further injection of 5000 r.u. All this
time, as noted previously, the animal was suffering from severe diarrhoea. The
photograph of text-fig. 1 was taken on the 19th day of injections (the day before
the autopsy), and it does not show the maximum of swelling attained.

At no time was the swelling greater than that characteristic of puberty.

Autopsy and histological notes. The animal was killed with an injection of
dial supplemented by an overdose of ether on 28 October. There were numerous
peritoneal adhesions and the large intestine was considerably inflamed, this
finding presumably accounting for the severe and persistent diarrhoea.

The internal and external generative organs were removed in one piece,
and dropped without further dissection into Bouin’s picric-formol. Unfortunately penetration was slow and the fixation proved to be poor.

The uterus. At the autopsy the uterus appeared to be bigger than it was at
the time of the removal of the ovaries. This increased size was not obvious in
the fixed specimen, which had the following dimensions:

Fundus-cervix length... wee ... 50mm.
Greatest width at fundus wee ... 80mm.
Greatest thickness at fundus ... ... 20mm.

The histological appearance of the uterus is very unusual. It is that of a
uterus in a condition of advanced endometrial hyperplasia, the endometrial
overgrowth presumably having been occasioned by the injections of oestrin
(see Plate I, fig. 1. Plate I, fig. 2 is a photomicrograph of a control uterus,
removed at autopsy from a chimpanzee of slightly younger dental age; except
that the number of 2 mm. follicles were fewer, the ovaries of this ‘“‘control”’
animal were almost the same in appearance as those of Kani). A detailed
description of the specimen has been given elsewhere (Zuckerman and Morse,
1984).

The vagina. (Plate I, fig. 3.) The sections show the usual effects of oestrin
The Menstrual Cycle of the Primates 43

upon the vagina. The epithelium is thick and differentiated into a superficial
keratinised zone and a deeper and narrower darkly staining zone.

The sexual skin. (Plate I, fig. 4.) The blocks of tissue studied were so
removed as to include the external surface of the swelling, and they show the
superficial keratinisation which generally characterises the follicular phase of
sexual-skin swelling (e.g. in the baboon, Zuckerman and Parkes, 1932). The
vessels are moderately dilated in the deeper zones, and the nuclei are fairly
widely dispersed, as in the full swelling of the baboon and in the pubertal
sexual-skin swellings of the rhesus monkey, but the collagenous connective
tissue is denser than in either of these two other primate forms. This denser
appearance of the connective tissue, which may be taken toimply a lesser degree
of intercellular oedema, is an indication of the relatively small amount of
swelling that was induced by the oestrin injections.

IV. DISCUSSION

The experiment clearly indicates that oestrin activates the sexual skin of
the chimpanzee. It is, however, difficult to understand why a dose of the hormone as large as 22,000 R.U. failed to produce more swelling than it actually did.
80,000 m.vu. of oestrin were necessary to produce full swelling in the baboon
(Parkes and Zuckerman, 1981), and this amount on any conservative estimate
of the relation of mouse to rat units could hardly have been more than that
given the chimpanzee. Smaller doses are also effective in the baboon. According to Schoeller, Dohrn and Hohlweg (1933), complete swelling can be produced
in the baboon by 6000-8000 R.v. of oestrin when given by mouth, or 2000 R.u.
when injected intramuscularly (these investigators used the same preparation,
Progynon, as was used on the chimpanzee). Full swelling in the baboon is
much greater than the swelling shown by the chimpanzee of the present experiment. Full or nearly full sexual-skin swelling can be achieved in the mangabey
with amounts of oestrin in the neighbourhood of 7000 R.u. (van Wagenen and
Zuckerman, 1983)—and even smaller doses are effective in this animal. Full
swelling in the adult mangabey, in actual volume, can be little less than the
amount of swelling shown by Kani in this experiment.

Schoeller and his co-workers have shown that in the administration of a
given and constant number of rat units of oestrin to a baboon, the sexual-skin
response varies according to the strengths and spacing of the separate doses. It
is therefore possible that in the experiment with the chimpanzee the injections
were spread over too long a time, and that better effects would have been
achieved in a shorter course of injections and with bigger doses of oestrin than
a maximum of 2000 R.v. a day. Another possible explanation of the small
swelling is the fact that the localising process of oedema, which activity of the
sexual skin appears to represent in large part, was contending in the experimental animal with the dehydrating effect of constant severe diarrhoea. It is
unlikely that part of the explanation of the small amount of swelling lies in the
44 S. Zuckerman and J. F. Fulton

fact that the animal’s sexual skin had never swollen under natural conditions
beyond the point achieved experimentally. Oestrin can produce enormous
swelling in immature rhesus monkeys which have never shown natural sexualskin swelling.
The manner in which the sexual-skin swelling developed in the experimental
chimpanzee has bearings on the morphological homologies of the external
genitalia in mature females of this species of ape. Text-fig. 2 is an accurate

LABIUM
MAJUS

   

PRAEPUTIUM - Stag
CLITORIDIS GLANS CLITORIDIS

RIMA PUDENDI

Text-fig. 2. External genitalia of immature female chimpanzee.

representation of the anterior sexual-skin area of the control chimpanzee whose
uterus is shown in Plate I, fig. 2. At the time of her death this control animal
did not manifest any sexual-skin swelling. A prominent midline groove in front
of the praeputium clitoridis divides the hair-bearing area anterior and lateral
to the rima pudendi into two massive rolls of fibro-fatty tissue. These rolls
appear to be the homologues of the labia majora1. They are far less affected by oestrin than are the unpigmented tissues which bound the rima pudendi, and
the swelling of which, together with that of the immediate circumanal area,

1 Dr G. B. Wislocki, of Harvard University, informs us that his studies have led him to the
same conclusion.
The Menstrual Cycle of the Primates 45

forms the major part of the swollen sexual skin of the mature chimpanzee. It
follows therefore that, in mature females of this species, the labia majora are
represented by the anterior part of the cushion of pigmented skin which forms
a base for both the unpigmented swollen praeputium clitoridis and the swollen
labia (homologous with the labia minora) which bound the pudendal cleft.

The fact that uterine bleeding was not observed after ovariectomy in the
chimpanzee can be attributed either to the short interval (10 days) between the
operation and the beginning of injections, or to the immature condition of the
ovaries. The second alternative appears to be the more probable. Judging by
the small follicles they contained, it is unlikely that much oestrin was being
secreted at the time of the removal of the ovaries, an inference borne out by
the fact that sexual-skin swelling had not occurred in the three months previous
to the operation. In the circumstances the uterus at that time could not have
been greatly influenced by the hormone, so that it would not have been seriously
affected by the removal of the ovaries.

V. SUMMARY

1. Uterine bleeding did not occur during the ten days following the removal
of the ovaries of an adolescent and ailing chimpanzee.

2. A course of injections of oestrin was begun 10 days after the operation
and continued for 20 days. A total of 21,166 R.U. was administered. Swelling
of the sexual skin began on the third day of injections and persisted until the
animal was killed, on the day of the last injection. At no time did the swelling
exceed the amount characteristic of pubertal chimpanzees, or the amount the
animal had shown during a year of recurring periods of sexual-skin swelling.

3. With the exception of the uterus, the histological changes in the reproductive organs effected by the injections were similar to those reported for
macaques and baboons. Instead of the usual moderate degree of endometrial
hyperplasia, the uterine mucosa shdwed excessive mucosal growth, with
glandular dilatation and cyst formation.

We owe thanks to Dr R. M. Yerkes for his generosity in allowing us to
consult his laboratory protocols, and to Dr Oliver Kamm of the Parke Davis
Company and to Dr Gregory Stragnell of the Schering Corporation for so
liberally providing the supplies of oestrin.

REFERENCES

ALLEN, E. (1927). ‘“‘The menstrual cycle of the monkey, Macacus rhesus: Observations on normal
animals, the effects of removal of the ovaries and the effects of injections of ovarian and
placental extracts into the spayed animals.” Contr. Embryol. Carneg. Instn. 98, vol. xIx,
pp. 1-44.

Harrmay, C. G. (1931). “Relative sterility of the adolescent organism.” Science, vol. LXXIv,
pp. 226-7.

Parkes, A. S. and ZucKERMAN, 8. (1931). ‘The menstrual cycle of the Primates. Part II. Some
effects of oestrin on baboons and macaques.” J. Anat., Lond., vol. Lxv, pp. 272-6.
46 S. Zuckerman and J. F. Fulton

ScHOELLER, W., Dourn, M. and Hountwee, W. (1933). ‘Swelling of external genitalia in castrated female baboons after oral and hypodermic treatment with female follicular sex hormone.” J. Lab. clin. Med. vol. xvi, pp. 926-32.

Spenor, K. W. (1934). “The visual acuity of the chimpanzee.” J. comp. Psychol. (in the Press).

TINKLEPAUGH, O. L. (1932). “Parturition and puerperal sepsis in a chimpanzee.” Anat. Rec. vol.
Li, pp. 193-202.

—— (1933). ‘Sex cycles and other cyclic phenomena in a chimpanzee during adolescence,
maturity, and pregnancy.” J. Morph. vol. tiv, pp. 521-47.

Van WaGENEN, G. (1932). “A study of induced menstruation in the monkey.” Anat. Rec. vol. LII
(Supplement, p. 40) (Abstract).

Van WaGENEN, G. and Zuckerman, S. (1933). “Uterine bleeding of monkeys in relation to
neural and vascular processes. II. Spinal-cord transection and the oestrin level.” Amer. J.
Physiol. vol. cv1, pp. 416-22.

ZucKkERMAN, S. (1930). “The menstrual cycle of the Primates. Part I. General nature and
homology.” Proc. zool. Soc. Lond. pp. 691-754.

ZvucKERMAN, S. and Morssz, A. H. (1934). “The experimental production of excessive endometrial hyperplasia.” Surg. Gynec. Obstet. (in the Press).

ZucKERMAN, S. and Parxgs, A. S. (1932). “The menstrual cycle of the Primates. Part V. The
cycle of the baboon.” Proc. zool. Soc. Lond. pp. 139-91.

EXPLANATION OF PLATE I

Fig. 1. Uterus of experimental chimpanzee after administration of oestrin, showing excessive
hyperplasia.

Fig. 2. Normal uterus of control chimpanzee (about the same dental age) showing resting endometrium.

Fig. 3. Vaginal epithelium of experimental chimpanzee showing cornification and sloughing.

Fig. 4. Swollen sexual skin of experimental chimpanzee showing cornification of surface epithelium
and oedematous condition of underlying tissues.
J ournal of Anatomy, Vol. LDXIX, Part 1 Plate I

 

ZUCKERMAN ann FULTON—TaeE Menstruat Cycie or THE PRIMATES