An abnormal condition of the external genital organs in 16 otherwise normal female guinea-pigs is described. They possessed an hypertrophied penis-like clitoris and horny styles similar to those in the intromittent sac of the normal male penis.

The abnormalities are often asymmetrical, the clitoris and the horny style on one side being more developed than on the other. They may even be absent on one side.

It is suggested that the malformation is a peculiar type of “partial somatic intersexuality,” the external genital organs resembling those in the male guinea-pig.

The condition is identical with that described in the castrated female guineapig experimentally masculinised by testicular transplantation.

There was no indication of the ovaries producing simultaneously female and male sexual hormones :

  • The ovaries were histologically normal.

  • The ovaries when engrafted into castrated males produced the typical female hormonic effect on the mammary glands and had no influence on the penis or on the horny styles.

  • The clitoris and the horny styles of the intersexual females were not affected by removal of the ovaries, whereas in the male removal of the testes caused a pronounced regression of the horny styles even in fully grown animals.

  • The horny styles when cut regenerated even after removal of the ovaries ; there is never a regeneration in the castrated male, but only in the normal male.

The question is discussed whether the described type of intersexuality might be a case of “successive hormonic intersexuality,” both kinds of sexual hormones having been produced simultaneously for a certain time whereas at a later stage only female hormones were secreted. The hypertrophied clitoris and the horny styles would then be considered as “fixed” sex characters persisting after the disappearance of the male sexual hormones. The problem of fixation of sex characters by sexual hormones is considered on experimental lines. The facts observed are rather against the suggestion that the intersexuality described is a case of successive hormonic intersexuality.

Other possibilities of explaining the morphogenetic basis of this peculiar type of intersexuality are also discussed.

The intersexuality described is of an hereditary nature.

The following type of intersexuality was first observed by me in October, 1923. Having since then procured 16 of these intersexual animals, the opportunity was taken of carrying out an experimental investigation of the abnormality. All the observations have been made in conjunction with Mr S. J. Vešnjakov. Dr H. E. V. Voss participated in the observations and operations and carried out the histological part of the work. To these colleagues, and likewise to Mr M. Tiitso and Miss L. Adamberg, who helped in observations and operations, I am much indebted.

More accuracy in the observation of the small organs involved was obtained by frequent photographs, mostly at a magnification of 1·5; all the photographs were taken by Mr Vešnjakov. The direct observations were much facilitated by the use of the new Zeiss “Brillenlupe” which allows a binocular vision atan augmentation of about 1·5 at a distance of about 25 cm.

The completion of this work and the publication of the results were rendered possible by a grant received in August, 1925, from the Ella Sachs Plotz Foundation for the Advancement of Scientific Investigation.

Short preliminary reports were made in 1924 in the C.R. de l’Acad, des Sciences and in 1926 in the Revue Zool. Russe.

In Table I the description of 13 cases is given; 12 of these were discovered among animals bought in Tartu (Dorpat) and in Tallinn (Reval); unfortunately I did not count the total number of animals examined. One intersexual animal was discovered among 63 animals bought in Riga. (For intersexual animals born in the Institute see section 9.)

Table I.
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Table II.
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Table III.
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The intersexuality observed concerns the external genital organs. In a few cases the intersexuality can be detected with greater or less certainty by superficial observation of the genital region, which tends to resemble that of the male, the urethral tubercle being thicker and protruding in such a way as to resemble a penis (Pl. IX, figs. 1-3, Pl. XI, fig. 36; see also Pl. IX, fig. 5). Out of 13 cases this external condition was present only in three. There is an elongation of the prepuce of the clitoris, the prepuce being split on the under-side. Sometimes a red formation protrudes from under the prepuce (Pl. IX, figs. 4 and 5).

When the fold of skin or the prepuce is drawn back, a structure is revealed which in the normal female is never seen by the naked eye. This consists of two red excrescences, i.e. of two corpora cavernosa clitoridis (Pls. IX, X, figs. 57, 1214); sometimes these are separated up to the proximal limit of the prepuce (Pl. IX, figs. 811). Two horny styles are located ventrally to the bodies of the clitoris. The length of the clitoris (measured from the proximal limit of the prepuce) varies greatly. The maximal length observed was 4 mm. The length of the horny styles also shows great variation, the maximal length being about 3-5 mm. In some cases there were only small stumps (just visible to the naked eye) instead of the horny styles. As the horny styles are attached above the proximal limit of the prepuce, the styles, as already mentioned, often protrude below the latter (Pl. IX, figs. 45).

A specially noteworthy feature is that the bodies of the clitoris and the horny styles are often not symmetrical. At first, when we did not examine our cases so carefully as later on, we did not notice any difference between the left and the right side. But later on when measuring the clitoris and the horny styles by means of millimetric paper and by the help of the Zeiss “Brillenlupe” we found that asymmetry is very common ; out of nine cases still alive, four or five reveal lack of symmetry. It is important to note that when the clitoris is symmetrical, then the horny styles are also symmetrical, and vice versa. Cases VI and IX (Pl. X, figs. 1618) are especially illustrative of this. The data for the length in millimetres of the clitoris or of the horny styles are not very exact, but they are sufficiently good to illustrate the differences between the individual cases and the lack of symmetry in some of them.

In every animal, between the body of the clitoris and the prepuce a yellow substance is found, often covering the clitoris with a thick and hard yellow layer. The substance is identical with that which can be found on the penis of the castrated male (Lipschutz, 1916, 1918). Originally it was thought to consist of preputial secretion, but later it was found that both in the castrated male and in the intersexual female the substance can be almost completely dissolved in acetic acid, and consists mostly of precipitated carbonates from the urine.

The above observations make it clear that there is in certain female guinea-pigs a malformation in the genital region consisting of an hypertrophic clitoris and of horny styles ; the latter are similar to those in the intromittent sac of the urethral body of the penis of the male guinea-pig (Cole, 1898) (see Pl. X, fig. 21). Thus a penis-like organ is present in these female guinea-pigs.

As already stated, the condition described was found only in a limited number of cases. Dr Kfizenecky from Brno (Czechoslovakia), to whom I had the opportunity of showing our animals in Tartu, kindly examined about 400 animals in different scientific institutions in Brno and Prag without discovering a single intersexual case.

In four cases (Table I) a post-mortem examination was made and no abnormality was found. The ovaries were of a normal appearance, revealing follicles visible to the naked eye and old corpora lutea. The uterus and the tubes were normal. There was not the slightest indication of testicles or of male tubular organs. Out of 13 animals nine were pregnant or had young in the Institute.

Judging by the external features and by the post-mortem examination, we may conclude that these cases belong to the group of “partial somatic intersexuality”: somatic characters of both sexes being combined in the same individual (see the classification in chap. “Intersexuality,” Lipschutz, 1924, p. 406).

A similar picture was revealed by three other animals, to which we shall refer in section 9.

The spontaneous intersexual deviation here described is identical with thatwhich I discovered ten years ago when working in Steinach’s laboratory in a castrated female guinea-pig with testicular graft (Lipschutz, 1916, 1917, 1918). It is only necessary to compare Pl. IX, figs. 57 and Pl. X, figs. 1517, belonging to cases IV and V in Table I of this paper, with the figures of the masculinised guinea-pig (Lipschutz, 1918, 1924). Both figures are really identical, there being differences in size only. The changes found in the female with testicular graft were considered as caused by specific male hormones having transformed the rudimentary clitoris into a larger penis-like organ and having also produced a growth of the rudiments of horny styles evidently present in every female.

These observations were later fully confirmed by Moore (1921) who found an hypertrophied clitoris with horny styles in two female guinea-pigs with testicular grafts; he relates that the formation was identical with that which I described. Lately Romeis (1923) confirmed our statements, by engrafting a testis into a normal female. Sand (1918) quite independently observed an hypertrophy of the clitoris in five female rats with testicular grafts. Romeis (1923) described a similar experiment on a dog.

There can be scarcely any doubt, therefore, that testicular hormones cause rudimentary organs in the female to develop in a male,direction. An experimental intersexuality, as we see, is determined by testicular transplantation in the female, and likewise by ovarian transplantation in the male.

When, in 1923,1 first saw guinea-pigs with this spontaneous intersexual deviation, I inferred that my conclusions of 1916 based on experimental intersexuality (after testicular implantation) were wrong and that the female guinea-pig, which revealed after testicular transplantation a penis-like organ, must have been in reality a case of spontaneous intersexuality. But it seems evident that this prudence was too far-reaching since the confirmatory statements of Moore (1921) concern two animals out of 18 which received testicular grafts, and only in these two animals did the testicular grafts persist; none of the 16 other animals in which the testicular grafts were absorbed, revealed clitoric hypertrophy.

The conclusion seems justified that the spontaneous intersexuality found in the female guinea-pig is similar to that type of experimental intersexuality which can be determined in normal or castrated female guinea-pigs, rats and dogs by testicular transplantation.

The question now arises whether there is any evidence that the peculiar type of spontaneous intersexuality here described is of a hormonic nature, i.e. is the result of specifically male hormones acting in the female guinea-pig. Is the condition similar to that demonstrated by Morgan in the hen-feathered cock of the Sebright bantam? Morgan (1919,1920) has shown that the hen-feathered Sebright cock assumes after castration the characteristic male plumage, as is the case with the ordinary hen or the Sebright hen after removal of the ovaries. It is evident that the testis, in the Sebright and likewise in some strains of Campines, has the same inhibitory action on the plumage as has the ovary. Pézard, Sand and Caridroit (1924) gave further evidence of this by grafting the testis of a Sebright cock into ordinary cocks which then assumed the plumage of the hen. Can the intersexual condition in our guinea-pigs be changed after castration? Will the ovary of an intersexual guinea-pig engrafted in another animal reveal a male endocrine activity? Our experiments (see sections 4, 5 and 6) show that this is not so. Before entering into a discussion of these experiments on animals with spontaneous intersexuality, it seems necessary to be quite clear about the dependence of the corpora cavernosa penis and of the horny styles in the male guinea-pig upon testicular hormones; the question has been studied with some care in the course of the last few years, and this has made it possible to discuss more fully the details of the general problem of “fixation” of sex characters.

The penis of the guinea-pig is always affected if the testes have been removed. But, as I have shown (Bormann, 1922; Lipschutz, 1924), the condition in the penis in the castrated guinea-pig depends upon the age at which castration is performed. The distal part of the penis which can protrude from the prepuce and which is the characteristic feature of the normal penis of the guinea-pig* is normally about 1 to 112. long; if the testes have been removed, the length of the distal portion is proportional to the age of the animal at the time of castration. There is no further growth of the penis in the animal castrated at an age of about 2 months or more. This is in full accordance with what Marshall (1912), and Arkell and Davenport (1912) found in the case of the horns of sheep, which cease to grow after castration. But contrary to these observations on sheep is the following fact. If castration is carried out on a guinea-pig at an age of several weeks, i.e. before the distal protruding part of the penis has been formed, it is found that the corpora cavernosa penis will nevertheless grow to a certain extent, and the characteristic shape of the normal penis is ultimately attained (see fig. 10 d in Lipschutz, 1924). It is true that the penis always remains much smaller than in the normal guinea-pig or in a guinea-pig castrated at the age of about 2 months. One may suppose that this phenomenon is caused by the testicular hormones having already influenced the corpora cavernosa penis and that this morphogenetic influence is sufficient to promote growth for some time after castration. We can sum up the situation in the following words : what we see on the penis after poit-puberal castration is a character which persists owing to manifest fixation under the influence of testicular hormones (Lipschutz, 1918); what we see after pre-puberal castration (at an age of several weeks) is growth on account of latent fixation under the influence of testicular hormones. That these assumptions are justified is supported by the fact that in male guinea-pigs castrated a few weeks or more especially a few days after birth, the corpora cavernosa penis sometimes overgrow the prepuce to a very limited degree only; the difference between the individual cases depending evidently upon the degree to which the testicular hormones have already influenced the organ after birth.

Of great interest also is the condition of the horny styles in the intromittent sac of the penis in the guinea-pig. They are always reduced after castration (Pl.X, figs. 21 and 22), but the degree of reduction depends upon the age at which castration was performed. The horny styles, which in the fully-grown animal are about 5 to 6 mm. long, in a few weeks or months diminish in length and thickness to form eventually thin stumps of about 1 to 2 mm. The stumps are much smaller or become invisible to the naked eye if castration is performed on younger animals in which the horny styles have a length of only about 1 to 112 mm. Here again we have a sex character depending in its development on testicular hormones and the condition of which, after castration, is to a certain degree determined by the fixing influence of the testis before castration.

The dependence of the horny styles upon testicular hormones can also be easily demonstrated in what I called the regeneration experiment (Lipschutz, 1924, 1925). If the homy style is cut away at a certain distance from its root so that only a stump of about 1 mm. is left (Pl. X, figs. 2327) regeneration occurs in a few weeks. The beginning of the regeneration can be already seen about 3 weeks after cutting and is quite pronounced in another 3 weeks. Though a large number of experiments were performed I never found that a regenerating style attained full normal length ; but full normal length is re-established in cases where the piece removed from a horny style is relatively small (Pl. X, figs. 28, 29). This demonstrates that the increase in length after cutting is really regeneration and not simply a continuation of growth as is the case with the normal horny style; the stump actually grows quicker than a normal style. Contrary to what is seen in the regeneration of the horny style in a normal guinea-pig, there is never any sign of regeneration in the castrated animal, and this is independent of the age at castration.

What will be the condition of the horny styles in the intersexual female after removal of the ovaries? We castrated two intersexual females in which the horny styles were highly developed and measured 3 mm. or more. Animals V and VI (see Table I) after having been observed for 3 and 4 months were subjected to ovariotomy.

After castration, animal V was observed for almost 2 years, and animal VI for about 15 months: both animals are still alive. There was not the slightest change in animal VI (Pl. X, figs. 1517). The horny style on the right side, which had a length of about 3 nun., remained as it was before castration ; it was the same with the clitoris. Quite different was the course of the experiment with animal V (Pl. IX, figs. 711). About 412 months after castration changes of the horny styles were observed with absolute certainty (Pl. IX, fig. 8), and at first sight this was taken as a demonstration of the dependence of the horny styles in the intersexual female upon ovarian hormones. But about a year after castration it was seen (Pl. IX, fig. 9) that the horny style on the left side again increased, attaining almost its original length and its original thickness ; the right horny style remained very small and thin.

Both these experiments show clearly that the condition of the horny styles in the intersexual female is not influenced by castration ; the behaviour of the horny styles is evidently different in the normal male and in the intersexual female.

The changes as observed in animal V after castration seem to reveal fluctuations in the condition of the horny styles, fluctuations which are independent of the ovary. We have already mentioned in section 1 a similar fluctuation (animal VII).

Whereas the clitoris and the horny styles, i.e. the male sex characters of the intersexual female, remained intact after removal of the ovaries, the teats diminished as in the ordinary female after post-puberal castration.

That the clitoris and the horny styles are independent of the ovary can be demonstrated also by the regeneration experiment. Two of these experiments were performed, one on an uncastrated intersexual female (animal IX, see Table I), the second one on an animal castrated more than 13 months previously (animal V, see Table I and section 4). In the uncastrated animal where half of the horny style was removed, the beginning of regeneration was noticed about 7 weeks after cutting and the normal length was soon attained, also the regenerated horny style protruded from under the clitoris as before (Pl. X, figs. 1820). In the castrated animal (Pl. IX, figs. 911) there was no regeneration for about 6 months; afterwards regeneration set in and the left horny style again attained almost its original length. The fact that this regeneration set in only about 5 or 6 months after cutting is of great interest. In this animal (V) the right horny style also was cut, but no regeneration occurred. It seems clear that these contradictory results may be caused by spontaneous fluctuations as mentioned already in sections 1 and 4.

The results of the castration and regeneration experiments show that the intersexual, condition is not caused by ovarian influences. That the ovaries of the intersexual females have normal endocrine capacities is demonstrated by grafting ovaries of intersexual females into castrated males. The ovaries of animals IV and VI (see Table I) were engrafted into the kidney of four males and the results are given in Table IV.

As in the case of the ovaries from ordinary females engrafted into castrated males, a female endocrine effect set in about 3 weeks after the operation; there w’as only one male which did not reveal an endocrine effect. In the three positive cases the maximal development of the teats was attained 6 to 7 weeks after the operation. In one case there was also colostral secretion. On two animals post-mortem examination was made 5 months after transplantation and the mammary glands were found to be highly developed (Pl. XI, figs. 3031). On the other hand, the penis and the seminal vesicles revealed all the signs of castration. The penis was covered in a characteristic manner by the yellow substance mentioned in section 3. The mucosa of the intromittent sac was smooth, the epidermic denticles present in the normal male were lacking. The horny styles which at the time of the operation were 1-2 mm. long (and which in one case were cut), degenerated completely. The seminal vesicles (Pl. XI, figs. 3233) were of the same size and shape as in the ordinary castrated male and their content was fluid or absent; the fluid content did not coagulate with prostatic secretion as does the normal viscous fluid of the vesicles.

It follows from these transplantation experiments that the ovary of the intersexual female exerts, similarly to the normal one, full female endocrine capacities when engrafted into the castrated male, but that it in no way exerts male endocrine capacities.

In case II (Table II) the teats of the feminised male decreased again about 8 months after ovarian transplantation; but even 5 months after the decrease set in they were still much larger (Pl. XI, fig. 34) than in a normal or castrated male (Pl. XI, fig. 35). They resembled closely the teats in the post-puberally castrated female (Pl. XI, fig. 39). This is another good example of a sex character which was fixed under the influence of the sex gland and which persists to a certain degree after the hormonic activity of the sex glands has ceased. In experiments with ovarian grafts we repeatedly made the same observation. We actually possess three other guinea-pigs which were engrafted 10 to 15 months ago with ovaries and which revealed full endocrine activity in such a manner that the teats hypertrophied enormously and the mammary glands secreted. Several months afterwards, degeneration of the teats and the mammary glands set in, but the teats did not attain again the condition seen in the castrated male (Pl.XI,fig. 35) or in the puberally castrated female (Pl. XI, fig. 40); they remained in a condition similar to that of the post-puberally castrated female (Pl. XI, figs. 3739). On the other hand, where the degeneration of the hypertrophied teats in a feminised male sets in soon after the beginning of the hypertrophy, the condition characteristic of the male is in a short time again attained. It seems clear that, after the sex gland ceases to produce hormones, the degeneration of a sex character which was influenced by these hormones is accomplished more completely and sooner the shorter the original hormonic influence lasted. These experiments give full confirmation to the fixation theory as discussed in section 3 with regard to the body of the penis.

Dr Voss examined the histological condition of the ovaries of six cases. I will only mention at this stage that microscopical observation revealed in the ovaries no deviation from the normal. In some cases the adrenals were also examined without any abnormality being found.

Goldschmidt (1920) suggested that there are two different types of intersexuality, (i) hormonic, and (ii) zygotic; the hormonic intersexuality is found in mammals and birds, the zygotic type is found in insects. It might be convenient to distinguish between a hormonic and a peripheral intersexuality, since the hormonic deviation upon which intersexuality in mammals and birds often depends may be also determined by the zygotes. Now, the question arises whether the experiments described above are sufficient to decide to which group the spontaneous intersexuality in the female guinea-pig, as described here, belongs. Is it a hormonic or a peripheral intersexuality? We have seen that the ovary of the intersexual guinea-pig exhibits female endocrine capacities, but not those of the male, and that the hypertrophy of the clitoris and the growth of the horny styles in these intersexual females do not depend upon hormones secreted by the ovary. But this does not exclude the possibility that the intersexuality in this case depends upon male hormones, or upon some other hormones, or that some kind of hormonic deviation is involved. The following suggestions may be taken into consideration:

(a) Are there other sources of male sexual hormones?

Although we are satisfied that the ovary in our intersexual guinea-pigs secretes only female sexual hormones we cannot be sure that somewhere in the body there is not some other source of male sexual hormones. The post-mortem examination gives no support, however, to this suggestion.

(b) Are there other than sexual hormones in play?

Even if it is shown that the intersexuality of the female guinea-pig is really quite independent of both ovarian and testicular hormones, I do not think that such a demonstration would justify the conclusion that the described type of intersexuality is really independent of all hormones. We must take into consideration that the hormonic basis of intersexuality might not be gonadial, but of some other nature. This is only a speculative suggestion, as we have no indication of there being present in out intersexual animals any endocrine abnormalities which could explain the intersexuality observed.

(c) Is it a case of successive harmonic intersexuality?

Of more importance may be the suggestion that the described type of intersexuality belongs hormonically to the group of what one could call “successive intersexuality” (Lipschutz, 1924), heterologous sexual hormones entering into play only temporarily during embryonic or extra-uterine life and a change to a normal hormone production taking place afterwards. That similar conditions are sometimes highly probable is shown by the observations of Pick (1916) on the sow and by Krediet (1921, 1922) on the goat. These observations leave scarcely any doubt that the intersexuality of the sex glands, i.e. the simultaneous presence in the same organism of male and female sex glands, is sometimes only a temporary condition. The antagonism of the sex glands as originally suggested by the ingenious work of Steinach (1916) and as later verified experimentally by the writer and his associates (1924–1926) may explain the disappearance of one of the two glands. It has been shown experimentally (Lipschutz and Voss) that follicular development of the ovary is more or less inhibited by a testis if simultaneously present. One might suggest, therefore, that in some cases a somatic intersexuality which was at first of hormonic nature afterwards became peripheral, and that this is true for our cases of intersexuality in female guinea-pigs. One might suppose that these guinea-pigs originally were also intersexual in respect to their sex gland, but that the male endocrine tissue eventually disappeared under the antagonistic influence of the ovary and so these guinea-pigs became hormonically monosexual.

Can such an assumption be brought into line with the descriptive and experimental data recorded above from the penis and clitoris and from the horny styles ?

We have seen in section 3 that the condition of a sex character depends upon the length of time it has been exposed to the influence of sexual hormones. The sexual hormones are capable of fixing a sex character and of determining its further fate even when the hormones themselves are no longer present. That this suggestion cannot be adopted for all the sex characters in mammals and birds is shown by many observations and especially by those of Marshall on the horns of sheep, of Pézard on the head apparel of fowls, and of Lipschutz on the penis of the rabbit. But for the corpora cavernosa of the penis in the guinea-pig the fixation theory seems to hold (see section 3). Now, if the assumption is correct that the intersexuality of these females is of a successive hormonic type, then the hypertrophied clitoris and the horny styles which are no longer subject to the influence of male sexual hormones must be of a fixed type similar to that in the castrated male. This may be the case with the corpora cavernosa which, as shown experimentally, really persist in the male guinea-pig after castration. But great difficulties arise with the horny styles. These are also fixed to a certain degree, as the stumps in the post-puberally castrated male are much more developed than after pre-puberal castration. In the intersexual female, however, they are often longer and thicker than in the post-puberally castrated male. Further, the horny styles of the intersexual female regenerate after cutting, contrary to what is the case in the castrated male. This is incompatible with the assumption that the horny styles of the intersexual female are fixed characters which persist after the male hormones have ceased to be produced and ceased to influence the body.

(d) Is it a case of somatic intersexuality determined by monosexual hormones entering into play after the critical time?

Herbst (1901) has been the first to emphasise the great importance to be attributed to the time factor in explaining the different types of somatic intersexuality. According to his theory, furtherance or inhibition of the anlage of different sex characters by the sexual hormones must take place at a given time ; if this is not the case, and the sexual hormones do not enter into play at the critical time, an intersexual malformation will be the result. Since then several authors [Goldschmidt (1917, 1920) in insects, Lillie (1917, 1923), Lipschutz (1919, 1924), Crew (1923), Baker (1925) in mammals] have discussed the importance played by the time factor in the morphogenesis of the different types of intersexuality.

Whereas in the preceding paragraph the evidence of a fixation of sex characters by the influence of hormones was discussed, it may be mentioned that Herbst’s theory itself suggests that the plasticity of the tissue or its capacity to react in a certain morphological way to sexual hormones changes with the time even when it is not previously influenced by hormones.

In a similar way Crew (1923) attempted to explain certain cases of intersexuality in pigs. These were sex-intergrades with internal tubular characters of both sexes and external genital organs transitional between female and male ; only testicular tissue was present. Crew suggested that these pigs are genetically males, the somatic abnormality being caused by the male sexual hormones beginning their stimulating or inhibiting influence too late or that they were produced in too small quantities at the critical time. Theoretically there is no objection to such a suggestion. Baker has, it is true, pointed out that some features in intersexual pigs render difficult the acceptance of the theory, but would it be possible to explain the sex-intergrades in female guinea-pigs by Crew’s theory? There are several points which render this rather difficult. We might assume that our intersexual guinea-pigs are genetically females in which the female sex hormones entered into play too late, and suppose that those organs of the opposite sex which differentiate early are more pronounced than those which differentiate later. But in reality we see in our intersexual guinea-pigs just the opposite: there are no male tubular organs and there are well-developed corpora cavernosa and horny styles which differentiate during extra-uterine life.

As far as I know there is only one other case of intersexuality in the guinea-pig which has been hitherto observed. Loeb (1918) described a guinea-pig without male or female internal tubular organs and without a vagina or a penis. Testicular tissue was found in the abdomen. There were interstitial cells and infantile seminal tubules. The mammary glands were more developed than in an ordinary male. Loeb assumed that the somatic intersexuality in this case was caused by some abnormality of a somatic or peripheral nature. As I have pointed out else where (1924 a), Loeb’s observation might possibly be regarded as a case of successive hormonic intersexuality. But the peculiar type of intersexuality in the female guinea-pig described in this paper seems incapable for the moment of receiving a satisfactory explanation on a purely hormonic basis. It is the same with the intersexual opossum described by Hartman (1925). We are indeed very far from an understanding of all these cases notwithstanding the great achievements in the last few years.

(e) Riddle’s ‘‘developmental” or “physiological” theory of atypical sex characters in birds

In birds the evidence seems to be very conflicting from the point of view of the hormonic theory; this was recently emphasised by Riddle (1925). This author has tried to introduce a new experimental principle into the discussion of cases which are atypical in respect to somatic or gonadial sex characters. Riddle (1920, 1923) showed that by temporarily subjecting dove embryos to altered oxygen pressure and to low temperatures, unusually high percentages of individuals with atypical gonads can be obtained. He therefore holds the view that an aberration in the development of the gonads or of other organs might be induced by temporary functional disturbances at earlier and “critical stages” (Stockard), without there being any genetic or chromosome deviation. It is clear that this point of view is quite different from that on which we have based our discussion of the spontaneous intersexuality in the guinea-pig. It is doubtful whether Riddle’s theory helps to elucidate the case of intersexual guinea-pigs. For the moment no experiments justify its application to mammals.

We were unable to find any exact evidence of the genetical origin of our intersexual guinea-pigs. In one case an intersexual female was born from an intersexual female mated with her son ; in a second case we obtained an intersexual female from a normal female mated with the same male as above. In a third case an intersexual female was born from an intersexual female which was already pregnant when purchased. The above-mentioned male was mated with nine normal females ana 11 normal females were born. Two normal females were born from intersexual females mated with normal males. The data concerning the three intersexual guinea-pigs of known origin and the two normal guinea-pigs born from intersexual females are given in Table V.

Table IV.
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Table V.
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The animals were observed sufficiently long to determine definitely whether there was or was not an hypertrophy of the clitoris.

Arkell
,
T. R.
and
Davenport
,
C. B.
(
1912
).
Science
,
35
. (Quoted from Marshall, Physiology of Reproduction, London, 1922.)
Baker
,
J. R.
(
1925
).
Brit. Journ. Exp. Biol
.
2
,
247
.
Bormann
,
F.
(
1922
).
Skand. Arch.f. Physiol
.
42
,
240
.
Cole
,
F.
(
1898
).
Journ. Anat. and Physiol
.
32
,
141
.
Crew
,
F. A. E.
(
1923
).
Proc. Roy. Soc. B
,
95
,
90
.
Crew
,
F. A. E.
(
1924
).
Journ. Obstetr. and Gynaec. of the Brit. Emp
.
31
, No.
3
.
Goldschmidt
,
R.
(
1917
).
Endocrinology
,
1
,
433
.
Goldschmidt
,
R.
(
1920
).
Mechanismus u. Physiologie der Geschlechtsbestimmung
.
Berlin
.
Hartman
,
C. G.
(
1925
).
Anat. Rec
.
29
,
283
.
Herbst
,
C.
(
1901
).
Formative Reize in der tierischen Ontogenese
. Leipzig.
Krediet
,
G.
(
1921
).
Biolog. Zentralbl
.
41
,
447
.
Krediet
,
G.
(
1922
).
Anatom. Anz
.
55
,
502
.
Lillie
,
F. R.
(
1917
).
Journ. Exp. Zool
.
23
,
371
.
Lillie
,
F. R.
(
1923
).
Biol. Bull
.
44
,
47
.
Lipschutz
,
A.
(
1916
).
Anz. d. Akad. d. Wissensch. Wien
, No.
27
.
Lipschutz
,
A.
(
1917
).
Journ. Physiol
.
51
,
283
.
Lipschutz
,
A.
(
1918a
).
Arch.f. Entwicklungsmech
.
44
,
196
.
Lipschutz
,
A.
(
1918b
).
Arch. f. Entwicklungsmech
.
44
,
207
.
Lipschutz
,
A.
(
1919
).
Die Pubertätsdrüse u, ihre Wirkungen
.
Bern
.
Lipschutz
,
A.
(
1924a
).
The Internal Secretions of the Sex Glands
.
Cambridge, Baltimore
.
Lipschutz
,
A.
(
1924b
).
C.R. Soc. Biol
.
90
,
274
.
Lipschutz
,
A.
(
1924c
).
C.R. de l’Acad. d. Sci
.
179
,
1625
.
Lipschutz
,
A.
(
1925
).
Pflüger’s Arch
.
207
,
548
.
Lipschutz
,
A.
and others
(
1926
).
Pfiüger’s Arch
.
211
,
697
(see p. 714).
Lipschutz
,
A.
,
Krause
,
W.
,
Voss
,
H. E. V.
,
Tiitso
,
M.
,
Perli
,
H.
and
others
(
1924-1926
).
C.R.Soc. Biol. 89-93; Pfiüger’s Arch
.
207
, 208, 211.
Loeb
,
L.
(
1918
).
Biol. Bull
.
34
,
33
.
Marshall
,
F. H. A.
(
1912
).
Proc. Roy. Soc. B
,
85
. (Quoted from Marshall, Physiology of Reproduction, London, 1922.)
Moore
,
C. R.
(
1921
).
Journ. Exp. Zool
.
33
,
365
.
Morgan
,
T. H.
(
1919
).
Carn. Instit. of Washington, Publ
.
285
.
Morgan
,
T. H.
(
1920
).
Biol. Bull
.
39
,
231
.
Pézard
,
A.
,
Sand
,
K.
and
Caridroit
,
E.
(
1924
).
C.R. Soc. Biol
.
90
,
676
.
Pick
,
L.
(
1916
).
Berl. Klin. Wochenschr
.
53
,
1142
.
Riddle
,
O.
(
1920
).
Proc. Soc. Exp. Biol, and Med
.
17
,
88
.
Riddle
,
O.
(
1923
).
Amer. Journ. Anat
.
32
. (Quoted from Riddle (1925).)
Riddle
,
O.
(
1925
).
Brit. Journ. Exp. Biol
.
2
,
211
.
Romeis
,
R.
(
1923
).
Anat. Anz
.
57
,
263
.
Sand
,
K.
(
1918
).
Experimentelle Studier over Kenskarakterer hos Pattedyr
.
Copenhagen
.
Sand
,
K.
(
1918
).
Pfiüger’s Arch
.
173
.
Steinach
,
E.
(
1916
).
Arch.f. Entwicklungsmech
.
42
,
307
.

Plate IX

Fig. 1. External genital region of abnormal female guinea-pig (Table I, case I). × 34. Penis-like organ protruding from under prepuce; the top of the left style also visible.

Fig. 2. External genital region of normal female guinea-pig. ×34.

Fig. 3. External genital region of normal male guinea-pig. Penis riot protruding, ×34.

Fig. 4. Abnormal female (Table I, case III). Both horny styles protruding. Uterus pregnant; teats enlarged.

Fig. 5. Abnormal female (Table I, case V). External genital region; side-view. Horny styles protruding.×112.

Fig. 6. Abnormal female (Table I, case V). Prepuce drawn back. Enlarged clitoris and horny styles visible.×112.

Fig. 7. Abnormal female (Table I, case V). Front view. Horny styles not quite symmetrical. The vagina is seen below. ×112.

Figs. 8-11. Abnormal female (Table I, case V). Castrated. Regeneration of the horny styles (Tabels II and III), ×112.

Fig. 8. Seven months after castration. Horny styles reduced.

Fig. 9. Thirteen months after castration. Left horny style completely regenerated.

Fig. 10. Thirteen months after castration. Horny styles cut away (same day as Fig. 9).

Fig. 11. Six and a half months after cutting the horny styles ; twenty months after castration.Left horny style regenerated.

Fig. 12. Abnormal female (Table I, case IV). Ovary of this animal produced féminisation of castrated male (see Table IV).

Fig. 12. External genital region. Prepuce drawn back. Enlarged symmetrical clitoris and horny styles. Vagina below.×112.

Fig. 1. External genital region of abnormal female guinea-pig (Table I, case I). × 34. Penis-like organ protruding from under prepuce; the top of the left style also visible.

Fig. 2. External genital region of normal female guinea-pig. ×34.

Fig. 3. External genital region of normal male guinea-pig. Penis riot protruding, ×34.

Fig. 4. Abnormal female (Table I, case III). Both horny styles protruding. Uterus pregnant; teats enlarged.

Fig. 5. Abnormal female (Table I, case V). External genital region; side-view. Horny styles protruding.×112.

Fig. 6. Abnormal female (Table I, case V). Prepuce drawn back. Enlarged clitoris and horny styles visible.×112.

Fig. 7. Abnormal female (Table I, case V). Front view. Horny styles not quite symmetrical. The vagina is seen below. ×112.

Figs. 8-11. Abnormal female (Table I, case V). Castrated. Regeneration of the horny styles (Tabels II and III), ×112.

Fig. 8. Seven months after castration. Horny styles reduced.

Fig. 9. Thirteen months after castration. Left horny style completely regenerated.

Fig. 10. Thirteen months after castration. Horny styles cut away (same day as Fig. 9).

Fig. 11. Six and a half months after cutting the horny styles ; twenty months after castration.Left horny style regenerated.

Fig. 12. Abnormal female (Table I, case IV). Ovary of this animal produced féminisation of castrated male (see Table IV).

Fig. 12. External genital region. Prepuce drawn back. Enlarged symmetrical clitoris and horny styles. Vagina below.×112.

Plate X

Figs. 13 and 14. Same abnormal female as Fig. 12, Plate IX.

Fig. 13. Front view. ×325.

Fig. 14. Side view. ×112.

Figs. 15, 16, 17. Abnormal female (Table I, case VI). Castrated; see Tables 2 and 4. ×112.

Fig. 15. Before castration. Clitoris and horny styles not symmetrical.

Fig. 16. Five months after castration. No change.

Fig. 17. One year less 20 days after castration. No change.

Figs. 18, 19, 20. Abnormal female (Table I, case IX; Table III). Regeneration of cut horny style; see Table III. ×112.

Fig. 18. Before operation. Horny styles asymmetrical.

Fig. 19. Immediately after cutting the horny style.

Fig. 20. Six and a half months after cutting. Regeneration.

Fig. 21. Horny styles of fully-grown male guinea-pig (Prot. No. 497; 690 g.). ×112.

Fig. 22. Same animal as Fig. 21 ; six months after castration. ×112. Horny styles reduced in length and thickness. Mucosa of the intromittent sac smooth (disappearance of denticles).

Figs. 23-27. Partial regeneration of horny style in fully-grown normal guinea-pig (Prot. No. 469; 790 g.). ×112.

Fig. 23. Before cutting.

Fig. 24. Just after cutting.

Fig. 25. Eighteen days after cutting.

Fig. 26. Fifty-one days after cutting.

Fig. 27. Eight months after cutting.

Figs. 28-29. Complete regeneration of horny style in fully-grown normal guinea-pig (Prot. No. 553). ×112.

Fig. 28. Just after cutting about half of the right horny style.

Fig. 29. Five months after cutting.

Figs. 13 and 14. Same abnormal female as Fig. 12, Plate IX.

Fig. 13. Front view. ×325.

Fig. 14. Side view. ×112.

Figs. 15, 16, 17. Abnormal female (Table I, case VI). Castrated; see Tables 2 and 4. ×112.

Fig. 15. Before castration. Clitoris and horny styles not symmetrical.

Fig. 16. Five months after castration. No change.

Fig. 17. One year less 20 days after castration. No change.

Figs. 18, 19, 20. Abnormal female (Table I, case IX; Table III). Regeneration of cut horny style; see Table III. ×112.

Fig. 18. Before operation. Horny styles asymmetrical.

Fig. 19. Immediately after cutting the horny style.

Fig. 20. Six and a half months after cutting. Regeneration.

Fig. 21. Horny styles of fully-grown male guinea-pig (Prot. No. 497; 690 g.). ×112.

Fig. 22. Same animal as Fig. 21 ; six months after castration. ×112. Horny styles reduced in length and thickness. Mucosa of the intromittent sac smooth (disappearance of denticles).

Figs. 23-27. Partial regeneration of horny style in fully-grown normal guinea-pig (Prot. No. 469; 790 g.). ×112.

Fig. 23. Before cutting.

Fig. 24. Just after cutting.

Fig. 25. Eighteen days after cutting.

Fig. 26. Fifty-one days after cutting.

Fig. 27. Eight months after cutting.

Figs. 28-29. Complete regeneration of horny style in fully-grown normal guinea-pig (Prot. No. 553). ×112.

Fig. 28. Just after cutting about half of the right horny style.

Fig. 29. Five months after cutting.

Plate XI

Fig. 30. Enormous hypertrophy of teats in castrated male guinea-pig about five months after transplantation of ovary from abnormal female (cp. Figs. 12-14, Table IV, case I). Nat. size.

Fig. 31. Same animal as Fig. 30. Highly developed mammary glands visible. Nat. size.

Fig. 32. Same animal as Figs. 30 and 31. Seminal vesicles highly reduced as in castrated male (cp. Fig. 33). Nat. size. On the right, kidney with ovarian graft in the medulla.

Fig. 33. Seminal vesicles of normal guinea-pig (Prot. No. 370; 550 g.). Nat. size. Animal with testicular fragment, sixteen months after operation ; vesicles not seen in whole length as the ends were found grown together with surrounding tissue and had to be cut.

Fig. 34. Castrated male guinea-pig in which the mammary glands underwent maximal development secretory activity under the influence of ovarian transplantation (see Table IV, case II) and then again decreased, without attaining normal male condition. Fourteen months after ovarian transplantation, about seven months after beginning of regression. Nat. size.

Fig. 35. Male guinea-pig, 50 days after castration (Prot. No. 586; 400 g.; unsuccessful ovarian transplantation). Nat. size.

Fig. 36. Normal female guinea-pig which had already given birth to young; not actually pregnant (Prot. No. 849; 660 g.). Nat. size.

Fig. 37. Castrated male guinea-pig, 50 days after successful ovarian transplantation. Mammary secretion (Prot. No. 584; 400 g.). Nat. size.

Fig. 38. Same animal as Fig. 37. Several months after beginning of regression (650 g.). Nat. size.

Fig. 39. Female guinea-pig, ten months after post-puberal castration (Prot. No. 573; weight at castration 590 g.; last partus three months before castration; weight when photographed 710 g.). Nat. size.

Fig. 40. Female guinea-pig, fourteen and a half months after castration (Prot. No. 539 ; weight at castration 275 g. ; weight when photographed 650 g.). Nat. size.

Fig. 30. Enormous hypertrophy of teats in castrated male guinea-pig about five months after transplantation of ovary from abnormal female (cp. Figs. 12-14, Table IV, case I). Nat. size.

Fig. 31. Same animal as Fig. 30. Highly developed mammary glands visible. Nat. size.

Fig. 32. Same animal as Figs. 30 and 31. Seminal vesicles highly reduced as in castrated male (cp. Fig. 33). Nat. size. On the right, kidney with ovarian graft in the medulla.

Fig. 33. Seminal vesicles of normal guinea-pig (Prot. No. 370; 550 g.). Nat. size. Animal with testicular fragment, sixteen months after operation ; vesicles not seen in whole length as the ends were found grown together with surrounding tissue and had to be cut.

Fig. 34. Castrated male guinea-pig in which the mammary glands underwent maximal development secretory activity under the influence of ovarian transplantation (see Table IV, case II) and then again decreased, without attaining normal male condition. Fourteen months after ovarian transplantation, about seven months after beginning of regression. Nat. size.

Fig. 35. Male guinea-pig, 50 days after castration (Prot. No. 586; 400 g.; unsuccessful ovarian transplantation). Nat. size.

Fig. 36. Normal female guinea-pig which had already given birth to young; not actually pregnant (Prot. No. 849; 660 g.). Nat. size.

Fig. 37. Castrated male guinea-pig, 50 days after successful ovarian transplantation. Mammary secretion (Prot. No. 584; 400 g.). Nat. size.

Fig. 38. Same animal as Fig. 37. Several months after beginning of regression (650 g.). Nat. size.

Fig. 39. Female guinea-pig, ten months after post-puberal castration (Prot. No. 573; weight at castration 590 g.; last partus three months before castration; weight when photographed 710 g.). Nat. size.

Fig. 40. Female guinea-pig, fourteen and a half months after castration (Prot. No. 539 ; weight at castration 275 g. ; weight when photographed 650 g.). Nat. size.

*

In the guinea-pig and in the rabbit it is not homologous to the glans in man.