On Sex-Intergrade Pigs: Their Anatomy, Genetics, and Developmental Physiology

This paper deals with sexually abnormal pigs, called by farmers “wildews” or “wilgils.” In the first part of the paper the anatomy of nine of these pigs is described ; in the second part facts are recorded proving the inheritance of a tendency to the condition ; the third deals with the physiology of their development ; and in the fourth allusion is made to their sexual instincts.

Index to Lettering of Figures.

The nine sex-intergrade pigs described below are arranged in a series beginning with the most female and ending with the most male. Figures of the reproductive organs of normal male and female pigs may be found in Sisson.⁹ 

No. 1.—Age, 6 to 7 months. Father, Large White; mother, Large Black. This specimen differs from a normal female in the following points:—

(1) On the right side, in the place of an ovary, is a testis with a patch of ovarian tissue on the, surface at the anterior end. There is a sharp line of demarcation between ovarian and testicular tissue. There is also a raised area which is to be seen in section (Plate 1. Fig. 1) to consist of testis tissue lying outside the tunica albuginea, almost giving the impression that a new set of sex cords was proliferated after the formation of the albuginea, and that these cords (the homologues of the cords of Pflüger) were converted into seminiferous tubules instead of giving rise to ovarian follicles. The seminiferous tubules are degenerate and mostly without lumina; there is a single layer of nuclei near the tunica propria. (This specimen is a true hermaphrodite, for there is a normal ovary on the left side.) Associated with the testis is an epididymis (cystic at EC in the figure) and a pampiniform plexus. (2) A vas deferens runs in the broad ligament on the right side. (3) The right Fallopian tube is minute, and runs over the surface of the epididymis. (4) Bulbo-glandularis muscles are slightly developed. (5) The clitoris is enlarged, and projects through the vulva to the exterior. The retractor clitoridis muscles are also enlarged. (6) There is a very small conical projection on the belly, just behind the navel.

No. 2 is another true hermaphrodite, with an ovary on the left side and an ovo-testis on the right side. The ovarian patch (Plate I. Fig. 2) is sharply marked off from the testicular tissue, and is in just the same place as in No. 1. This specimen differs from No. 1 only in the following points: (1) There is less interstitial tissue in the testis. (2) The epididymis is slightly differently applied to the testis, and is not cystic. (3) The vagina is rather thin-walled. (4) The urethra is somewhat constricted posteriorly. (5) The clitoris is not visible externally. (6) The ventral labial commissure protrudes greatly.

The small size of the Fallopian tube on the right side, and its position on the epididymis, are shown in Plate I. Fig. 4. Plate I. Fig. 3 is the Fallopian tube of a young normal female: Plate I. Fig. 4 is the right Fallopian tube and adjacent part of the epididymis in this specimen. This specimen was sired by the same boar as No.1.

No. 3, — Age, 7 months. Father, pedigree Large White; mother, cross-bred Large White.

The chief points in the anatomy of No. 3 are as follows:—

(1) The gonads are testes on both sides. They were just visible externally in the living animal, but were not in a proper scrotum. The seminiferous tubules are similar to those of No. 1. Interstitial tissue is normal in amount. On the surface of the left testis are raised patches of testicular tissue lying outside the albuginea, similar to the patch described and figured in the case of No. 1. (2) There is an epididymis and a pampiniform plexus on each side, the left epididymis being improperly attached to the testis and the right being cystic in one place. (3) The vasa deferentia are well developed on each side. (4) There are elongated narrow vesiculæ seminales closely bound to the cervix uteri and vagina. They are normal histologically, though the tubules are a trifle small. (5) There is a small prostate gland, normal histologically. (6) Histologically normal bulbo-urethral glands are present. (7) The Fallopian tubes are similar to the right Fallopian tubes of Nos. 1 and 2. (8) The uterine cornua are normal. (Plate II. Figs. 5 and 6, which are sections through the cornua of a young normal female and of this specimen respectively.) (9) The corpus and cervix uteri are ill-developed. The cervix is almost entirely lacking in the large internal prominences so characteristic of the normal female. (10) The vagina is rather thin-walled, and opens by a very small opening into the urethra. (11) The urethra is like the pelvic part of the urethra of a male. The ductus ejaculatoria open on each side of the colliculus :seminalis. (12) The clitoris is much enlarged and has two hard nail-like structures at its tip. The retractor muscles are very large and the corpus cavernosum clitoridis is of great diameter and pursues a zigzag course. (13) The aperture of the vulva is small and crescentic, the horns of the crescent pointing ventrally. The ventral labial commissure is enlarged and turned upwards to reach as high as the anus. (14) There is the usual conical post-umbilical projection on the belly, which appears to exist in all sex-intergrade pigs.

No. 4—Age, 10 months. Pedigree Middle White.

The anatomy of No. 4 is sufficiently well shown in the figure, and requires little description. The corpus and cervix uteri are swollen and thin-walled, and the cornua are swollen and less deeply ridged internally than in a normal female. vesiculæ seminales are absent. The testes are abdominal. The tubules are further apart than in any of the other specimens. They are entirely degenerate.

No. 5 — The testes lie just beneath the skin. The uterus and vagina are thin-walled and enormously swollen. The prostate, which is not visible externally, is normal histologically. The vesiculæ seminales have small tubules separated by excess of intcrtubular tissue.

No. 6. — Age 7 months. Pedigree Large White.

This pig had external testes, and was castrated when young. It is remarkable for the rudimentary condition of the internal reproductive organs.

The uterine cornua were apparently removed at castration. The corpus and cervix uteri, the vagina, and the urethra are all extremely small. There are no signs of vasa deferentia, nor of vesiculæ seminales, nor of prostate gland, nor of bulbo-urethral glands. The fact that the uterus is very poorly developed in this specimen, as well as in the only other specimen that was castrated when young (No. 7), is referred to in the part of this paper which deals with the physiology of development of sex intergrades.

The clitoris protrudes between the labia, and the ventral commissure projects upwards.

No. 7. — Age about 8 months. Father, Large White; mother, Large Black.

This pig also had external testes, and was castrated at the age of about six weeks. As is to be expected in a castrated pig, the vasa deferentia, vesiculæ seminales, and bulbo-urethrals are small and poorly developed. The tubules of the vesiculæ seminales are very small and separated by a large excess of intertubular tissue. The bulbo-urethrals are fairly normal histo logically, but the amount of connective tissue is greater than normal. The prostate, rather surprisingly, is fairly well developed. The acini are somewhat larger than normal, but are separated by excess of connective tissue.

The remains of the cornua uteri are very narrow, especially on the right side. The corpus, cervix, and vagina are minute. The pelvic part of the urethra is of the male type, with well-developed colliculus. The corpus cavernosum and the retractor muscles of the erectile organ are larger than those of any of the other specimens. The external organs are most remark able. There is a ridge of tissue in the place of the vulva, and below it is a large cylindrical upwardly turned structure, near the end of which on its upper surface the urethra opens by a small crescentic slit. This structure probably represents a much enlarged clitoris which has fused with the ventral labial commissure and has carried the latter with it in its enlargement. This pig was sired by the same boar as Nos. 1 and 2.

No. 8. — This pig I obtained in the New Hebrides. No figure is given of it, because it resembles No. 9 so closely. The chief differences from No. 9 are the following: (1) The right testis is abnormal, consisting largely of fibrous tissue. (2) The left testis differs from those of all my other specimens in that spermatocytes are present. Many tubules show nuclei in synizesis and in the pachytene stage. (3) The external genitalia are those of a normal female except that the clitoris is slightly enlarged. (4) This specimen had well developed tusks.

No. 9. — Age 10 weeks. Pedigree Large White.

The anatomy is well shown in the figure. No sign of the derivatives of the Müllerian ducts persists. The testes were in a scrotum precisely similar to that of a normal boar. It is therefore remarkable that the seminiferous tubules are very far apart, completely lacking in spermatocytes and undergoing fatty degeneration. There is a great hyperplasia of interstitial cells. The conical prominence on the belly is better differentiated in this specimen than in the others. It is slightly hollowed out anteriorly.

In man a form of hypospadia is known to be sex-linked in its inheritance, and several cases of more than one “pseudo-hermaphrodite” being born of the same parents are recorded by Neugebauer.⁷ 

It was by the natives of the New Hebrides that my attention was first drawn to the subject of the inheritance of a tendency to sexual abnormality in pigs. Sex-intergrade pigs are surprisingly common on some of the islands ; one finds them in nearly every little village. The natives make use of them in certain of their religious rites, and hence it is to their advantage to be able to breed them. On one island the method adopted is to mate a sow known to have produced sex-intergrades with a boar from an intergrade-producing family. On other islands the sows alone are regarded as being responsible for the production of intergrades, and in the case of two islands, on which there were no indigenous intergrades, intergrade-producing sows were imported to produce them.

The fact that the New Hebrideans are right in supposing that a tendency to sexual abnormality in pigs is inherited is well shown by information which I have collected from farmers since my return to Great Britain. I quote here some typical cases.

The above is the pedigree of a family of pure-bred Large White pigs. The boar which sired the intergrades has given only normal offspring with the other sows with which it has been mated. The sow labelled “c” is distantly related to the sows labelled “a” and “b.” The intergrade labelled “d” is No. 6 of this paper.

Another case, in which unfortunately no accurate breeding records were kept, is the most striking. A farmer bought a bear which sired ten or twelve intergrades with various unrelated sows. Three of these are Nos. 1, 2, and 7. As many as three intergrades were born in a single farrow. None of his sows produced intergrades before this boar was bought, nor have any intergrades been produced since another boar has been used in its stead.

Another case concerns a pedigree Large White sow which had been producing normal offspring for some time until its owner bought a new pedigree Large White boar and mated her with him. She produced sex-intergrades from that time forward, being mated each time with the same boar. One intergrade appeared in one farrow, three in another, four in another. The same boar sired no intergrades with any other sow except one, with which it was only mated once.

There are other cases of a boar siring intergrades with more than one sow.

Table I. shows the numbers of normal males, sex-intergrades, and normal females born of various intergrade producing parents. From the table it is seen that the ratio of normal pigs to intergrades is 8 : 1. Granting that intergrades are either all modified males or all modified females, and supposing that the abnormality is caused by a double dose of a recessive factor affecting one sex only, then the ratio produced on mating two heterozygous individuals together would be seven normals to one intergrade, an approximation to the ratio shown in the table. The pure recessive of the non-affected sex would be an intergrade-producer giving twice as many intergrades as the heterozygous intergrade-producers.

But I think that the proportion of intergrades given by the table is probably too high, for the following reason. In some of the cases, which I have been unable fully to investigate owing to lack of properly kept breeding-records, the same parents may have produced one or more farrows containing no intergrades before producing the farrow or farrows tabulated, thus giving prominence only to the farrows produced after the first intergrade was born and making the proportion of intergrades too great.

Of course more than one factor may be concerned, and it is not impossible that differences in potency of the sex-factor (or factors) are at work, as in Goldschmidt’s intersexes in Lymantria.⁴  Further speculation about the factor or factors concerned would be useless until more facts are known. Nevertheless it seems just worth while to mention that the fact that intergrade-producing females are commoner than intergrade-producing males, could be accounted for on the assumption that two recessive factors are concerned, one sex-linked and one autosomal, if sex-intergrades be regarded as modified males. (See below, however, on the probable genetic sex of sex-intergrades.)

There are several reasons for supposing that sex-intergrades in pigs are not free-martins. Firstly, the testes and epididymes are almost always well developed (though the seminiferous tubules are degenerate), whereas in free-martins it is unusual for the embryonic ovary to be so completely changed as to have lost all trace of its true nature; secondly, fusion of chorions has not been described in pigs ; thirdly, sex-intergrades have been born singly or co-twin with normal females ; and lastly, I find that a tendency to the condition is transmitted by the male parent.

The only serious attempt that has been made to give an explanation of sex-intergrades of this sort is that of Crew²  who dissected a large number of cases in goats and pigs. Crew’s hypothesis, stated briefly, is that the growth of the primordia of the various sexual organs requires either to be stimulated or to be inhibited at various definite times in the course of growth. If for any reason an organ is not stimulated soon enough, it will fail to develop completely however great the stimulus may be later on: and on the other hand, if the growth of an organ is not inhibited sufficiently early, it will continue to develop, at least to some extent, though the suppressing influence may be very great in later stages. He supposes that intergrades are really males, in which the hormone which stimulates male primordia to develop and which inhibits the growth of female primordia was for some reason or other produced too late, or was produced in too small quantities at the critical times.

An objection to this view is that the perfect development e.g. of the uterine cornua in certain cases is unexplained. Plate II. Figs. 5 and 6, showing transverse sections through the cornua of a young normal sow and of sex-intergrade No. 3 respectively, illustrates the histological perfection of the latter. It is well known that in an ovariotomised rat the uterus degenerates (Livingston⁶ ) and yet Crew’s hypothesis demands that the uterine cornua may not only persist but may even develop to the normal extent in the absence of ovarian tissue.

It seems more probable that the embryo of every sex-intergrade was a hermaphroditus verus containing both testicular and ovarian tissue, and that the differentiation of the various organs took place under the antagonistic influence of the two hormones. On this hypothesis the degree of inter-sexuality attained depends upon the relative and absolute quantities of each hormone present at various times during development. Usually the ovarian tissue disappears completely, or at any rate is not visible externally; but in some cases quite a large patch of ovarian tissue remains, and in others a whole gonad is ovarian.

Its disappearance in the majority of cases is what we should expect. Of course it is well known (Sand ⁸ ) that intratesticular ovarian transplants often persist quite well. But persisting is a very different matter from growing and differentiating. All the evidence at our disposal, namely that derived from work on the free-martin,^6,11  leads us to suppose that the influence of the male hormone is to transform embryonic ovarian tissue into testicular.

On this theory the uterine cornua grow and differentiate for some time at any rate under the influence of the ovarian hormone, so that it is not surprising that they sometimes attain a high degree of differentiation. This they would do when the amount of ovarian tissue was great and the amount of testicular tissue was small at the critical times. The fact that they persist in the apparent absence of ovarian tissue, points to the idea that Ungulates differ from Rodents in that the ovary is not necessary for their persistence (though it is necessary for their differentiation). I am studying this point experimentally. If it is found that the uterus of ovariotomised pigs does degenerate, then it is probable that there is a certain amount of ovarian tissue or a certain number of the cells which produce the ovarian hormone somewhere within the testis of these sex-intergrades-though only laborious sectionig of the whole gonad could disclose it. The fact that those sex-intergrades which were castrated when young (namely Nos. 6 and 7) have very small and poorly differentiated uteri, is in favour of the latter hypothesis.

On Crew’s hypothesis one would expect the external genitalia to be of a male type more often than the other characters, for they are the last set of organs to be differentiated from the indifferent stage, and therefore the most likely of all organs to be male if it is really lateness of development of the testicular hormone which is responsible for “intersexuality.” But the facts are opposed to this interpretation; for the external organs are always of an essentially female type, though they are usually modified to some extent towards the male condition. It is important to note that the external genitalia are not simply of an embryonic type, but are of a definitely female type, usually with well developed labia. Of all my cases only one (No. 7) approaches the male condition at all closely in its external genitalia, and it is very far from resembling it ; for the projecting structure is quite in the wrong place for a penis and there is no sign of a prepuce,^* nor of a preputial diverticulum. The apparent penis is probably only an enlarged clitoris which in enlarging has carried the ventral labial commissure with it.

A question of some importance—though a very difficult one to decide — is whether these sex-intergrades are to be regarded as genetic males or females. As we have seen, they are regarded as genetic males by Crew. The evidence that this is so seems somewhat inconclusive, and is mainly founded on the fact that the gonads are usually definitely testes. But this is not a criterion, for free-martins, which are genetic females, sometimes have testes (Willier ¹¹ ) which resemble very closely the testes of sex-intergrades. It is true that spermatocytes have not been found in free-martin testes, but then they are not usually found in sex-intergrades. No. 8 is the only case of mine which shows them. It is not easy to account for the fact that spermatogenesis does not take place even in those testes (such as Nos. 3, 5, and 9) which are scrotal in position.

On account of the facts (1) that the ovary, when present, is a typical ovary with growing oocytes, (2) that the external genitalia are always essentially female, and (3) that the closest approach to normality (Nos. 1 and 2) is an approach to the female sex, I am inclined to regard sex-intergrades as masculinised genetic females.

The evidence from sex-ratio, given in Table I., is inconclusive. According to Wilckens ¹⁰  the normal sex-ratio in pigs is 111.8 ♂: 100 ♀.

A theory alternative to the one just enunciated is, I think, worth mentioning.

As Lillie points out⁵  there must be some mechanism whereby male embryos are protected from the sex-hormones of their mother. I suggest, very tentatively, that it is possible that it is the testicular hormone of the male embryo which normally neutralises the maternal ovarian hormone. (There is no reason to suppose that the embryonic testicular hormone is the same as the testicular hormone of the adult. See Aron ₁ on the histology of the interstitial cells in the embryonic and mature testis.) If for any reason the testicular hormone is produced too late or in insufficient quantity, the various organs might develop partly under the influence of the maternal sex-hormone. This theory is the same as Crew’s in considering the intergrade to be a modified male and as far as the poor development of the male organs is concerned ; but it differs from his in ascribing the development of female organs to the stimulus of the maternal hormone.

A corollary of this hypothesis is that the maternal ovarian hormone may normally play a part in the development of the genital organs of female embryos.

A point of difficulty in this theory is the essentially female type of external genitalia characteristic of sex-intergrades. Incidentally this is also a point of difficulty in connection with the free-martin, unless the external genitalia be supposed to differentiate independently of hormone control. Lillie overcomes the difficulty on the assumption that the external genitalia are the first to be differentiated, but this is contrary to fact.

From extirpation experiments and from pathological observations, it is well known that several of the ductless glands are concerned in the development and maintenance of a normal reproductive system. In particular the relation between the adrenals and sex has been carefully studied by Glynn, ⁸  who records cases of disease of the adrenal in “pseudo-hermaphroditism” in man.

To ascertain whether the abnormal condition of the reproductive system in pigs is associated with abnormality in any of the ductless glands, the pineal, pituitary, thyroid, and adrenals were removed from the youngest of the inter grades (No. 9, aged 10 weeks). They were found to weigh (in fresh condition) 0.019 gm., 0.151 gm., 1.888 gms., and 2.059 gms. respectively. The average weight of these glands at the age of 10 weeks has not yet been determined. No obvious signs of disease were observed, and the glands appeared normal histologically. It is possible that the abnormality may be caused by abnormality of one or more of the ductless glands in the embryo, but as yet there is no evidence that this is the case.

The sexual instincts of sex-intergrades appear usually to be male. Often intergrades attempt to copulate with females. In so doing they assume the attitude characteristic of the boar, and the clitoris becomes erected and protrudes.

I am informed by an intelligent pig-breeder that some of his sex-intergrades periodically showed signs of “heat,” although their instincts were male. The intergrades concerned were probably true hermaphrodites.

According to the New Hebrideans, the intergrades of their islands are subject to fits of rage, during the course of which their tusks become worn down in a characteristic manner. New Hebrideans will unhesitatingly designate one tusk as that of an intergrade and another as that of a boar. There is no doubt that certain of the tusks are worn down in a special way, and I see no reason to doubt their explanation. The fits of rage are occasioned by the sight of a female—presumably a female in “heat.”

I wish to record my thanks to the Trustees of the Percy Sladen Memorial Fund, who financed in part my visit to the New Hebrides, during which I first started to study sex-intergrade pigs; to Mr J. S. Huxley, for most valuable criticism; to Dr F. A. E. Crew, Dr H. S. Brown, Mr Alec Hobson, and Mr R. P. Redman for assistance in obtaining specimens; to the Rev. R. E. Tempest, for skilful interpretation of the native language; to Mr Frank Sherlock, for practical assistance; and especially to my wife for drawing many of the figures and for helping in other ways. I have also to thank Prof. E. S. Goodrich for encouragement and for providing the facilities of his laboratory.