True Hermaphroditism Research Articles

Primary amenorrhea: evaluation with MR imaging.

To determine the accuracy of magnetic resonance (MR) imaging in the evaluation of patients with a history of primary amenorrhea. Twenty-nine patients with primary amenorrhea underwent T2-weighted MR imaging in the axial and sagittal planes. Contrast material-enhanced and unenhanced T1-weighted MR imaging was performed in selected cases. MR imaging findings were correlated with surgical findings in 23 patients and with clinical findings in six patients. Surgical correlation was available in 14 of 17 patients with female anatomic anomalies (Mayer-Rokitansky-Küster-Hauser syndrome [n = 9], transverse vaginal septum [n = 3], imperforate hymen [n = 1], cervical agenesis [n = 1]), which confirmed MR imaging findings. In nine of 12 patients with congenital disorders of sexual differentiation (testicular feminization [n = 5], true hermaphrodite [n = 2], gonadal dysgenesis [n = 2]) who underwent surgical correlation, 13 of 16 (81%) gonads were correctly localized with MR imaging. Overall, there was excellent correlation between the classification of patients with MR imaging versus classification with the combination of surgical and laboratory findings (K = 0.88). MR imaging is useful in the work-up of patients who present with primary amenorrhea both for accurate diagnosis of pathologic conditions and for surgical planning.

True hermaphroditism: clinical aspects and molecular studies in 16 cases.

Although true hermaphroditism (TH) accounts for less than 10% of intersex patients, it stands as a diagnostic challenge and has allowed a better understanding of the mechanisms involved in sexual differentiation. In this paper we review the clinical and laboratory data as well as molecular biology findings on 16 TH patients followed up at the Pediatric Endocrine Unit, Instituto da Criança, Hospital das Clínicas. São Paulo University Medical School. They were of a mean age of 3 years 8 months and nine of them were black. All the patients had ambiguous external genitalia as the main complaint. The 46,XX karyotype accounted for 50% of the cases and the ovotestis was the most frequent gonad found (59%). In the eight TH patients with a 46,XX karyotype, the sex-determining region of the Y chromosome (SRY) was negative, posing an intriguing question about the testicular differentiation mechanisms involved in these cases. In 7/19 ovotestes, the ovarian portion of the gonad has been preserved, keeping open the possibility of fertility. The female sex option was made in 10/16 cases (62.5%) and three patients exhibited spontaneous puberty. The mechanism through which testicular tissue develops without SRY has not yet been completely clarified, suggesting the involvement of the X chromosome as well as autosomal genes in the process.

Sry gene detection in gonads of intersex patients using FISH.

A candidate gene for sex determination was localized within a 35 kb region of the Y chromosome immediately adjacent to the pseudoautosomal boundary. Here, we describe a study of Sry detection in the gonads of intersex patients including 5 male pseudohermaphrodite (MPH), 4 XX true hermaphrodite (TH) and each 1 mixed gonadal dysgenesis (MGD) and XX sex reversal, and in the clitoris of 3 female pseudohermaphrodite (FPH) by fluorescent in situ hybridization (FISH). Sry gene was observed in all cases of MPH and each case of MGD and sex reversal in contrast to bare expression in all cases of FPH and most of TH. To our knowledge, the Sry gene itself functions testicular determination in almost all intersex cases except true hermaphrodite, a distinguished type of intersex in a different pathogenesis. In addition, FISH might be useful to detect the translocated Sry gene and localize the signal with ease.

O-079 DNA analysis of the sex determining region on Y-related (SRY-related) autosomal gene SOX9 in subjects with true hermaphroditism (TH) (n=6) and Swyer syndrome (SS) with intact SRY (n=5)

O-079 DNA analysis of the sex determining region on Y-related (SRY-related) autosomal gene SOX9 in subjects with true hermaphroditism (TH) (n=6) and Swyer syndrome (SS) with intact SRY (n=5)

Hybridization and evolution inCardamine (Brassicaceae) at Urnerboden, Central Switzerland: Biosystematic and molecular evidence

Hybridization between two diploid (2n = 2x = 16) species ofBrassicaceae, Cardamine rivularis andC. amara, at Urnerboden, Central Switzerland, resulted in the rather unusual triploid hybridC. insueta (2n = 3x = 24), and later on in the amphiploidC. schulzii (2n = 6x = 48). The hybrid and the neopolyploid species colonized successfully some man-made biotopes. Plants ofC. insueta are mostly functional females with non-dehiscent anthers, but true hermaphrodite individuals with partly sterile pollen grains also occur within the population. Analyses of cpDNA and nuclear DNA permitted to establish the parentage of the hybrid: the maternal parent which contributed unreduced egg cells proved to beC. rivularis whereas the normally reduced pollen originated fromC. amara. The pronounced genetic variability inC. insueta revealed by isozyme and RAPD analyses, at variance with the polarized segregation, heterogamy and strong vegetative reproduction of the hybrid, is possibly influenced by recurrent formation ofC. insueta which party results from backcrosses betweenC. insueta andC. rivularis but may also proceed by other pathways. The amphiploidCardamine schulzii has normally developed anthers but its pollen is sometimes highly sterile. The surprisingly uniform genetic make-up of the new amphiploid species might be related to its possible monotopic origin and/or young phylogenetic age but should be further assessed. Site management seems to be very important to a further development of hybridogenous populations and their parent species. In conclusion, the evolution at Urnerboden is discussed in the context of the traditional concept of multiple plant origins.

Relevance of intersexuality to breeding and reproductive biotechnology programs; XX sex reversal in pigs

In pigs, the frequency of intersexuality ranges from 0.1 to 0.6%. Economic losses are significant and result from sterility, urogenital infections and downgrading of carcasses because of boar taint. To elucidate the genetic aetiology of pig sex reversion, 50 intersexes from a closed breeding herd were analysed. The majority have a 38,XX karyotype without Y chromosome sequences. Phenotypically, the animals range from true hermaphrodites to XX males with or without genital ambiguities. Analysis of crosses between parents of intersexes showed that the trait is inherited and caused by the same mutation in the Large White breed. Investigations are currently being carried out to isolate a genetic marker linked to intersexuality using genetic map of the porcine genome. Such a marker will be useful in eradicating the mutation in pig breeding herds and in permiting the isolation of the gene responsible.

Sigmoid colon vaginoplasty: a modified method.

To assess the technical feasibility and functional results of sigmoid colon vaginoplasty using a modified technique. Retrospective descriptive analysis. Referral centre. A method for creating an artificial vagina was applied in 13 women for the following indications: true hermaphrodite (n = 1), gender dysphoria (n = 2), Müllerian dysgenesis (n = 10). A method for sigmoid vaginoplasty was devised whereby transection of the inferior mesenteric artery proximal to the first sigmoid branch provides immediate mobility for the sigmoid colonic segment to reach the introitus (with adequate nourishment from the middle and inferior rectal vascular systems). Assessment of sexual function after a follow up period of 1 to 19 years. Twelve women reported a satisfactory result. Three of these were lost to follow up after one year, and the others report for regular assessment. Mild stenosis at the muco-cutaneous anastomosis, which may occur after failed perineal procedures, appears to be amenable to daily dilatations until the women become sexually active. In one woman the prosthesis had to be removed on account of severe pelvic floor fibrosis as a result of previous abdomino-perineal surgery at the age of seven. Another woman presented with a postcoital vesico-vaginal fistula after a previous McIndoe procedure; the tear at the base of the bladder was repaired and buttressed with a sigmoid vagina which is now functioning satisfactorily after 19 years. The creation of a sigmoid vagina which is vascularised by the middle and inferior rectal arterial systems appears to be an acceptable procedure for vaginal agenesis, acquired vaginal loss or sexual reassignment.

Crossed ectopia of ovotestis in a case of true hermaphroditism

True hermaphroditism is a rare form of intersex disorder. The authors report a case of true hermaphroditism with crossed ectopia of an ovotestis from the left to the right scrotum. The karyotype of the patient was 46,XX, without mosaicism. The majority of the ovotestis was comprised of testicular tissue. In other cases of human true hermaphroditism, descent of a pure ovary has not been noted to occur, despite the presence of the contralateral testis. Additionally, in congenital adrenal hyperplasia occurring in genotypic female subjects, pure ovaries do not descend into the scrotum despite the high level of androgens. Taken together, we believe that the demonstrated descent of mostly testicular ovotestes supports the idea that the testis produces a substance other than androgen that is important in guiding its descent.

Sex-determining genes on mouse autosomes identified by linkage analysis of C57BL/6J-YPOS sex reversal.

A powerful approach for identifying mammalian primary (gonadal) sex determination genes is the molecular genetic analyses of sex reversal conditions (that is, XX individuals with testicular tissue and XY individuals with ovarian tissue). Here we determined the number and chromosomal location of autosomal and X-linked genes that cause sex reversal in C57BL/6J (B6) mice carrying a Y chromosome of Mus domesticus poschiavinus origin (YPOS). B6 XYPOS mice develop either as females with exclusively ovarian tissue or as true hermaphrodites with ovarian and testicular tissue. In contrast, the YPOS chromosome is fully masculinizing on most other inbred strain backgrounds. B6-YPOS sex reversal appears to result from the incompatibility of the Sry (sex determining region, Y chromosome) allele carried on the YPOS chromosome with B6-derived autosomal or X-linked loci. We found strong evidence for the location of one gene, designated tda1 (testis-determining, autosomal 1), at the distal end of Chromosome (Chr) 4 and a second gene, tda2, in the central region of Chr 2. A third gene, tda3, on Chr 5 is implicated, but the evidence here is not as strong. We suggest that B6 alleles at these loci predispose XYPOS fetuses to ovarian tissue development, but no single locus or combination of loci is necessary and sufficient to cause sex reversal. The TDA proteins may regulate Sry expression or form complexes with the SRY protein to regulate other genes, or the tda genes may be activated or repressed by the SRY protein.

A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal.

Mutations in the gene SOX9 result in the syndrome of campomelic dysplasia (CD) which includes sex-reversal in 75% of 46,XY affected individuals. These mutations only affect a single allele of SOX9 suggesting a dominant mode of inheritance for this syndrome. Consequently, CD and autosomal sex reversal may result from haploinsufficiency of SOX9. The SOX9 gene maps to the long arm of human chromosome 17 and translocations in this region also result in CD. We report a family in which there were three affected patients, two of whom showed 46,XY sex-reversal. Interestingly, despite all three patients being heterozygous for a familial mutation in SOX9 (Insertion of a cytosine residue at nucleotide position 1096), their gonadal phenotypes varied widely. The proband was found to have 46,XY true hermaphroditism with ambiguous genitalia. The other two sibs were 46,XY and 46,XX, and both had bilateral ovaries with normal female genitalia. The somatic cells in both parents revealed wild-type SOX9 nucleotide sequences. However, mutational analysis of the SOX9 gene in the father's germ cells revealed they were mosaic for mutant and wild-type sequences. This family is particularly informative as it demonstrates that the same SOX9 mutation can produce very different 46,XY gonadal phenotypes. The range of gonadal morphologies observed may be explained by several possible mechanisms such as variable penetrance of the mutation, increased activity of the non-mutant SOX9 allele or stochastic environmental factors. These results also demonstrate that paternal germ cell mosaicism of a mutant SOX9 sequence can result in a CD phenotype amongst his offspring.

Females of four mole species of genus Talpa (insectivora, mammalia) are true hermaphrodites with ovotestes.

We studied the anatomical, histological, and genetic features of the sexual tract in four European mole species of the genus Talpa (Insectivora, mammalia): T. occidentalis, T. europaea, T. romana, and T. stankovici. All XY individuals had a normal male phenotype, whereas all XX individuals in all four species had features that identified them as intersexes. These individuals were nonetheless presumed to be functionally fertile females. Intersexuality was manifested mainly as gonadal hermaphroditism, with all females possessing bilateral ovotestes. The gonads were composed of a small portion of histologically normal ovarian tissue and a variably sized, generally large mass of disgenetic testicular tissue, accompanied by a small, rudimentary epididymis. The rest of the sexual tract was typically female, including oviducts, uterus, and vagina of normal appearance. Polymerase chain reaction (PCR) and Southern blotting analyses showed that the mammalian testis-determining gene SRY is present in males but not in females. Part of the conserved sequence of the mole SRY gene was cloned and sequenced after PCR amplification in two of the four mole species (T. occidentalis from Spain and T. romana from Italy). Sequences were identical in these two species and were very similar to those of the human and mouse SRY gene. Our findings constitute the first evidence of the existence of a genus-specific case of true hermaphroditism, probably due to a very ancient mutation that fixed in populations of the ancestral species from which contemporary moles evolved. The possible nature of this mutation is discussed with regard to the cytologic, histologic, and genetic features of the gonads in Talpa females.

Females of four mole species of genus Talpa (Insectivora, mammalia) are true hermaphrodites with ovotestes

Females of four mole species of genus Talpa (Insectivora, mammalia) are true hermaphrodites with ovotestes

Does Testosterone Diffuse Down the Wolffian Duct During Sexual Differentiation?

Purpose Sexual differentiation in gonadal dysgenesis is commonly asymmetrical. In patients with true hermaphroditism there may be an ovary and mullerian duct on 1 side, and a testis and wolffian duct on the other side. Such asymmetry suggests that testicular hormones only act locally at this early stage of sexual differentiation. We tested the hypothesis that testosterone reaches the wolffian duct by transport down the duct rather than by simple diffusion. Materials and Methods Mouse 14-day urogenital ridges were placed in organ culture and microinjected with testosterone-albumin-fluorescein isothiocyanate. Results At 17 hours fluorescence was found throughout the wolffian duct and by 48 hours it was maximal in the dilated caudal end. Conclusions Our results support the hypothesis that androgens may be transported along the wolffian duct. Secretion of testicular hormones into the wolffian duct may maintain hormone levels in the biologically active range.

Presence of the Y chromosome located sex determining region (SRY) gene in ovarian tissue of a 46,XX/46,XY true hermaphrodite: support for a threshold contribution of SRY carrying precursor cells in testicular morphogenesis.

Presence of the Y chromosome located sex determining region (SRY) gene in ovarian tissue of a 46,XX/46,XY true hermaphrodite: support for a threshold contribution of SRY carrying precursor cells in testicular morphogenesis.

True hermaphroditism and normal male genitalia: An unusual presentation

True hermaphroditism, the rarest form of intersex, is usually diagnosed during the newborn period in the course of evaluating ambiguous genitalia. As an exception, we present an unusual case of a 15-year-old boy with phenotypically normal male genitalia and bilaterally descended ovotestes, who was seen for evaluation of intermittent scrotal swelling and pain. Although rare, true hermaphroditism should be included in the differential diagnosis of apparently normal males presenting with similar complaints.

ETIOLOGIC DIAGNOSIS IN 126 CASES OF SEX AMBIGUITY

The complexity of human sex differentiation becomes manifest in the variety of diseases associated with sex ambiguity (SA). There are a few clinical centers especially dedicated to the managament of such patients, and hence, few large series have been published. We had the oportunity to evaluate 126 cases of SA. Among them, 57 (45.2%) were male pseudohermaphrodites (MPH), 35 (27.8%) were female pseudohermaphrodites (FPH), 23 (18.3%) had anomalies of gonadal differentiation (AGD), and 11 (8.71) exhibited other genital abnormalities. Among MPH, 36 were considered idiopathic, due to our impossibility to study androgen/receptor binding in cultured fibroblasts to diagnose partial androgen resistance, 11 were syndromic, there were 5 anorchias, 3 had complete androgen resistance, 1 had mullerian persistence and 1 5-alpha-reductase deficiency. Congenital adrenal hyperplasia was the main cause of FPH (24); there were also 6 syndromic cases and 5 idiopathic cases. Among AGD, there were 10 cases of true hermaphroditism, 8 Klinefelter syndromes, 3 mixed gonadal dysgenesis and 2 testicular dysgenesis due to sex chromosome aberrations. There were also 4 cases of balano-prepucial hypospadias, 3 of cryptorchidism, 3 incarcerated ovaries and 1 idiopathic microrchidism. Such a large series could only be achieved as a result of an interdisciplinary approach to SA over approximately 5 years.

A Case of True Hermaphroditism with Androgen Insensitivity

A phenotypically normal woman with a 46, XY karyotype was found to have a testis, an ovotestis, bilateral rudimentary uteri, and bilateral fallopian tubes. The endocrinological and pathological aspects of these findings are discussed.

XX true hermaphroditism in southern African blacks: exclusion of SRY sequences and uniparental disomy of the X chromosome.

A molecular investigation of 16 Bantu-speaking Black XX true hermaphrodites was undertaken in an attempt to determine the cause of the disorder. Y-specific sequences, including sequences mapping to the sex-determining region of the Y, were shown to be absent from lymphocyte tissue of all 16 patients tested. Y chromosome sequences were also absent from the ovarian and testicular components of both ovotestes of a single XX true hermaphrodite, thus excluding gonadal mosaicism involving Y chromosome sequences. Since there is evidence for Xp genes involved in testis determination/differentiation, uniparental disomy of the X chromosome was investigated in 14 XXTH families. Uniparental disomy was excluded in 12 of the 14 families, and isodisomy was excluded in the remaining two cases.

Molecular biologic analyses of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY

To investigate the mechanism of the formation of a tetragametic chimera with true hermaphroditism (46,XX/46,XY). Molecular biologic analyses. Outpatient clinic and laboratories of a university hospital. A true hermaphrodite with 46,XX/46,XY and the parents. MAIN OUTCOME ANALYSIS: Restriction fragment length polymorphism (RFLP) of the pseudoautosomal region on sex chromosomes. Whereas a normal diploid individual showed two bands, the true hermaphrodite showed four bands in the RFLP analyses. Evaluation of the molecular weights of the bands revealed two of them to be of maternal origin and the other two to be of paternal origin. The two cell lineages composing the true hermaphrodite are heterogeneous because those originated from the fertilization of two genetically different maternal haploid cells by two different spermatozoa.

Paediatric Applications of Anti-Müllerian Hormone Research

Anti-müllerian hormone (AMH), a member of the transforming growth factor family also called müllerian-inhibiting substance or factor, is produced by immature Sertoli cells and, in much smaller amounts, by postnatal granulosa cells. Its paediatric applications are essentially diagnostic. Measurement of AMH concentration in serum by an enzyme-linked immunosorbent assay does not require prior gonadal stimulation and is useful to detect the presence of testicular tissue and assess its function before puberty. The assay can easily differentiate between bilateral cryptorchidism and anorchia and discriminates between non-adrenal female pseudohermaphroditism and true hermaphroditism, although in the latter condition, the serum AMH concentration is usually low because of testicular dysgenesis. After puberty, AMH becomes low or undetectable, due to down-regulation of AMH production by testosterone. This does not occur in androgen-insensitive patients. A rare form of male pseudohermaphroditism, the persistent müllerian duct syndrome, characterized by the persistence of a uterus and tubes in otherwise normally virilized males, is due to defects in genes coding for AMH or its receptor. Measurement of serum AMH concentration discriminates between the two aetiological forms of the syndrome.