Internal Genitalia Research Articles

Male Genitalia of Selected Genera of the Subfamily Melanoplinae (Orthoptera: Acrididae)

The morphology of the internal male genitalia of selected genera of Melanoplinae (Orthoptera: Acrididae) was studied. A detailed comparison of these structures was carried out, in an attempt to identify new characters that may be useful in analyzing relationships between the members of the subfamily. Twenty two genera were examined, mostly of North American distribution, using one exemplar species for each of them. Standard dissection and drawing techniques were followed. The epiphallus and the apical parts of the aedeagus were found to be the most important taxonomic characters. The genera Aptenopedes and Buckellacris were highly divergent from the rest of the melanoplines, while the close relationship between Appalachia, Dendrotettix and Podisma was confirmed by genital characters. Internal male genitalic characters did not provide significant support for many currently recognized tribes and subtribes, suggesting that there is a great need for reclassification in the subfamily. [Genitalia, morphology, Melanoplinae].

45,X/46,XY mosaicism: report of 27 cases.

There exist substantial differences between prenatally and postnatally diagnosed cases of 45,X/46,XY mosaicism. Ninety percent of prenatally diagnosed cases show a normal male phenotype, whereas the postnatally diagnosed cases show a wide spectrum of phenotypes. This 10% risk of an abnormal outcome in prenatally diagnosed cases requires further attention. The purpose of the present study is to provide more information on the postnatally diagnosed 45,X/46,XY mosaicism cases. To date, only a few series have been reported. An accurate diagnosis in these patients is essential not only to their follow-up, but also to providing appropriate genetic counselling and subsequent prenatal diagnosis to their parents. The clinical, cytogenetic, endocrinologic, histologic and molecular biological findings of 27 patients with 45, X/46,XY mosaicism are analyzed. The reported cases showed a wide spectrum of phenotypes as Turner syndrome, mixed gonadal dysgenesis (MGD), male pseudohermaphroditism (MPH) and apparently normal male. However, Ulrich-Turner stigmata were the most common features found in this series. Patients with MGD or MPH presented with various degrees of sex reversal such as hypospadias and/or abnormal internal genitalia. No correlation between the proportion of the 45,X/46,XY cell lines in the blood or the fibroblasts and the phenotype was found. Mild mental retardation was present in 4 of the patients and 2 patients showed signs of autism. Two major points are emphasized in this series: 1) the presence in 7 histologically analyzed streak gonads of a homogeneous 45,X chromosomal complement suggests that the invasion of the primitive genital ridge by a such a cell line may induce abnormal gonadal development; 2) 3 males, apparently normal at birth, developed late onset abnormalities such as dysgenetic testes leading to infertility, Ulrich-Turner stigmata, dysmorphic features, and mild mental retardation. These data indicate the importance of an accurate clinical and histologic evaluation of any patient presenting with 45, X/46,XY mosaicism.

Hypoplastic external genitalia in association with X;autosome chromosome translocation

Study Objective: To learn the relationship between X;autosome chromosome translocation and hypoplastic external genitalia. Background: An X;autosome translocation usually presents with phenotypic features similar to Turner syndrome. Participants: We present three female siblings and their mother with X;autosome translocation and hypoplastic external genitalia. Methods: Case presentation. Results: Three female siblings, ages 14, 16, and 18 years, presented for routine checkup. All had been seen in the past for short stature, learning disability, and other features similar to those seen in Turner syndrome. At time of presentation, all three had primary amenorrhea. On genital exam, each was found to have hypoplastic external genitalia with absent clitoris and labia minora. Pelvic ultrasound in all subjects showed normal but prepubertal uterus and ovaries. Two subjects have unbalanced translocations with karyotype 46,X,der(9)t(9;X)(q11.2;q22.3). This abnormal chromosome complement results in the loss of the short arm of the X chromosome and the gain of an extra copy of the long arm of chromosome 9. The third subject and her mother have balanced translocations with the karyotype 46,X,t(9;X)(q11.2;q22.3). Xinactivation studies showed skewed inactivation of the normal X chromosome in the balanced translocation carriers, while the two girls with the unbalanced karyotype had skewed inactivation of the translocation product. All subjects have growth hormone deficiency. The oldest sibling was able to menstruate regularly after estrogen/progesterone therapy. The other two patients are currently receiving growth hormone and are gaining height. Conclusion: X;autosome translocations may be associated with hypoplastic external genitalia but normal internal genitalia. Balanced carriers can be fertile. To our knowledge, the presence of hypoplastic external genitalia in association with X;autosome translocation has not been previously reported. This should be added to the possible causes of hypoplastic external genitalia.

Involvement of internal genitalia in female patients undergoing radical cystectomy for bladder cancer: a clinicopathologic study of 37 cases.

Radical cystectomy for invasive bladder cancer in female patients implies anterior pelvic exenteration. The necessity for routine removal of all internal female genitalia has not, as yet, been investigated. The present study was conducted to investigate the involvement of internal genitalia in these patients. Cystectomy specimens from 37 consecutive female patients with bladder cancer were examined for internal genitalia and urethral involvement. Clinical data were retrospectively collected from hospital charts. Thirty-four patients were available for postoperative follow-up. Of the 37 cases, 30 were transitional cell carcinoma (TCC), 4 squamous cell carcinoma, 1 adenocarcinoma, and 2 undifferentiated carcinoma. Uterine involvement was observed in only 1 case: TCC, stage D1, grade IV. All patients had normal ovaries and a normal vagina regardless of tumor site or stage; however, late ovarian and vaginal recurrences developed in one patient, in whom one ovary had been preserved. Sixteen percent of the patients had urethral involvement. We conclude that synchronous or metachronous involvement of female internal genitalia in bladder cancer is uncommon. Preservation of ovaries and vagina in young patients undergoing radical cystectomy may be considered under strict criteria.

STRATEGIES FOR RECONSTRUCTION AFTER UNSUCCESSFUL OR UNSATISFACTORY PRIMARY TREATMENT OF PATIENTS WITH BLADDER EXSTROPHY OR INCONTINENT EPISPADIAS

Purpose Following unsuccessful or unsatisfactory primary treatment in patients with the epispadias/exstrophy complex, the options for a surgical solution to preserve the upper urinary tract, to achieve complete continence, and to reconstruct the external and female internal genitalia are limited. We reviewed the records of the patients treated at our institution to determine a surgical compromise between ingenious operative constructions and patient desires, both of which are secondary to stabilization of renal function. Materials and Methods From 1967 to December 1997, 128 patients with bladder exstrophy/epispadias complex were treated, of 80 whom had received previous unsuccessful or unsatisfactory treatment. Of these patients 72 were followed for an average of 22.4 years after the first surgical intervention. There were 40 patients referred to our institution after primary bladder closure and bladder neck reconstruction, 10 after rectal bladder, 7 after ureterosigmoidostomy and 5 after incontinent diversion. Results At the latest followup 19 patients had a rectal reservoir, 38 an ileocecal pouch, 12 a conduit diversion and 3 an augmented Young-Dees procedure. The upper urinary tract remained stable in 95% of the renal units with rectal reservoir, 95% with ileocecal pouch, 96% with a colonic conduit and 100% with an augmented Young-Dees procedure. Day and night continence was achieved in 95% of the patients with a rectal reservoir and 97% of those with an ileocecal pouch were continent, whereas only 2 of the 3 patients with an augmented Young-Dees procedure were continent. Of the women 16 were satisfied with the cosmetic results and 6 delivered 8 children by cesarean section. Only 1 man was dissatisfied with the final cosmetic result. All adults but 1 engaged in sexual intercourse. Conclusions The first operative intervention in patients with bladder exstrophy/epispadias complex determines their fate. After failure of primary treatment, the upper urinary tract must be stabilized. In patients with severely impaired renal function the colonic conduit is our method of choice while in those with a normal or slightly dilated upper urinary tract and intact anal sphincter we performed a rectal reservoir. In the remaining patients an ileocecal pouch guarantees continence day and night. The results of genital reconstruction are satisfactory.

Antimullerian hormone

Antimullerian hormone (АМН) (also called Mullerian Inhibiting Substance) is the gonadal hormone. It is a member of the transforming growth factor-bb family of peptide growth and differentiation factors. АМН is produced in both male and female gonads - by Sertoli cells of the testis and granulosa cells of the ovaries. During the male embryogenesis АМН causes regression of Mullerian ducts, and testosterone stimulate the differentiation of wolffian system. During female embryogenesis, in the absence of АМН and testosterone, mullerian structures differentiate and develop into female internal genitalia and wolffian ducts regress.
 АМН continues to be produced by the granulosa cells of the ovary during the reproductive life of the women. АМН is known to inhibit resumption of meiosis in oocytes. Besides, АМН disturbs ovarian steroidogenesis: it decreases aromatase activity, leading to lowered estradiol production and hyperandrogenia in the follicle. АМН inhibits granulosa cells mitosis and decreases the number of LH-receptors on the granulosa cells. АМН is the antagonist of Epidermal Growth factor ( EGF) and might inhibit EGF-stimulated secretion of tissue-type plasminogen activator (tPA), which plays significant role in the ovulatory rupture of the follicle.
 Thus, АМН exerts inhibitory influence on all follicular components, including granulosa cells growth, steroidogenesis, oocyte maturation and follicle rupture process. It suggests, that АМН might play certain role in pathogenesis of chronic anovulation (polycystic ovaries syndrome).

The diagnostics and treatment of dishormonal mammal hyperplasia in uterine myoma patients

In gynecologic patients with internal genitalia diseases (endometriosis, uterine myoma) the frequency of mammal hyperplasia makes up to 60- 95%. The research aim was to study the effectiveness of conservative therapy with gestagens (norcolut, orgametril) application in benign hyperplastic mammal processes management in patients with uterine myomas. The effectiveness of gestagens application in patients with uterine myomas with coexisting dyshormonal mammal hyperplasia is proved.

Steroidogenic factor 1 (SF-1) is essential for endocrine development and functionProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic–pituitary–gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.

Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood.

Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0-10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and 21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to -2.6 standard deviation scores (SDS) (-6.3 to -0.6), P = 0.002, and -2.6 SDS (-4.8 to -0.5), P = 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated.

Development of the fetal uterus between 19 and 38 weeks of gestation: in-utero ultrasonographic measurements.

In-utero assessment of the internal female genitalia is important for determination of fetal gender in fetuses with suspected genital tract anomalies. We therefore measured fetal uterine transverse width and circumference from 19 weeks of gestation until term, using transvaginal and transabdominal high-resolution ultrasound techniques in order to establish nomograms. A prospective, cross-sectional study on 180 normal singleton pregnancies was performed. Data were obtained for 140 normal fetuses. The mean +/- SD uterine width and circumference were 12.9 +/- 4.1 mm (95% confidence interval 12.1-13.7), and 40.2 +/- 12.5 mm (95% confidence interval 37.9-42.5) respectively. Uterine size as a function of gestational age was expressed by the regression equations: uterine width (mm) = 12.9 + 0.7 x gestational age (weeks), and uterine circumference (mm) = 40.2 + 2.1 x gestational age. The correlation coefficients, r = 0.885 and r = 0.888, for uterine width and circumference, by gestational age respectively, were highly statistically significant (P < 0.001). A nomogram of uterine width and circumference per gestational week, and the 95% prediction limits were defined. The present data offer baseline measurements of the fetal uterus that may allow intrauterine assessment of the female genital tract and associated fetal gender.

Research on treatment of female idiopathic precocious puberty with combined traditional Chinese medicine and megestrol acetate

Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue.Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCM-WM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously.Results: After treated with TCM-WM for 2.7 years in average, the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48.5 ± 5.2 IU/L to 12. 2 ± 1.3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1.35 ± 0.09 to 0.65 ± 0.05 and predictive final height increased from 153.3 ± 0.5 cm to 158.5 ± 0.6 cm.Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients.

Hypoplastic External Genitalia in Association with X;Autosome Chromosome Trans Location.

<h3>Background</h3> X; autosome translocation usually presents with phenotypic features similar to Turner syndrome. We present three female siblings with X;autosome translocation and hypoplastic external genitalia. <h3>Methods</h3> Case presentation. <h3>Results</h3> Three female siblings, ages 14, 16, and 18 years, presented for routine check up. All had been seen in the past for short stature, primary amenorrhea, and other features similar to those seen in Turner syndrome. On genital exam, each was found to have hypoplastic external genitalia with absent clitoris and labia minora. Pelvic ultrasound in all subjects shows normal but prepubertal uterus and ovaries. Two subjects have unbalanced translocations with karyotype 46.X, der(9)t(9;X)(q11.2;q22.3). This abnormal chromosome complement results in the loss of the short arm of the X chromosome and the gain of an extra copy of the long arm of chromosome 9. The third subject and her mother have balanced translocations with the karyotype 46, X.t (9;X)(qI1.2;q22.3). X-inactivation studies show skewed inactivation of the normal X chromosome, while the two girls with the unbalanced karyotype had skewed inactivation of the translocation product. All subjects have growth hormone deficiency. The two older siblings were able to gain height and to menstruate regularly after growth hormone and estrogen/progesterone therapy. The youngest patient is still receiving growth hormone. <h3>Conclusion</h3> X;autosome translocations may be associated with hypoplastic external genitalia but normal internal genitalia. Balanced carriers can be fertile. To our knowledge. the presence of hypoplastic external genitalia in association with a X;autosome translocation has not been previously reported. This should be added to the possible causes of hypoplastic external genitalia.

The roles of steroidogenic factor 1 in endocrine development and function

The orphan nuclear receptor steroidogenic factor 1 (SF-1) was initially isolated as a key regulator of the cytochrome P450 steroid hydroxylases in adrenocortical and gonadal cells. Subsequent analyses of SF-1 knockout mice have expanded considerably our understanding of the roles that SF-1 plays in endocrine development. These SF-1 knockout mice lacked adrenal glands and gonads, with consequent male-to-female sex reversal of their internal and external genitalia. Thus, SF-1 is essential for the embryonic survival of the primary steroidogenic organs. They further exhibited impaired gonadotrope function and agenesis of the ventromedial hypothalamic nucleus, establishing that SF-1 contributes to reproductive function at all three levels of the hypothalamic-pituitary-gonadal axis. This report reviews experiments that have defined these critical roles of SF-1 in endocrine development, and highlights areas of ongoing investigation.

Breeding Soundness Examination of the Cow

Treatment or prevention of breeding problems is only possible after making the correct diagnosis. The accuracy of this diagnosis is based on:1. A detailed review of breeding records and compilation of an accurate history.2. A thorough evaluation of the entire reproductive tract.a. external inspection.b. evaluation of internal genitalia per rectum (palpation and ultrasound)c. vaginal examination.

The roles of steroidogenic factor 1 in endocrine development and function

The nuclear hormone receptor family—structurally-related transcriptional regulators that mediate the actions of steroid hormones, thyroid hormone, vitamin D, and retinoids—also includes orphan members that lack known activating ligands. One of these orphan receptors, steroidogenic factor 1 (SF-1), has recently been shown to play key roles in steroidogenic cell function within the adrenal cortex and gonads. SF-1 also contributes to reproductive function at all three levels of the hypothalamic–pituitary–gonadal axis. Key insights into these roles came from analyses of SF-1 knockout mice, which revealed adrenal and gonadal agenesis with consequent male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. This report reviews the data that have established SF-1 as a critical mediator of endocrine differentiation and function.

Candidate genes in complete and partial XY sex reversal: Mutation analysis of SRY, SRY-related genes and FTZ-F1

The sexual phenotype is established in three steps: (1) the sex chromosome constitution; (2) the differentiation of the gonads; and (3) the response of the internal and external genitalia to the hormones produced by the differentiated gonads. Errors that occur at any of these stages can result in defective sexual differentiation. Therefore the investigation of patients with abnormalities of testis development will help elucidate the mechanisms of sex determination and gonadal differentiation. It was in this way that SRY, the primary testis determining gene was identified. De novo mutations in SRY, result in gonadal dysgenesis by disrupting the DNA-binding activity of the SRY protein. However, only 20% of cases of gonadal dysgenesis, are explained by mutations in SRY or its flanking sequences. Therefore, there are several pieces to this puzzle yet to be discovered and it is hoped that mutation analysis of other genes implicated in gonadal development and differentiation may shed some light on aetiology of gonadal dysgenesis in the remaining 80% of cases.

La diferenciación sexual en vertebrados: hipótesis y teorías.

Se revisan cronológicamente las hipótesis y teorías que explican los procesos implicados en la diferenciación sexual en los vertebrados. Estas han asentado los precedentes teóricos y experimentales en el conocimiento de los mecanismos genéticos, celulares y moleculares a partir de los cuales se forma el testículo o el ovario, así como de los genitales internos y externos. Se analizan los puntos en común que hay entre las hipótesis y teorías descritas con base a evidencias experimentales. Se propone una sinopsis sobre la diferenciación sexual masculina en el ratón.

Origin, proliferation and differentiation of Leydig cells.

Mammalian sex determination involves complex interacting networks of cellular and hormonal signals leading to the development of male or female phenotypes. Three main sequential processes are involved: first, the establishment of chromosomal sex at fecundation (genetic sex); second, the development of the undifferentiated gonad into either testes or ovaries (gonadal sex); and third, differentiation of male or female internal and external genitalia (phenotypic sex). Male phenotype is controlled by two testicular hormones, the anti-Mullerian hormone (AMH) secreted by fetal Sertoli cells which induces regression of the Mullerian ducts, and testosterone produced by Leydig cells which induces differentiation of the Wolffian ducts into male reproductive organs, although conversion of testosterone into dehydrotestosterone is required for masculinization of the external genitalia. In the absence of testes, and therefore in the absence of both AMH and testosterone, the Wolffian ducts regress, creating a permissive environment for the differentiation of the Mullerian ducts and, thereby, female reproductive organs.

Central precocious puberty in girls: Internal genitalia before, during, and after treatment with long-acting gonadotropin-releasing hormone analogues

Pelvic ultrasonography was systematically performed on 33 girls with idiopathic central precocious puberty to investigate the impact of treatment with gonadotropin-releasing hormone analogues on female internal genitalia. All girls were treated with a long-acting gonadotropin-releasing hormone analogue (Decapeptyl Depot; Ferring Co., Copenhagen, Denmark) 75 μg/kg every 4 weeks. Before, during, and after treatment, pelvic ultrasonography was performed and ovarian and uterine volumes were calculated. The size of follicles > 5 mm were accurately measured. The results were related to a normative study of healthy Danish schoolgirls. Our data demonstrated that ovaries and uterus are enlarged in a significant number of girls (50%) with the diagnosis of central precocious puberty at the time of diagnosis. Median ovarian volume at time of diagnosis was 1.1 standard deviation scores (range –0.6 to 3.2 SD), median uterine volume was 1.8 standard deviation scores (range 0.0 to 3.5 SD). Within 3 months of treatment, both ovarian and uterine volumes decreased significantly ( p < 0.01) to normal values appropriate for age. Median ovarian volume after 3 months of treatment was 0.0 SD (range –2.4 to 1.5 SD); median uterine volume was 0.7 SD (range –0.6 to 4.1 SD). Ovarian and uterine volume remained within normal range (<2 standard deviation scores) after discontinuation of treatment. Follicles and macrocysts regressed during treatment. None of the girls' ovaries had a polycystic appearance during or after treatment with the gonadotropin-releasing hormone analogue. Our results confirmed pelvic ultrasonography as a reliable tool for investigation of internal genitalia in girls with precocious puberty and as a valid method for evaluation of the efficacy of treatment with gonadotropin-releasing hormone analogues. We suggest that repeated investigations be performed when evaluating treatment because the morphologic changes, including follicular maturation or regression, reflect ovarian stimulation or suppression. We found no evidence that girls with precocious puberty treated with long-acting gonadotropin-releasing hormone analogues have enlarged polycystic ovaries develop. (J Pediatr 1998;132:105-8)

Cerebellar hypoplasia, facial dysmorphism and internal abnormalities

Three female sibs had cerebellar hypoplasia, facial dysmorphism comprising a high forehead, lowset posteriorly rotated ears, a prominent upper lip and receding chin, and variable internal abnormalities. Two of the cases had deficient lobulation of the lungs, two had an atrial septal defect of the heart and developmental abnormalities of the urinary system or internal genitalia, one had holoprosencephaly. All had normal chromosomes. This syndrome does not seem to have been reported before and may be inherited in an autosomal recessive manner.