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Purpose: To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH)., Design: A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH and hCG)., Methods: Clinical and hormonal evaluations before and during gonadotropin stimulation in 19 CHH patients genotyped by Targeted Next Generation Sequencing for CHH genes; 16 patients underwent also semen analysis after gonadotropins., Results: A lesser increase in testicular volume after 24 months of induction was significantly associated with: (I) cryptorchidism; (II) a positive genetic background; (III) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of semen analyses, probably due to the low numerosity. Measures of body disproportion (eunuchoid habitus and difference between adult and target height: deltaSDSth), were significantly related to the: (I) age at the beginning of puberty induction; (II) duration of growth during the induction; (III) initial bone age. The duration of growth during induction was associated with previous testosterone priming and to partial forms of CHH., Conclusions: This study shows that a strong genetic background and cryptorchidism, as indicators of a complete GnRH deficiency since intrauterine life, are negative predictors of testicular response to gonadotropin stimulation in CHH. Body disproportion is associated with a delay in treatment and duration of growth during the induction, which is apparently inversely related to previous androgenization., (© 2021. The Author(s).)

Background This study aimed to evaluate the imaging findings of patients who underwent an abdominal and pelvic magnetic resonance imaging (MRI) due to primary amenorrhea. Methods The pelvic and abdominal images of 34 female patients (mean age 15.61 years, range 14-19 years) were retrospectively analyzed by a single radiologist blinded to the clinical and laboratory data of the patients (other than primary amenorrhea) to evaluate the etiology of primary amenorrhea. The anatomy and anomalies of the internal genital organs and other accompanying abdominopelvic anomalies were investigated. Results Gonadal dysgenesis was present in 14 patients (41.17%) and Müllerian duct anomalies (MDAs) were present in 20 (58.83%) (Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome in 13 [65%], distal vaginal obstruction [DVO] findings in five [25%], and obstructed hemivagina and ipsilateral renal anomaly [OHVIRA] syndrome in two [10%]). Seven patients with MRKH (53.84%) were of type 1 and six (46.15%) were of type 2. A total of eight additional anomalies (vertebral and renal) were detected, six in MRKH and two in OHVIRA syndrome cases. Endometrioma and hematosalpinx were observed in one of the five patients with DVO (5%). Conclusions Primary amenorrhea is a common symptom that affects both the physical and psychosocial status of individuals. Determination of the underlying etiology is the first step in planning treatment. The evaluation of internal genital organ anomalies involved in the etiology is important for sexual function and fertility. MRI is a non-invasive imaging modality that should be preferred in these cases as it provides detailed data about the anatomy and anomalies of internal genital organs due to its high soft tissue contrast resolution.

Pfaffia glomerata (Spreng.) Pedersen, popularly known as "Brazilian ginseng," is used as medicinal plant in Brazil to treat inflammatory diseases in general. Previous studies showed that its extract increases the nitric oxide (NO) levels. Knowing that NO downregulates steroidogenesis and that alterations in the action/production of androgens during perinatal life could alter testis development, the present studies sought to investigate the reproductive toxicity of Pfaffia glomerata on male mice exposed to hydroalcoholic extract in utero and during lactation. The present study shows that P. glomerata extract does not alter body weight, tubular diameter and testis function in male mice. Although a reduction in the testis weight was observed in the animals that received the highest dose directly in early post-natal life, our findings show clearly that P. glomerata may not act as an endocrine disruptor, and it is not an "antiandrogenic" compound that could lead to testicular dysgenesis syndrome., (© 2019 Blackwell Verlag GmbH.)

Progressive increases in the incidence of male reproductive disorders inclusive of hypospadias, cryptorchidism, poor semen quality, and testicular germ cell cancer (TGCC) have been observed in recent times. The central hypothesis of this study asserted that these disorders may all collectively signify testicular dysgenesis syndrome (TDS). This review aimed to provide evidence verifying the reality of TDS based on four key aspects: environmental endocrine-disrupting chemicals (EDCs), genetic factors, intrauterine growth disorders and lifestyle factors. Although TDS might result from genetic polymorphisms or aberration, recent evidence has highlighted links indicating the conditions associations to both environmental and lifestyle factors due to the rapid temporal changes in the clinical symptoms observed over recent decades. Based on our review of genetic and environmental factors, a key observation of our study suggested that there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. At present, current research has yet to elucidate the mechanisms of TDS, in addition to the lack of genuine consideration of a variety of potentially key factors and TDS mechanisms. In conclusion, our study revealed that environmental exposures owing to modern lifestyles are primary factors involved in the associated trends of the syndrome, which are capable of affecting the adult endocrine system via direct means or through epigenetic mechanisms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Somatic cell nuclear transfer (SCNT) provides an excellent model for studying epigenomic reprogramming during mammalian development. We mapped the whole genome and whole methylome for potential anomalies of mutations or epimutations in SCNT-generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is classified as 78, XY disorder of sex development (DSD). Whole genome sequencing revealed no potential genomic variations that could explain the pathogenesis of DSD. However, extensive but stochastic anomalies of genome-wide DNA methylation were discovered in these SCNT DSD dogs. Persistent abnormal hypermethylation of the SRY gene was observed together with its down-regulated mRNA and protein expression. Failure of SRY expression due to hypermethylation was further correlated with silencing of a serial of testis determining genes, including SOX9, SF1, SOX8, AMH and DMRT1 in an early embryonic development stage at E34 in the XY(DSD) gonad, and high activation of the female specific genes, including FOXL2, RSPO1, CYP19A1, WNT4, ERα and ERβ, after one postnatal year in the ovotestis. Our results demonstrate that incomplete demethylation on the SRY gene is the driving cause of XY(DSD) in these XY DSD dogs, indicating a central role of epigenetic regulation in sex determination.

Malouf syndrome is a rare congenital disorder involving the heart, genitalia, skin and skeletal characteristics. In the present study, we report on the sporadic case of a young female with dilated cardiomyopathy, hypergonadotropic hypogonadism, a small chin, bilateral blepharoptosis, marfanoid elongated fingers and hypothyroidism. Malouf syndrome may be caused by heterozygous mutations in the lamin A/C (LMNA) gene. Genetic analyses and autopsy were performed. In spite of the patient's features, sequence analysis of the coding region of the LMNA gene including exon-intron boundaries identified only one benign polymorphism: homozygous silent variant 1698C>T (H566). There is a possibility that the sequence analysis may have not detected intronic mutations or mutations in portions of the 5'- and 3'-untranslated regions, which would confirm the clinical diagnosis.

Isochromosome involving the long arm of X chromosome is a rare structural rearrangement of the X chromosome, leading to Gonadal dysgenesis. These patients present as phenotypic females with amenorrhea and growth failure. Often other associated features like endocrine abnormalities and skeletal deformities are found. They are chromatin positive cases and are only diagnosed by karyotyping. Hashimoto's thyroiditis is a rare association with isochromosome X.

Klinefelter's syndrome (KS) affects one in 600 men and Turner's syndrome (TS), one in 2500 women. These 2 diseases are the most sex chromosome disorders characterized by one extra X in the SK male (47XXY) and the loss of an X in the girls with ST (45 X). Their common characteristic is the gonadal dysgenesis, which is the main cause of male or female infertility. Called "the forgotten syndrome", KS is under-diagnosed because apart from the large size, there are no dysmorphic features, along with a great ignorance of cognitive and language disorders in children. There are often comorbidities that lead to diagnosis such as autoimmune diseases or metabolic syndrome. TS is often diagnosed by the short stature. Management of Turner's girls has profoundly changed with Growth hormone therapy. There is an international consensus for a better management of associated diseases such as ORL, cardiac, renal, hepatic, autoimmune and metabolic diseases. Prenatal diagnosis allows early detection and management of cognitive deficiencies and of associated diseases., (Copyright © 2011. Published by Elsevier SAS.)

Over the last decades there has been a dramatic increase in the incidence of some diseases associated with the male reproductive system, including poor semen quality, testicular cancer and congenital developmental abnormalities such as cryptorchidism and hypospadias, malformations of the urethra and scrotum respectively. Based on these observations one recurring theme is the concern that certain environmental chemicals and lifestyle related factors may play a role. Early fetal life is a particularly critical time period, when the endocrine system is established and organs are developing. Although available data does not yet allow recommending, evidence based, prophylactic and/or therapeutic measures to eliminate or reduce the possible negative impact of environment/lifestyle on the male reproductive capacity, it is prudent to limit exposures of people to hormonally active chemicals., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Researches on the testicular dysgenesis syndrome (TDS) have flourished in the recent decade, and a widely accepted view on its pathogenesis is that environmental endocrine disrupting chemicals (EDCs) act on Leydig cells and/or testicular Sertoli cells, resulting in abnormal development of the testis and leading to the symptoms of TDS. Molecular biological studies suggest a correlation of TDS etiology with insulin-like factor 3 (INSL-3), androgen receptor (AR), P27kip, WT-1 and Müllerian inhibiting substance (MIS). This review focuses on the progress in current researches on the etiology and mechanism of TDS.

It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity--the testicular dysgenesis syndrome--leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Two Drosophila melanogaster strains (Canton-S and ri-lines) for 20 generations were in the controlled terms of chronic irradiation with 3-dose rate (1,2 x 10(-8); 0,3 x 10(-8); 0,12 x 10(-8) Gy/c). The dynamics of hybrid dysgenesis frequency was explored for each generation of F1 descendants from Canton-S and ri-lines crossing. The gradual change of dose response of hybrid dispense depending on duration of irradiation of ancestors and dose rate was shown. The complex dynamics of hybrid dysgenesis frequency depending on irradiation duration of ancestors and dose rate was detected. The cumulative effect of the prolonged irradiation shows up as adaptation at the lowest dose rate and as exhaustion at the highest dose rate. Question comes into discussion about the features of transitional process and including of protective and adaptive reactions hierarchy at the conditions of radiation factor chronic action.

We have shown previously that deficient androgen action within a masculinization programming window (MPW; e15.5-e18.5 in rats) is important in the origin of male reproductive disorders and in programming male reproductive organ size, but that androgen action postnatally may be important to achieve this size. To further investigate importance of the MPW, we used two rat models, in which foetal androgen production or action was impaired during the MPW by exposing in utero to either di(n-butyl) phthalate (DBP) or to flutamide. Reduced anogenital distance (AGD) was used as a monitor of androgen production/action during the MPW. Offspring were evaluated in early puberty (Pnd25) to establish if reproductive organ size was altered. The testes, penis, ventral prostate (VP) and seminal vesicles (SV) were weighed and penis length measured. Both DBP and flutamide exposure in the MPW significantly reduced penis, VP and SV size along with AGD at Pnd25; AGD and organ size were highly correlated. In DBP-, but not flutamide-, exposed animals, testis weight was also reduced and correlated with AGD. Intratesticular testosterone was also measured in control and DBP-exposed males during (e17.5) or after (e21.5) the MPW and related to AGD at e21.5. To evaluate the importance of postnatal androgen action in reproductive organ growth, the effect of combinations of prenatal and postnatal maternal treatments on AGD and penis size at Pnd25 was evaluated. In prenatally DBP-exposed animals, further postnatal exposure to either DBP or flutamide significantly reduced AGD and penis size in comparison with prenatal DBP exposure alone. In comparison, rats exposed postnatally to testosterone propionate after prenatal vehicle-exposure showed considerable increase in these parameters vs. controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally.

Fertility among human beings appear to be on the decline in many Western countries, and part of the explanation may be decreasing male fecundity. A hypothesis has been put forward that decreasing semen quality may be associated with a testicular dysgenesis syndrome (TDS), a spectrum of disorders originating in early foetal life. TDS comprises various aspects of impaired gonadal development and function, including testicular cancer. A growing body of evidence, including animal models and research in human beings, points to lifestyle factors and endocrine disrupters as risk factors for TDS. We present our view of the emerging role of Leydig cell dysfunction with subsequent decreased testosterone levels in the pathogenesis of TDS.

The latest figures from the Cancer Registry of Norway show that Norway has the highest incidence rate of testicular cancer in the world. They also show that the incidence rate continues to increase, as it has for the last decades in the western world. The reasons for this increase, which might also be true for urogenital abnormalities in men and reduced sperm quality, are uncertain. Data suggest, however, that these anomalies originate in foetal life, and that contributing factors are genetic, pregnancy-related and environmental. The potential importance of environmental factors must be taken seriously, and the authorities must take action to strengthen the research in this area.

Summary The decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non-traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.

It has been hypothesized that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the so-called testicular dysgenesis syndrome (TDS). TDS was suggested to be a result of disruption of embryonal programming and gonadal development during foetal life and as aetiological factor, an impact of adverse environmental factors such as hormone disrupters, probably acting upon a susceptible genetic background, was suggested. Extensive studies considering the risk of TDS-related diseases in Denmark compared with Finland, showed higher sperm counts and lower risk of cryptorchidism and testicular cancer among Finns. However, when comparing these two populations, the question arises, to which degree this difference might be due to discrepancy in genetic background. A more obvious example of the impact of genetic factors on the risk of TDS concerns Afro-Americans having significantly lower incidence of testicular cancer when compared with Caucasians living in the USA. A yet unexplored scenario is a possible interaction between genetic and environmental/lifestyle-related factors, certain genotypes making individuals more susceptible to adverse exogenous exposures. Studying such interactions has biological, epidemiological and public health-related implications. It will help us to understand the background for the defects in male reproductive organs, facilitate proper design of epidemiological studies and add to identifying individuals susceptible to certain environmental and lifestyle-related hazards. Such 'susceptibility genes' need to be identified, those involved in the synthesis, action and metabolism of sex steroids being strong candidates.

The amount of research into endocrine disruption has exploded over the past decade and a re-evaluation of the state of research in this area is timely. There are debates about whether human male reproductive health is really declining and whether endocrine disrupting chemicals play any role in the perceived decline. Most data currently conclude that there are wide geographical variations in semen quality and in the incidence of testicular cancer, cryptorchidism and hypospadias. This review aims to give a brief overview of the issues surrounding the perceived decline in human male reproductive health and the importance of the hormonal environment for the development of the testis and reproductive tract. The consequences for the male reproductive tract of abnormal androgen levels or action are discussed with reference to environmental anti-androgenic compounds. The in vivo data on several anti-androgenic compounds that have been administered to pregnant rodents during the period of male reproductive tract development are assessed with attention to the effects on the male offspring. Finally, the data on in utero phthalate administration are discussed in detail to illustrate the similarities between the effects of some phthalate esters and the human male reproductive tract disorders which comprise testicular dysgenesis syndrome (TDS).

This review article summarizes the current knowledge on the development of gonadal dysgenesis in Turner syndrome. The degree of gonadal dysfunction is well correlated with the size of unpaired region of the sex chromosomes and is independent of the dosage of gene(s) on the sex chromosomes. Thus, it is deduced that sex chromosome aberrations result in meiotic pairing failure of homologous chromosomes, leading to accelerated oocyte loss and resultant gonadal dysgenesis. Although the underlying factor responsible for the oocyte loss remains to be determined, it is likely that activation of apoptotic mechanism to prevent the generation of abnormal gametes plays an essential role in the rapid oocyte degeneration.

In the Western world fertility rates are low and infertility is a major health problem. Unofficial statistics from Denmark reveal that about 6% of all Danish children are now born after assisted reproduction techniques, including in vitro fertilization, intracytoplasmic sperm injection, donor insemination or homologous insemination. However, there are no retrospective data on trends in fecundity (ability to conceive). We, and others, have focused on some aspects of adverse trends in male reproductive health such as the rising incidence of testicular cancer, low and probably declining semen quality, high and possibly increasing frequencies of undescended testes and hypospadias. Due to medical specialization and the different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, for instance paediatric endocrinologists, urologists, andrologists or oncologists. There is evidence that poor semen quality, testicular cancer, undescended testes and hypospadias are symptoms of one underlying entity, testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is the result of disruption of embryonal programming and gonadal development during fetal life. An endocrine disrupter hypothesis to explain the adverse trends has been proposed. It is recommended that future epidemiological studies on trends in male reproductive health should not focus on one symptom alone, but be more comprehensive and take all aspects of TDS into account., (Copyright 2003 S. Karger AG, Basel)

Disorders of androgen action are the main cause of male pseudohermaphroditism and include 5alphaR deficiency and androgen receptor defects. 5alphaR deficiency is characterized by female genitalia with some degree of masculinization, clitoromegaly, and severely bifid scrotum corresponding to the so-called pseudovaginal perineoscrotal hypospadias. At the onset of puberty, increased muscle mass, development of pubic hair, and phallic growth are associated with the acquisition of male gender identity. Normal or increased levels of testosterone and an elevated testosterone-to-dihydrotestosterone ratio after human chorionic gonadotropin stimulation testing suggest 5alphareductase deficiency, and the diagnosis can be ascertained by identifying the mutation in the 5alphaR-2 gene. Whatever the patient's age at diagnosis, psychological evaluation with 5alphaRD is vital. Androgen receptor defects encompass two clinical expressions: the complete and partial androgen insensitivity syndromes. Complete androgen insensitivity syndrome should be suspected at birth in the presence of inguinal hernia in a girl without genital ambiguity. At puberty, the sign of alert is primary amenorrhea with normal female phenotype and harmonious mammary development but no pubic hair growth. Partial androgen insensitivity syndrome covers a wide spectrum of undervirilized phenotypes ranging from clitoromegaly at birth to infertile men. In all cases, complementary investigations should include plasma testosterone and luteinizing hormone as well as androgen-binding capacity in cultured genital skin fibroblasts. Diagnosis is confirmed by identification of the androgen receptor gene mutation. Although patients with complete androgen insensitivity syndrome are raised as females, patients with partial androgen insensitivity syndrome should be managed according to age at diagnosis, response to treatment with exogenous androgens, and the presence of an androgen gene mutation. Gonadectomy in complete androgen insensitivity syndrome should be performed before puberty, and androgen substitution may improve the development of external genitalia in some patients with partial androgen insensitivity syndrome. Psychological follow-up is necessary.

An eighteen years old girl came from Ishargang, Mymensingh complaining of short stature, absence of development of breast, lack of menstruation and other secondary sex characters. She was found in infantile appearance with a height of 123 cm, body weight of 28 kg. She had short, broad, webbed neck, cuvitus valgus, absence of development of breast, axillary and public hairs with infantile external genitalia. Hormonal profile revealed high level of LH and FSH, low level of estrogens. Ultrasonography revealed uterine hypoplasia and ill defined gonadal streaks, Karyotype showed typical 45, X0 pattern. She was diagnosed as a case of gonadal dysgenesis due to Turner syndrome.

Unlabelled: A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%)., Conclusion: reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.

Turner syndrome is one of the most common chromosomal disorders. The incidence is about 1 on 2,500 till 1 on 10,000 living female young births. Short stature is the most common finding in patients with Turner syndrome. Besides short stature and gonadal dysgenesis, typical craniofacial and dental features are also present. Disturbance of the enchondral ossification results in abnormal craniofacial morphology. Oestrogen medication, to induce their puberty, and recombinant human growth therapy, to improve final height of these patients, are the most common treatment possibilities. It is the intention of this short paper to inform the dentist/orthodontist about the general aspects of the Turner syndrome. This information can be used in their treatment plan.

A hybrid dysgenesis syndrome occurs in Drosophila virilis when males from an established laboratory strain are crossed to females obtained from the wild, causing the simultaneous mobilization of several different transposable elements. The insertion sequence responsible for the mutant phenotype of a dysgenic yellow allele has been characterized and named Penelope. In situ hybridization and Southern analyses reveal the presence of more than 30 copies of this element in the P-like parental strain, whereas Penelope is absent in all M-like strains tested. Penelope contains one 2.5-kb-long ORF that could encode products with homology to integrase and reverse transcriptase. Northern analysis and whole-mount in situ hybridization show strong induction of a 2.6-kb RNA in the ovaries of dysgenic females that is expressed at very low levels in the parental strains or in the progeny from the reciprocal cross. Injection of Penelope-containing plasmids into preblastoderm embryos of an M-like strain results in mutant progeny caused by insertion of Ulysses and perhaps other transposons, suggesting that Penelope expression might be responsible for the observed dysgenesis syndrome and the simultaneous mobilization of other transposable elements.

A syndrome of abnormal genetic effects, resembling Drosophila hybrid dysgenesis, occurs in Ceratitis capitata when strains of different origin are mated. The pattern of abnormal traits observed appears to be the phenotypic expression of a complex interacting dysgenic system of inducer and suppressor effects; probably more than one system is activated in the crosses. This suggests that different systems of mobile elements occur in different strains and populations of C. capitata. Using a PCR primer specific to the ITR sequence of a deleted element, full length mariner elements were isolated from C. capitata, Ceratitis rosa, and Trirhithrum coffeae. Very high similarities were found in inter- and intraspecific comparisons of the elements. The majority of these elements contained deletions and frame-shifts. However, one clone Ccmar1.18, from C. capitata, was found to possess an uninterrupted ORF coding for 338 amino acids with approximately 60% similarity to the Mos1 element of Drosophila mauritiana. Database searches and phylogenetic analyses showed that the mariner elements isolated in the present study are representatives of Robertson's mellifera mariner subfamily. The copy numbers of the elements within each species are very different, ranging from about 10 in T. coffeae to 5000 in C. rosa.

Problem: Neonatal thymectomy (Tx) and estrogen (E2) administration disrupt the reproductive and immune systems of female mice. The current experiment examined the combined effects of the two procedures on ovarian function, performed in sequence, and in reverse sequence., Method: Groups of (C57BL/6J x A/J)F1 (B6A) female mice were given four daily injections of 20 micrograms estradiol-17 beta, either from 0 days to 3 days, or from 3 days to 6 days postpartum. In some groups this regimen was combined with thymectomy performed either prior to steroid injection (TX-3), or after steroid treatment (TX-4). Animals were sacrificed between 100 and 110 days of age then ovaries evaluated via light microscopy for dysgenesis and follicular cysts., Results: When E2 treatment followed Tx, the incidence of ovarian dysgenesis was unchanged (study 1, Tx + E2 = 60% ovarian dysgenesis; Tx = 63% ovarian dysgenesis) (study 2, Tx + E2 = 46% ovarian dysgenesis; Tx = 45% ovarian dysgenesis). In contrast, when E2 was given before Tx, ovarian dysgenesis did not occur (study 2, E2 + Tx = 0% ovarian dysgenesis; Tx = 46% ovarian dysgenesis). Ovaries from E2 + Tx animals were characteristic of ovaries from E2-injected animals without Tx., Conclusion: The results indicate that E2 injection prevents Tx-induced ovarian dysgenesis, suggesting E2-activation of an extrathymic pathway for thymus function.

Patients with ambiguous genitalia stand a far better chance of receiving a rapid diagnosis, appropriate replacement therapy, and functional surgical reconstruction than was the case even a decade ago. Although the etiologies of true hermaphroditism and mixed gonadal dysgenesis remain elusive, most gene defects in female pseudohermaphroditism or CAH have been pinpointed to the 21-hydroxylase gene. Incomplete masculinization has been found to be due to defects in the androgen receptor, 5 alpha-reductase, or enzymes in the pathway from cholesterol to testosterone. SRY point mutations have been implicated in 46XY pure gonadal dysgenesis. Retained müllerian ducts have been attributed to point mutations in the MIS gene; those with normal MIS levels should be expected to have receptor deficits. In utero diagnoses and treatment and diagnosis at the preimplantation stage may prove to be very important for the care of some of these patients, who may be potential candidates for gene replacement therapy. When necessary, surgical reconstruction can be done. If the child is to be raised as a female, clitoral recession, labioscrotal reductions and advancements, and vaginoplasties for exteriorization can be accomplished in early infancy as an extensive one-stage procedure. If patients are to be raised as males, then various types of hypospadias repair can be done, gonads can be replaced with prostheses, the prepenile scrotum can be reconstructed, and müllerian structures can be removed with the goal of preserving the vas deferens. Replacement therapy with glucocorticoids and mineralocorticoids must be precisely managed to permit proper growth, and testosterone, estrogen, and progesterone replacement must be carefully considered and managed. A most important element in the care of these patients is the psychological support that first the families and then the patient require. This must be delivered with sensitivity. The proper care of these complex patients requires that the physician be a scientist as well as a clinician and a skilled technician.

Development abnormalities of the female reproductive tract have a vast array of presentations and etiologies. This review outlines the etiologies, treatments and long-term follow-up of significant developmental anomalies of the female reproductive tract.

A ten year old boy was operated for left inguinal hernia at age four years. Male gender was confirmed by sex chromatin. Y corpuscle and male genotype in chromosomal studies, and testicular function was tested by normal testosterone serum levels before and after parenteral human chorionic gonadotropin stimulus. On a second operation, two structurally normal testes and was deferens coexisted with Müllerian structures (rudimentary uterus and two Fallopian tubes of normal histological features) were found. A diagnosis of uterus-inguinalis hernia was made. Deficiencies at Müllerian inhibiting factor's secretion, activity or receptors have been postulated to explain this anomaly.

Radioimmunoassay was used to study the blood content of LH and FSH in 116 patients aged 1 to 36 years with abnormalities of sexual development (false male hermafroditism, false female hermafroditism, true hermafroditism and gonadal dysgenesis). With a view of control the content of gonadotropins was measured in 92 subjects (33 females and 59 males) of the same age. The data were evaluated in accordance with the age and genetic sex of patients. It was shown that in health, the concentration of LH and FSH reflected the process of puberty, permanently growing until 18 years, whereas in patients, the age-related time course was less consistent. Unidirectional changes in the hormonal level (towards its rise) were common to all the forms of abnormal sexual development. In all the examinees, the pattern of changes in gonadotropic activity reflected the features of the formation of the neuroendocrine mechanisms by which the sexual system is controlled in ontogenesis.

Fourteen patients with Mixed Gonadal Dysgenesis who presented as infants or children are discussed. Gonadal asymmetry, and/or sex chromosomal mosaicism, as well as retained Mullerian Ducts characterize the anomaly. The dysgenetic testis may occur as the result of a cascade of development mishaps stemming from abnormalities of H-Y antigen expression or function that lead to abnormal differentiation of the indifferent urogenital ridge and, in turn, to aberrant production of Mullerian inhibiting Substance and testosterone. The latter two cause retention of Mullerian ducts and incomplete masculinization of the external genitalia. Absence of a second X chromosome may lead to the formation of a streak ovary, in which the dysgenetic testis may invoke formation of hilar and medullary cords. Neoplastic transformation, so characteristic of this group of patients, may result from unprotected germ cells and abnormally high and prolonged gonadotropin stimulation. Gonadoblastoma and seminoma-dysgerminomas are the tumors found in the gonads with the risk exceeding 50% as the third decade is approached. Laterality of the gonads in this anomaly remains an enigma. The gonads should be removed at birth if possible and the external genitalia repaired soon thereafter. These patients should be raised as females. The risk of neoplastic transformations must be considered at all stages of management.

The abnormalities of male sex differentiation are relevant from chromosomal abnormalities, male differentiation with inappropriate karyotype, true hermophroditism and male pseudohermaphroditism (MPH). We define MPH as incomplete masculinization of the external genitalia in subjects with normal 46 XY karyotype. Clinical phenotype of MPH is not characteristic: it will depend on the degree of the abnormality and to its timing during fetal life. The syndromes resulting in MPH are: dysgenesis of the fetal gonads, abnormalities of gonadotropin, deficiency of enzymes needed for the biosynthesis of testosterone, and abnormality of androgen target cells. Some of these syndromes occur sporadically whereas others happen with a specific aggregation. Clinical data suggest that several syndromes of MPH are transmitted as an X-linked recessive trait, although the deficiencies of the enzymes necessary for the biosynthesis of testosterone have been reported to be transmitted as an autosomal recessive trait.

Premature gonadal failure has been detected in phenotypically female dogs and cats with defective prenatal germ cell migration (ovarian aplasia), defective prenatal differentiation of the gonadal ridge into ovarian tissue (true hermaphroditism, male pseudohermaphroditism, ovarian dysgenesis in the presence of XO or XXX sex chromosome complements) or defective gamete maturation in the presence of primordial ovarian follicles (lymphocytic oophoritis, thyroid insufficiency). The most common of these is defective gonadal differentiation in animals with true hermaphroditism and failure of gamete maturation in thyroid insufficiency. A common clinical sign of premature gonadal failure in companion animals is failure to show a pubertal oestrus by 2 years of age. Diagnostic evaluation of such animals should include determination of the karyotype, plasma concentrations of LH and FSH and of thyroid hormones, gonadal histology, and gross evaluation of the Müllerian duct system at laparotomy.

Authors report a case of male pseudohermaphroditism reared as a female since birth. At abdominal exploration gonads showed the histologic pattern of immature testes, but were almost completely replaced by sex-cord mesenchymal tumors. It is remarked the opportunity of removing dysgenetic gonads earlier than usually suggested.

About one in 2000 newborn babies has an ambiguity of the external genitalia. The extent of the ambiguity gives no clue to the underlying aetiology. In this article the intersex disorders are discussed, with particular emphasis on the chromosomal and endocrine investigations.