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PubMed2005

The tapeworm Ligula intestinalis (Cestoda: Pseudophyllidea) inhibits LH expression and puberty in its teleost host, Rutilus rutilus.

The tapeworm Ligula intestinalis occurs in the body cavity of its cyprinid second intermediate host, in this study the roach Rutilus rutilus, and inhibits host gonadal development. The mechanism by which infected fish are prevented from reproducing is unknown. Comparison of parameters, such as body length and weight, and condition factor and age, between infected and uninfected individuals, indicated only minor effects of parasitism on growth and condition. In contrast, seasonal gonadal development, as observed in uninfected fish, did not occur in infected fish, and gonads remained small and blocked at the primary oocyte stage in female roach. As immature ovaries and testes are still present, the parasite is presumed to act upon the brain-pituitary-gonadal axis of the fish to inhibit further development of reproductive organs. We investigated the Ligula/fish interaction at the level of the pituitary gland by determination of gonadotrophin (LH) content using a heterologous RIA for carp (Cyprinus carpio) LHbeta subunit. The results indicated that the pituitary glands of infected roach contained approximately 50% less LH than non-infected fish. After the cloning and sequencing of roach LHbeta subunit, we measured roach LHbeta mRNA levels by real-time RT-PCR. A corresponding 50% reduction in LHbeta mRNA pituitary levels was determined. These results reflect a significant and measurable effect of parasitism on the pituitary gland, and lend support to the hypothesis that excretory/secretory products released from the parasite interact with the brain-pituitary-gonadal axis of the fish host and thus inhibit gonadal development.

Animals↗
PubMed2002

SOX9 has both conserved and novel roles in marsupial sexual differentiation.

In addition to an essential role in chondrogenesis, SOX9 is a highly conserved and integral part of the testis determining pathway in human and mouse. To determine whether SOX9 is involved in sex determination in noneutherian mammals we cloned a marsupial orthologue and studied its expression. The tammar wallaby SOX9 gene proved to be highly conserved, and maps to a region of the tammar genome syntenic to human chromosome 17. Marsupial SOX9 transcripts were detected by RT-PCR in the developing limb buds and both the developing ovary and testis from the first sign of gonadal development through to adulthood. Northern blot, in situ hybridisation, and immunohistochemical analyses showed that SOX9 reaches high levels of expression in the developing testis, where it is confined to the Sertoli cell nuclei, and the brain. This is similar to the expression pattern seen in human and mouse embryos and is consistent with a conserved role for SOX9 in vertebrate brain, skeletal, and gonadal development. In addition, SOX9 was expressed in the developing scrotum and mammary gland primordium regions of the tammar up to the time of birth. SOX9 protein was also detected in the developing Wolffian duct epithelium in the male mesonephros. These previously undescribed locations of SOX9 expression suggest that SOX9 may play additional roles in the differentiation of the marsupial reproductive system.

Amino Acid Sequence↗
PubMed1990

Intersex and genital ambiguity.

Normal sexual differentiation in males and females is described. Discussion of disorders of abnormal sexual development is confined to those producing genital ambiguity. Genital ambiguity is further subdivided into disorders of gonadal development and disorders of fetal endocrinology. Disorders of gonadal development with abnormal sex chromosome constitution include those with and without sexual ambiguity. Only those producing sexual ambiguity, true hermaphroditism and mixed gonadal dysgenesis are discussed further. Disorders of fetal endocrinology are divided into female and male pseudo hermaphroditism. The main features of each are highlighted. A practical method of management of patients with ambiguous genitalia then follows.

Disorders of Sex Development↗
PubMed2005

Wnt4 expression in the differentiating gonad of the frog Rana rugosa.

Wnt4, a member of the Wnt family, is known to influence the sex-determination cascade. In mice having a targeted deletion of Wnt4, masculinization occurs in XX pups. Therefore, in addition to Sry, Wnt4 is also involved in sex determination in mice. In humans, a chromosomal duplication of the WNT4 causes feminization of XY-individuals. Thus, for better understanding of the mechanism of sex determination in vertebrates, it is necessary to examine the expression of Wnt4 at early gonadal development stages in non-mammalians. We first isolated the Wnt4 cDNA from the tetsis of the frog Rana rugosa. R. rugosa Wnt4 had a high similarity (>86%) at the amino acid level with zebra fish, chicken, mouse, and human Wnt4s. We next employed RT-PCR analysis to examine whether Wnt4 was expressed in a sexually dimorphic fashion at early stages of gonadal development in R. rugosa. Wnt4 was transcribed first in the embryos at the late gastrula stage, and its expression was maintained until the indifferent gonad differentiated into a testis or an ovary. Wnt4 expression in the differentiating gonad appeared in a non-sexually dimorphic pattern. The results, taken together, suggest that Wnt4 is highly conserved through evolution, and that its expression in the indifferent gonad takes place with no sexual dimorphism. Thus, Wnt4 is not a key factor to initiate the development of a testis or an ovary from the indifferent gonads in R. rugosa. However, this gene probably forms part of a gonadal-development pathway in this species.

Amino Acid Sequence↗
PubMed2001

Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses.

Gonad development in female sheep fetuses is thought to occur in a number of key stages. The aim of this study was to determine the effects of maternal undernutrition, applied at one or more of these critical stages, on fetal ovarian development. Groups of ewes (n = 11-19) were fed rations providing either 100% (high; H) or 50% (low; L) of energy requirements for live weight maintenance during selected 'windows' during gestation. Control ewes (HH and HHH) were fed the H ration from mating until they were killed at days 50, 65 (HH) or 110 (HHH) of gestation, whereas ewes of other groups were fed the L ration for the periods between day 0 and day 30 of gestation (LH and LHH), day 31 and day 50 or 65 of gestation (HL and HLH), day 65 and day 110 of gestation (HHL) or day 0 of gestation until the animals were killed (LL and LLL). At day 50 of gestation, there was no effect of nutritional treatment on mean fetal mass but compared with HH animals, mean fetal ovarian mass was significantly lower in HL (P < 0.05) and LL (P < 0.001) animals. At day 65 of gestation, there were significantly fewer germ cells (P < 0.05) at the resting, diplotene stage of initial meiosis in LL animals than there were in HH animals, indicating delayed germ cell maturation and onset of meiosis. Qualitative assessment of proliferative cell nuclear antigen immunostaining indicated that, at day 50 of gestation, staining was located predominantly in the germ cells, whereas by day 65 of gestation, staining was confined predominantly to somatic cells. Undernutrition in each one of these windows was associated with delayed ovarian follicular development (P < 0.05-0.001) as measured by development of the granulosa cell layer at day 110 of gestation. This study demonstrates that undernutrition before and during folliculogenesis can delay fetal follicular development.

Analysis of Variance↗
PubMed2004

Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice.

Congenital defects in genital and/or gonadal development occur in 1 in 1000 humans, but the molecular basis for these defects in most cases remains undefined. We show that the basic helix-loop-helix transcription factor Pod1 (capsulin/epicardin/Tcf21) is essential for normal development of the testes and ovaries, and hence for sexual differentiation. The gonads of Pod1 knockout (KO) mice were markedly hypoplastic, and the urogenital tracts of both XX and XY mice remained indistinguishable throughout embryogenesis. Within Pod1 KO gonads, the number of cells expressing the cholesterol side-chain cleavage enzyme (Scc) was increased markedly. Biochemical and genetic approaches demonstrated that Pod1 transcriptionally represses steroidogenic factor 1 (Sf1/Nr5a1/Ad4BP), an orphan nuclear receptor that regulates the expression of multiple genes (including Scc) that mediate sexual differentiation. Our results establish that Pod1 is essential for gonadal development, and place it in a transcriptional network that orchestrates cell fate decisions in gonadal progenitors.

Animals↗
PubMed1998

The effects of aromatase and 5 alpha-reductase inhibitors, antiandrogen, and sex steroids on Bidder's organs development and gonadal differentiation in Bufo bufo tadpoles.

Embryos of toads (Bufo bufo) were treated with aromatase (4-OHA) and 5 alpha-reductase (17 beta C) inhibitors, antiandrogen (CPA), estradiol-17 beta, testosterone, and 5 alpha-dihydrotestosterone in order to study the role played by sex steroids in the development and sex differentiation of gonads. Test compounds were administered to tadpoles in water and morphometric and cytometric analyses were carried out on histological sections of the cephalic Bidder's organ (a rudimentary ovary) and of the gonadal region. In Bidder's organs, the number and size of oogonia and oocytes were modified by the treatments. However, the female commitment of the Bidder's organ occurs independently from steroid treatments that lead to an acceleration or slackening of the processes of proliferation and differentiation of oogonia. 4-OHA and androgens caused various degrees of inhibition of ovarian differentiation, with gonads maintaining an undifferentiated condition. Estrogen provoked a shift of the sex ratio towards the female sex, yet slackened gonadal growth. 17 beta C accelerated ovarian differentiation in females while CPA enhanced gonadal differentiation in both sexes by promoting the germ and somatic cell proliferation. We suggest that sex hormones may have a local regulatory role in gonadal differentiation during early developmental stages. Furthermore, the strong tendency of Bidderian germ cells to develop in the oogenetic way regardless of sex genotype and steroid treatments, and the quantitative sex differences found in the control Bidder's organs and gonads, suggest that other factors (such as intracellular mechanisms) may be involved in the initial steps of the process of germ cell differentiation.

5-alpha Reductase Inhibitors↗
PubMed2006

The general and comparative biology of gonadotropin-inhibitory hormone (GnIH).

The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we identified a novel hypothalamic dodecapeptide that inhibits gonadotropin release in cultured quail pituitaries and termed it gonadotropin-inhibitory hormone (GnIH). To elucidate the mode of action of GnIH, we then identified a novel G protein-coupled receptor for GnIH in quail. The GnIH receptor possesses seven transmembrane domains and specifically binds to GnIH. The GnIH receptor is expressed in the pituitary and several brain regions including the hypothalamus. These results indicate that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release. To demonstrate the functional significance of GnIH and its potential role as a key regulatory neuropeptide in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited gonadal development and maintenance by decreasing gonadotropin synthesis and release. GnIH was also found in the hypothalamus of other avian species including sparrows and chickens and also inhibited gonadotropin synthesis and release. The pineal hormone melatonin may be a key factor controlling GnIH neural function, since quail GnIH neurons express melatonin receptor and melatonin treatment stimulates the expression of GnIH mRNA and mature GnIH peptide. Thus, GnIH is capable of transducing photoperiodic information via changes in the melatonin signal, thereby influencing the reproductive axis. It is concluded that GnIH, a newly discovered hypothalamic neuropeptide, is a key factor controlling avian reproduction. The discovery of avian GnIH opens a new research field in reproductive neuroendocrinology.

Amino Acid Sequence↗
PubMed1999

Migratory mechanisms of chick primordial germ cells toward gonadal anlage.

After appearing at the germinal crescent region, chick primordial germ cells (PGCs) migrate toward the presumptive gonads (pG) till stage 19 (Hamburger and Hamilton, 1951). This study seeks to elucidate the roles of passive and active factors in the PGC-migration, physical trapping of circulating PGCs by the capillary network and PGC attraction by chemotactic factor from presumptive gonads. Firstly, latex beads/pollens (the same size or larger than PGCs) were injected into the embryonic bloodstream at stage 13-19 (when PGCs are in the migrating and settlement phase to the presumptive gonad) in ovo in order to determine whether the PGCs passively reach pG. Most of such particles accumulated in the head region (60%), whereas the remainder did the same in the gonadal region (23% at the peak) at stage 16 when both the head and gonadal regions are rich in capillary plexus. After 3 days, most particles in the gonadal region were located at the angles of dorsal mesentery near the developing gonads where many extra-gonadal PGCs had been located, and a few particles were detected close to the gonad. These results suggest that one of the mechanisms of PGC-migration to the developing gonads is an autonomous trapping of PGCs by the capillary network quite close to the germinal epithelium (GE) and passive translocation by morphogenetic movement. Secondly, the attraction for PGCs by the gonadal anlage proper was examined in ovo using chick and quail embryos. Grafts of quail gonadal anlage containing gonadal epithelium and neighbouring mesenchymal tissue were excised from the quail embryo at stages 12 to 16 (staging by Zacchei, 1961). With the aims of eliminating the influence of surrounding tissue, the quail graft was ectopically transplanted into the posterior to the optic vesicle of 8 to 17 somite chick embryo from the point of a posterior region to the auditory vesicle by a fine tungsten needle under the illumination by the method of Hara (1971). Then the region posterior to the level of presumptive vitelline arteries was surgically excised in ovo. After a 48 hrs.-incubation, the host PGCs which lost their own gonadal anlage as a target organ accumulated in the transplanted quail gonadal anlage originating from the embryo at PGC-migrating periods. This result strongly suggested the presence of some attractive factor that may be emitted from the gonadal anlage proper. Furthermore, it was demonstrated that the PGCs in vitro showed no contact inhibition in relation to other PGCs or fibroblasts in their moving pathway.

Animals↗
PubMed2002

Influence of donor age on development of gonadal tissue from pouch young of the tammar wallaby, Macropus eugenii, after cryopreservation and xenografting into mice.

Ovaries from a marsupial, the tammar wallaby (Macropus eugenii), were grafted into a eutherian recipient at known stages of development to ascertain whether normal development would occur. Xenografted ovaries from pouch young < 20 days old, before the onset of meiosis, retained few germ cells and developed tubule-like structures reminiscent of seminiferous cords. Ovaries from 50-day-old pouch young, which contain primordial follicles, developed into antral follicles and corpora lutea within the eutherian host, and produced hormones that stimulated the reproductive tract of the host. The timing of onset of antrum formation and the progress of follicle development were advanced relative to the timing of events in ovaries in situ. Frozen-thawed ovaries from 50-day-old donors developed into preantral follicles, but at a reduced rate and number. This finding shows that gonads of a marsupial species can develop as xenografts in a eutherian, forming large antral follicles. Accelerated follicular development in xenografts provides a potentially valuable model for studying the factors that control follicle development. Assisted reproduction of endangered marsupials may also be feasible using follicles from pouch young grown as xenografts in a eutherian host.

Aging↗
PubMed1997

[Late sequelae of comprehensive antineoplastic therapy in children and adolescents with solid extracranial tumors. Effect on growth, pubertal development and gonadal function].

BACKGROUND: Modern treatment of oncological diseases increases markedly the chance of long-term survival and permanent recovery. Due to frequently highly aggressive treatment it is however associated with the risk of late sequelae in the surviving patients. Comprehensive care of patients includes therefore not only control of the neoplastic disease but also efforts of maximal improvement of the quality of life of the patients. In young subjects, in view of their long-term perspective, this problem is particularly important. METHODS AND RESULTS: In 32 patients (25 boys and 7 girls) with extracranial solid tumours without primary endocrinological symptomatology (m. Hodgkin, neuroblastoma, ganglioneuroblastoma, nephroblastoma, Ewings sarcoma and others) a single examination was made assessing height, body weight, grade of sexual maturation according to Tanner, in boys testicular volume by means of a orchidometer and 20 other anthropometric dimensions. The mean age at the time of examination was 16.5 +/- 4.1 years, the mean age at the onset of treatment 6.1 +/- 4.8 years. The patients height, -0.4 +/- 0.9 SD, differs from the Czech national standard (p = 0.025). Impaired growth was recorded in 12.5% patients and had heterogenous causes. The authors proved a negative effect of radiotherapy on the growth of the spine, most markedly in children subjected to irradiation of the abdomen and chest and a highly significant reduction of the testicular volume in boys after cytostatic treatment of m. Hodgkin. CONCLUSIONS: The results are consistent with studies made abroad and indicate the necessity of comprehensive long-term follow-up of somatic growth and development of the gonads in oncological child patients.

Adolescent↗
PubMed1999

The sexually dimorphic expression of androgen receptors in the song nucleus hyperstriatalis ventrale pars caudale of the zebra finch develops independently of gonadal steroids.

The development of sex differences in brain structure and brain chemistry ("brain sex") of vertebrates is frequently thought to depend entirely on gonadal steroids such as androgens and estrogens, which act on the brain at the genomic level by binding to intracellular transcription factors, the androgen receptors (ARs) and estrogen receptors (ERs). These hormone actions are thought to shift the brain from a monomorphic to a dimorphic phenotype. One prominent such example is the nucleus hyperstriatalis ventrale pars caudale (HVc) of the zebra finch (Poephila guttata), a set of cells in the caudal forebrain involved in the control of singing. In contrast with previous studies using nonspecific cell staining techniques, the size and neuron number of the HVc measured by the distribution of AR mRNA is already sexually dimorphic on posthatching day (P)9. No ARs or ERs are expressed in the HVc before day 9. Slice cultures of the caudal forebrain of P5 animals show that the sexually dimorphic expression of AR mRNA in HVc is independent of the direct action of steroids on this nucleus or any of its immediate presynaptic or postsynaptic partners. Therefore, gonadal steroids do not appear to be directly involved in the initial sex difference in the expression pattern of AR mRNA, size, and neuron number of the HVc. Furthermore, we demonstrate that the initial steroid-independent size and its subsequent steroid-independent growth by extension linearly with the extension of the forebrain explains 60-70% of the masculine development of the HVc. Thus, we suggest that epigenetic factors such as the gonadal steroids modify but cannot overwrite the sex difference in HVc volume determined autonomously in the brain.

Analysis of Variance↗
PubMed2006

Expression of serpinb6 serpins in germ and somatic cells of mouse gonads.

The serpin superfamily of serine protease inhibitors is implicated in the regulation of numerous physiological processes. In mice, Spi3/Serpinb6 has a broad tissue distribution. We have investigated the expression of Serpinb6 family members in embryonic and adult gonads. In male and female mice, Spi3/Serpinb6 and NK13/Serpinb6b were expressed in developing gonads and in both somatic and germ cells of adult gonads. By contrast, gonadal expression of Spi3C/Serpinb6c was sexually dimorphic and restricted to male germ cells and female somatic cells. These observations raise the question of the possible role(s) of the Serpinb6 family members in gonad development, gametogenesis, and/or fertilization.

Animals↗
PubMed1977

Y to X translocation in man.

Five new cases are added to the single published instance of Yq to Xp translocation(Xt) in man. It is shown that the anomaly can occur as a mutational event during meiosis, and can be inherited from a parent, but also that it can arise in a 47,XXY embryo. In individuals with 46,XXt karyotype the gonadal development, sexual differentiation, gonadal function and fertility are within the range of normal females. They do not present overt or discrete signs of virilisation. However, somatic stigmata, and more specifically short stature, are present in all patients. There is no uniform pattern of Xt inactivation which varies from random to apparently preferential inactivation. This phenomenon may be important for the better understanding of X-inactivation which for the Xt the authors believe is random but followed by differential proliferation of the resulting two types of cells.

Adolescent↗
PubMed2001

Characterization of steroidogenic factor 1 during sexual differentiation in a marsupial.

In eutherian mammals, such as mice and humans, steroidogenic factor 1 (SF1) plays important roles in the development of the gonad and in its steroidogenic activity. Marsupial and eutherian mammals have been evolving independently for at least 100 million years and so we were interested in comparing SF1 of a marsupial with that of eutherians. To this end, we have cloned SF1 from an Australian marsupial, the tammar wallaby. Although the amino acid sequence of SF1 is highly conserved among vertebrate species, tammar SF1 appears to have diverged less from the ancestral SF1 than have eutherian SF1 proteins. Tammar SF1 is expressed by both ovaries and testes on the day of birth, just prior to the onset of testicular differentiation, until at least 8 days after birth by which time the ovary also has begun to sexually differentiate. SF1 transcripts are localized predominantly to the pre-granulosa and Sertoli cells of the ovary and testis, respectively. In the testis SF1 transcripts are also present in the interstitial cells, although at a lower level than that which is observed in the Sertoli cells. SF1 is also transcribed in adult testis and ovary. In the adult ovary SF1 is expressed in the interstitial gland, and in the granulosa cells and theca interna of small to medium-sized antral follicles, but is not expressed in large antral follicles. Thus, although the structure of tammar SF1 is divergent from that of eutherians, its expression profile is similar, supporting a conserved role in gonadal development and steroidogenesis.

Amino Acid Sequence↗
PubMed1997

Suppressive effect of perinatal testes on the differentiation of fetal ovaries transplanted into adult males in the rat.

A 14 d ovarian primordium was transplanted with a fetal testis (13-18 d and 21 d of gestation) or a neonatal testis (15, 20, 30 and 45 d after birth) into the renal subcapsular position of an adult male rat. Two weeks after transplantation, transplants were examined as to the degree of ovarian and testicular differentiation. In the combination of a 14 d ovary and a 13 d testis, there were 3 types of result: either the ovary or the testis alone developed or both gonads developed well. Ovaries transplanted in union with 15-18 d testes did not develop, although the testes developed normally. Some ovaries in union with 21 d testes developed normally. In combination with infantile testes, the incidence of developed ovaries increased as the age of testes advanced. These results suggest that the 13 d fetal testes begin to suppress the development of cotransplanted 14 d ovaries, that 14-18 d fetal testes maintain such suppressive effects and that this effect gradually diminishes in infantile testes as they progress toward 45 d after birth.

Animals↗
PubMed1983

[Treatment of hypertensive forms of congenital adrenal hyperplasia].

The treatment of congenital adrenal hyperplasia (hypertensive forms) is based, as in the other forms of congenital adrenal hyperplasia, on corticosteroid therapy. The choice of drug, dosage, precocity, clinical and biological surveillance, are analysed in turn. The results on pubertal development, adult size, gonad development in the 11-betahydroxylase deficit type, are considered in the light of recent studies. The treatment of the 17-alpha-hydroxylase type is also based on the inhibition of glucocorticoid secretion. Results are satisfactory in the few cases published.

Adolescent↗