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Regulation of luteinizing hormone-receptor and follicle-stimulating hormone-receptor messenger ribonucleic acid levels during development in the neonatal mouse ovary.

Normal gonadal development is dependent upon stimulation by the gonadotropic hormones, and it is likely that control of ovarian development is regulated by expression of gonadotropin receptors. In this study, quantitative changes in LH- and FSH-receptor mRNA levels were measured in the ovary during development in normal mice and in hypogonadal (hpg/hpg) mice, which lack circulating gonadotropins. The relative abundance of alternate transcripts encoding LH and FSH receptors was also determined. Results show that shortened transcripts of the receptors were abundant at all ages. Full-length transcripts of the LH receptor were not detectable until postnatal Day 5 although shortened transcripts encoding the extracellular domain of the receptor were present from birth. Between Days 5 and 7, LH-receptor transcript levels showed a marked increase in normal animals but no change in hpg/hpg animals. FSH-receptor transcripts encoding all domains of the receptor were detectable at low levels at birth, increased in concentration between Days 3 and 5, and peaked at Day 10. In hpg/hpg animals, FSH-receptor mRNA levels were normal up to Day 7 but failed to increase thereafter. These results show that early development of both LH- and FSH-receptor mRNA levels in the ovary is gonadotropin-independent. This coincides with early folliculogenesis to the primary stage. Further development of LH-receptor mRNA levels is gonadotropin-dependent although FSH-receptor mRNA levels continue to increase independently until early secondary follicles are present.

Animals↗

Timing of photorefractoriness in the European starling: significance of photoperiod early and late in the reproductive cycle.

In European starlings, as in many other birds inhabiting higher latitudes, gonads develop in response to the increasing daylengths in early spring. Later in the year, however, the hypothalamo-pituitary-gonadal axis becomes refractory to the previously stimulatory long photoperiods and the gonads regress in summer. The present study addresses the question of when during the gonadal growth phase photorefractoriness is determined. A 13-h photoperiod induces testicular development and subsequent testicular regression associated with refractoriness in male starlings. An 11-h photoperiod, in contrast, induces only testicular development, and photorefractoriness never develops. When starlings were transferred to an 11-h photoperiod, either 12 or 25 days following exposure to a 13-h photoperiod, their testes developed to full size, but remained large to the end of the experiment, i.e. refractoriness did not develop. The same was even true of most birds in a third group that were transferred to an 11-h photoperiod after 46 days of the 13-h photoperiod, when gonads had developed to near maximal size. These data show that, in contrast to some other species of passerine birds, the onset of photorefractoriness does not become fixed before the testes have undergone considerable development, and that the photoperiodic conditions experienced at the end of the testicular growth phase are still effective in determining the precise time of onset of photorefractoriness. It is suggested that this peculiarity of the starling is related to the fact that its gonadal development begins rather early in spring and, hence, under much shorter photoperiods than the other species studied.

Animals↗

Sex-specific and left-right asymmetric expression pattern of Bmp7 in the gonad of normal and sex-reversed chicken embryos.

A genetic switch determines whether the indifferent gonad develops into an ovary or a testis. In adult females of many avian species, the left ovary is functional while the right one regresses. In the embryo, bone morphogenetic proteins (BMP) mediate biological effects in many organ developments but their roles in avian sex determination and gonadal differentiation remains largely unknown. Here, we report the sex-specific and left-right (L-R) asymmetric expression pattern of Bmp7 in the chicken gonadogenesis. Bmp7 was L-R asymmetrically expressed at the beginning of genital ridge formation. After sexual differentiation occurred, sex-specific expression pattern of Bmp7 was observed in the ovary mesenchyme. In addition, ovary-specific Bmp7 expression was reduced in experimentally induced female-to-male reversal using the aromatase inhibitor (AI). These dynamic changes of expression pattern of Bmp7 in the gonad with or without AI treatment suggest that BMP may play roles in determination of L-R asymmetric development and sex-dependent differentiation in the avian gonadogenesis.

Animals↗

Ultrastructural aspects of gonadal morphogenesis in Bufo bufo (Amphibia Anura) 1. Sex differentiation.

The morphogenesis of gonads in Bufo bufo tadpoles was studied, and ultrastructural differences between sexes were identified. All specimens analyzed initially developed gonads made up of a peripheral fertile layer (cortex) surrounding a small primary cavity. Subsequently a central layer of somatic cells (medulla) developed. Both layers were separated by two uninterrupted basal laminae between which a vestige of the primary cavity persisted. During female differentiation, the peripheral layer continued to be the fertile layer. In males, the central layer blended into the peripheral layer and the basal laminae disappeared. The somatic cells of the central layer came into direct contact with the germ cells; this did not occur in females. Testicular differentiation continued with the migration of germ cells towards the center of the gonad. The somatic elements surrounding the germ cells appeared to play an active role in their transfer to the center of the gonad. The peripheral layer shrank and became sterile. Two basal laminae then re-formed to separate the fertile central layer from the peripheral sterile one. Germ cells have always been thought to perform a passive role in sex differentiation in amphibians. Following the generally accepted "symmetric model", the mechanism of gonad development is symmetrical, with cortical somatic cells determining ovarian differentiation and medullary somatic cells determining testicular differentiation. In contrast, we found that sex differentiation follows an "asymmetric" pattern in which germ cells tend primarily toward a female differentiation and male differentiation depends on a secondary interaction between germ cells and medullary somatic cells.

Animals↗

The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development.

We previously showed, using differential expression screening and in situ hybridization that Vanin-1, which encodes a glycosylphosphatidylinositol-linked membrane-associated pantetheinase, is expressed in a sex-specific manner during fetal gonad development in mice (Bowles, J., Bullejos, M., and Koopman, P. (2000) Genesis 27, 124-135). In the present study we investigate in detail the expression and regulation of Vanin-1 in the fetal testis. Vanin-1 is co-expressed with the transcription factors steroidogenic factor-1 (SF-1) and SOX9 in Sertoli cells and, at a lower level, with SF-1 in Leydig cells in developing testes. SF-1 is able to activate the transcription of the Vanin-1 promoter in in vitro reporter assays, and this activation is further augmented by SOX9. We found that SF-1 is able to bind to two sites in the Vanin-1 promoter, whereas SOX9 can bind to a single interposed site defined by DNA footprinting. Mutation of the SF-1 or SOX9 sites disrupts the binding of these factors and activation of transcription. The expression of Vanin-1 was abolished in Leydig cells of a mouse mutant lacking SF-1 in that cell type. Our findings account for the sex- and cell-type-specific expression of Vanin-1 in the developing mouse gonad in vivo, which we suggest is required to provide an appropriate environment for male germ cell development.

Amidohydrolases↗

Effects of ambient temperature on photo-induced prolactin secretion in three subspecies of white-crowned sparrow, Zonotrichia leucophrys.

We tested the effects of naturally relevant ambient temperatures (5, 20, and 30 degrees C) on photoinduced prolactin (PRL) secretion in three subspecies of white-crowned sparrow, Zonotrichia leucophrys. In all three subspecies, transfer from short to long days triggered an increase in plasma PRL typical of an avian seasonal breeder. In Z. l. gambelii, which breeds at high latitudes, temperature does not affect the rate of photoinduced gonadal maturation or luteinizing hormone (LH) secretion. In this subspecies, we found that changes in plasma PRL concentrations were similar in all temperature treatments. In Z. l. pugetensis, which breeds in the Pacific Northwest, high temperatures accelerate gonadal development in females but not males and does not affect LH secretion. In this subspecies, we found that like gonadal growth, photoinduced changes in PRL secretion in Z. l. pugetensis vary with ambient temperature in females but not males. In Z. l. oriantha, which breeds in alpine regions of the West, both males and females respond to temperature cues by modulating gonadal growth but not LH secretion. We found in Z. l. oriantha that ambient temperature affects PRL secretion in both sexes. These results suggest that PRL may be involved in the transduction of ambient temperature cues used to time reproductive development and the termination of seasonal breeding. Alternatively, temperature-mediated differences in plasma PRL may be a result rather than a cause of differences in gonadal development, since sex steroids affect PRL secretion in some species.

Animals↗

Sex chromosome and chromatin examination in gynecology.

Sex chromosome and chromatin examinations with hormone determinations were done on 41 cases seen at the gynecologic clinic suspected of having sexual developmental abnormalities. 22 (53.7%) had genetic, gonadal or hormonal abnormalities, including ovarian dysgenesis 9 cases, superfemale 1 case, XY pure gonadal dysgenesis 4 cases, 3 of whom had already developed gonadal malignancy, pseudovaginal perineoscrotal hypospadias 1 case, androgen insensitivity syndrome 2 cases and congenital adrenal hyperplasia 3 cases. The values and limitations of sex chromosome and chromatin examinations as well as the prevention of gonadal malignancy are discussed.

Adolescent↗

Germ cell nuclear antigen (GCNA1) expression does not require a gonadal environment or steroidogenic factor 1: examination of GCNA1 in ectopic germ cells and in Ftz-F1 null mice.

The germ cell lineage is first recognized as a population of mitotically proliferating primordial germ cells that migrate toward the gonadal ridge. Shortly after arriving at the gonadal ridge, the germ cells begin to initiate a commitment to gamete production in the developing gonad. The mechanisms controlling this transition are poorly understood. We recently reported that a mouse germ cell nuclear antigen 1 (GCNA1) is initially detected in both male and female germ cells as they reach the gonad at 11.5 days postcoitum (dpc). GCNA1 is continually expressed in germ cells through all stages of gametogenesis until the diplotene/dictyate stage of meiosis I. Since GCNA1 expression commences soon after primordial germ cells arrive at the gonadal ridge, we wanted to determine whether the gonadal environment was essential for induction of GCNA1 expression. By examining GCNA1 expression in germ cells that migrate ectopically into the adrenal gland, we determined that both the gonadal and adrenal gland environments allow GCNA1 expression. We also examined GCNA1 expression Ftz-F1 null mice, which were born lacking gonads and adrenal glands. During embryonic development in the Ftz-F1 null mice, the gonad and most germ cells undergo apoptotic degeneration at about 12.5 dpc. While most of the germ cells undergo apoptosis without expressing GCNA1, a few surviving germs cells, especially outside the involuting gonad clearly express GCNA1. Thus, although the Ftz-F1 gene is essential for gonadal and adrenal development, induction of GCNA1 expression in germ cells does not require Ftz-F1 gene products. The finding that germ cell GCNA1 expression is not restricted to the gonadal environment and is not dependent on the Ftz-F1 gene products suggests that GCNA1 expression may be initiated in the germ cell lineage by autonomous means.

Animals↗

Expression-based strategies for discovery of genes involved in testis and ovary development.

In recent years, strategies for gene identification based on differential gene expression have become increasingly popular, due in part to the development of microarray technology. These strategies are particularly well suited to the identification of genes involved in sex determination and gonadal development, which unlike the development of other organ systems, proceeds along two very different alternative courses, depending on the sex of the embryo. We have used a high-throughput, array-based expression screen to identify several genes expressed sex-specifically in developing mouse gonads. One of these, vanin 1, appears to play a role in mediating migration of mesonephric cells into the male genital ridge. Progress in characterizing other genes arising from the screen is discussed.

Animals↗

Human behavioral sex differences: a role for gonadal hormones during early development?

Evidence that gonadal hormones during prenatal and neonatal development influence behavior is reviewed. Several theoretical models of hormonal influences, derived from research in other species, are described. These models are evaluated on the basis of data from humans with either normal or abnormal hormonal exposure. It is concluded that the evidence is insufficient to determine which model best explains the data. Sexual differentiation may involve several dimensions, and different models may apply to different behaviors. Gonadal hormones appear to influence development of some human behaviors that show sex differences. The evidence is strongest for childhood play behavior and is relatively strong for sexual orientation and tendencies toward aggression. Also, high levels of hormones do not enhance intelligence, although a minimum level may be needed for optimal development of some cognitive processes. Directions for future research are proposed.

Adolescent↗

[Host-parasite interactions between Coccus hesperidum L. (Hom. Coccidae) and its parasite Coccophagus scutellaris Dalman (Hym. Aphelinidae)].

The eggs laid in the host gut will develop normally. The larva resulting from those eggs penetrate the hemocele through the gut wall. The structure of the cells near the entry point is not affected because of the continuous renewal of those cells. On the other hand, development of the ovaries is most seriously affected. In fact, ovogenesis is stopped and vitellogenesis slowed down. But this phenomenon is related to the initial level of ovary development. If the attack takes place when the host is young, the effect on the ovaries is more serious. In extreme cases gonad development is annihilated. Otherwise, the host will still be able to lay eggs, but its reproduction capacity is diminished. Factors reducing development of gonads or maintaining them at a juvenile stage are discussed.

Animals↗

Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia.

Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have the potential to differentiate into a variety of histological forms of overt testicular tumours. Analysis of cell surface antigens expressed by CIS cells found in the vicinity of pure and mixed tumours demonstrates that CIS cells are phenotypically heterogeneous. Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with their potential to give rise to different tumour types, and may be related to the developmental stage of the early germ cell which has undergone malignant transformation.

Adult↗

The matricellular protein SPARC is internalized in Sertoli, Leydig, and germ cells during testis differentiation.

The gene encoding the matricellular protein secreted protein, acidic and rich in cysteine (SPARC) was identified in a screen for genes expressed sex-specifically during mouse gonad development, as being strongly upregulated in the male gonad from very early in testis development. We present here a detailed analysis of SPARC gene and protein expression during testis development, from 11.5 to 15.5 days post coitum (dpc). Section in situ hybridization analysis revealed that SPARC mRNA is expressed by the Sertoli cells in the testis cords and the fetal Leydig cells, found within the interstitial space between the testis cords. Immunodetection with anti-SPARC antibody showed that the protein was located inside the testis cords, within the cytoplasm of Sertoli and germ cells. In the interstitium, SPARC was present intracellularly within the Leydig cells. The internalization of SPARC in Sertoli, Leydig, and germ cells suggests that it plays an intracellular regulatory role in these cell types during fetal testis development.

Animals↗

Syndromal (and nonsyndromal) forms of male pseudohermaphroditism.

The term sex determination refers to the genetic events that bring about male or female gonadal development; sex differentiation to all subsequent morphogenetic and physiological events that establish functional sexuality, sexual dimorphism and the secondary sexual characteristics. Virtually all of the steps of sex differentiation are under genetic control; consequently each one of them can fail as result of mutation of the corresponding genes. We shall be concerned with those genes and their mutations that cause pseudohermaphroditism in males and more rarely in females (with the exception of congenital adrenal hyperplasia). Special emphasis will be placed on Swyer, Denys-Drash, RSH, GBBB, campomelic and ATR-X syndromes, whose genes were recently identified.

Animals↗

Characterization of ovine SRY transcript and developmental expression of genes involved in sexual differentiation.

In mammals, the presence of SRY, the sex-determining gene located on the Y chromosome is required to induce the gonadal anlage to differentiate as a testis, whereas its absence leads to the development of an ovary. We report here the characterization by 5' and 3' RACE analysis of several SRY transcripts which are expressed in the ovine male developing gonads. These transcripts were not detected in any other fetal tissues and were expressed only in the genital portion of the urogenital ridge. The temporal profile of SRY expression analyzed by RT-PCR suggests that in the sheep fetus the role of SRY is not limited to initiating Sertoli cell differentiation as in mice. Indeed, SRY transcripts persist after the full differentiation of the testis. In addition to SRY, other genes are known to be involved in mammalian sex determination: Wilms' tumor gene WT-1, steroidogenic factor gene Ftz-F1 (SF-1) and anti-Müllerian hormone (AMH). We investigated the expression patterns of these genes by RT-PCR during fetal development in sheep gonads. Concerning WT-1 and SF-1, our results are consistent with those described in mice where the earliest expression was detected before the sexual differentiation in both sexes. In male, the ontogenesis of AMH transcription corresponds to the seminiferous cords formation (30 dpc). In female, we have observed the presence of SF-1 transcripts from the undifferentiated stage until birth. In addition, P450 aromatase expression is detected from 30 dpc and is correlated with the presence of 17-beta estradiol in sheep ovary. These data reveal significant differences between rodent and ruminant models concerning the sex-determining pathway.

Aging↗

[Characteristics of morphogenesis of rudimentary rat gonads transplanted into the testis].

The rat embryo (13 and 15 days of development) gonad germs of both sex, as well as isolated primary germ cells (PGC) have been transplanted into testes of mature animals of the same strain and investigated for 1.5 years. The isolated PGC are not able for further development and subjected to reduction. The gonad germs form analogues of the gonads with formation of definitive gonadal cells in 30 days. Further, degeneration of mature gonadal cells takes place. For realization of PGC ++cyto-differential processes and their stage-to-stage transformation into mature gametes certain interactions are necessary with concrete surrounding tissues that are at a strictly synchronized (with germ cells) stages of development.

Animals↗

Sexually dimorphic expression and hormonal responsiveness of steroidogenic Cyp genes during gonadal differentiation in mandarin fish.

Steroid hormones play a pivotal role in fish sex differentiation, yet the dynamic expression patterns of key steroidogenic enzymes during this process remain incompletely characterized. Here, we combined genome-wide identification, time series transcriptomes spanning gonadal development (5-360 days post-hatch), and multiple hormone treatment experiments (17α-methyltestosterone, estrone, and etonogestrel) to investigate the Cyp11, Cyp17, Cyp19, and Cyp21 subfamilies in mandarin fish (Siniperca chuatsi). Seven steroidogenic Cyp genes were identified, showing teleost-specific expansion, with one duplicated pair (cyp17a2 and cyp2u1) exhibiting strong purifying selection. Expression profiling revealed pronounced sexually dimorphic and stage-specific patterns: During female differentiation (20-30 days), cyp19a1a and associated genes were highly expressed, coinciding with ovarian differentiation; during male differentiation (30-60 days), cyp17a2 and related genes were upregulated, aligning with testicular development. Exogenous hormone treatments further demonstrated that these genes are dynamically responsive: cyp19a1a and cyp17a2 were highly responsive to androgenic and progestogenic treatments, and their expression changes correlated closely with gonadal sex reversal phenotypes observed histologically. Collectively, this study provides a comprehensive expression atlas of steroidogenic Cyp genes during gonadal differentiation and identifies key hormonally responsive candidates for sex control in aquaculture.

Animals↗

Neural structures associated with reproductive development and photoperiodic effects in male chicks (Gallus domesticus).

White Leghorn chicks given parasagittal knife cuts that isolated the hypothalamus from lateral connections displayed early maturation of the testes. When the operated chicks were subsequently exposed to a long-day photoperiod known to stimulate gonadal development, no additional increase in the size of the testes occurred. In contrast, controls demonstrated a marked development of the gonads that surpassed testes size of experimentals. An additional study was designed to determine whether the archistriatum, a telencephalic structure that has significant projections to the hypothalamus, may be involved in the earlier onset of puberty shown by knife-cut chicks. Three different sets of brain cuts were made that severed projections from the archistriatum to the hypothalamus. None of the knife cuts affected development of the gonads when the birds were examined six weeks after surgery. Two of the three sets of knife cuts, however, effected a significant reduction in food intake, and operated chicks also displayed a significantly lower body weight compared to controls (p less than 0.05).

Animals↗