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PubMed1998

The basic helix-loop-helix, leucine zipper transcription factor, USF (upstream stimulatory factor), is a key regulator of SF-1 (steroidogenic factor-1) gene expression in pituitary gonadotrope and steroidogenic cells.

Tissue-specific expression of the mammalian FTZ-F1 gene is essential for adrenal and gonadal development and sexual differentiation. The FTZ-F1 gene encodes an orphan nuclear receptor, termed SF-1 (steroidogenic factor-1) or Ad4BP, which is a primary transcriptional regulator of several hormone and steroidogenic enzyme genes that are critical for normal physiological function of the hypothalamic-pituitary-gonadal axis in reproduction. The objective of the current study is to understand the molecular mechanisms underlying transcriptional regulation of SF-1 gene expression in the pituitary. We have studied a series of deletion and point mutations in the SF-1 promoter region for transcriptional activity in alphaT3-1 and L/betaT2 (pituitary gonadotrope), CV-1, JEG-3, and Y1 (adrenocortical) cell lines. Our results indicate that maximal expression of the SF-1 promoter in all cell types requires an E box element at -82/-77. This E box sequence (CACGTG) is identical to the binding element for USF (upstream stimulatory factor), a member of the helix-loop-helix family of transcription factors. Studies of the SF-1 gene E box element using gel mobility shift and antibody supershift assays indicate that USF may be a key transcriptional regulator of SF-1 gene expression.

Animals↗
PubMedDate not supplied

Effect of maternal overnutrition during pregnancy on pituitary gonadotrophin gene expression and gonadal morphology in female and male foetal sheep at day 103 of gestation.

The aim was to determine whether nutritionally mediated restriction of placental growth alters foetal body growth, pituitary gonadotrophin gene expression and gonadal development at Day 103 of gestation. Embryos recovered from adult ewes inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After transfer, adolescent ewes were offered a high (H, n=16) or moderate (M, n=12) level of a complete diet. Ewes were slaughtered at 103+/-0.2 days of gestation and foetal blood, brain, pituitary and gonads were collected. Mean placental weight was lower (P< 0.01) in H than in M groups but foetal weight and reproductive organ weights were similar. Maternal nutrition did not influence LHbeta or FSHbeta mRNA expression in either sex but FSHbeta mRNA expression was higher (P< 0.001) in female (n=11) than in male (n=17) foetal pituitaries. Mean foetal plasma gonadotrophin concentrations were not influenced by dietary intake in either sex. Plasma progesterone concentrations were lower (P=0.001) in foetuses derived from H compared with M intake dams. Compared with M foetuses (n=5), ovaries from H foetuses (n=6) had fewer primordial follicles (P< 0.05) and fewer follicles in total (P< 0.005). In contrast, maternal nutritional status did not influence either seminiferous cord or Sertoli cell numbers in male foetuses (H, n=10; M, n=7). It is concluded that high maternal nutrient intakes restricted placental growth and altered foetal ovarian follicular development prior to the end of the second third of gestation. The latter effect was independent of gonadotrophin secretion.Crown

Animal Nutritional Physiological Phenomena↗
PubMed1983

Antigonadal effects of timed melatonin infusion in pinealectomized male Djungarian hamsters (Phodopus sungorus sungorus): duration is the critical parameter.

To determine which parameter of the day/night pattern of pineal melatonin secretion is the critical component signaling daylength information in the Djungarian hamster, we have developed a method for giving timed sc melatonin infusions in pinealectomized juvenile males. When given for 12 h daily, as little as 10 ng melatonin (14 pg/min) consistently induced testicular regression within 12 days. However, 10 ng melatonin infused for 4 or 6 h daily did not inhibit gonadal development. The effects of these infusions on the reproductive system did not depend on the time of day at which melatonin was administered. In complementary experiments, the minimal daily infusion duration and the critical daylength for induction of testicular regression were determined. The critical length of infusion (7-8 h) was in close agreement with the estimated duration of melatonin secretion during the critical scotophase. These findings support the hypothesis that melatonin mediates the pineal-antigonadal effects of short day exposure in the Djungarian hamster. Furthermore, the data strongly suggest that duration is the feature of nighttime melatonin release that is most important for photoperiodic time measurement in this species.

Animals↗
PubMed2003

Male Japanese quails with female brains do not show male sexual behaviors.

During embryonic development, gonadal steroid hormones (androgens and estrogens) are thought to organize the sexual differentiation of the brain in the heterogametic sexes of higher vertebrates (males in mammals, females in birds). Brain differentiation of the homogametic sexes is thought to proceed by default, not requiring sex hormones for sex-specific organization. In gallinaceous birds such as the Japanese quail, female brain organization is thought to develop via estrogen-dependent demasculinization of a default male brain phenotype. We performed male donor-to-female host (MF), female-to-male (FM), male-to-male (MM), and female-to-female (FF) isotopic, isochronic transplantation of the forebrain primordium in Japanese quail embryos before gonadal differentiation had occurred; brain chimeras had a forebrain (including the hypothalamus) originating exclusively from donor cells. MM, FF, and MF chimeras all showed sexual behavior governed by the genetic sex of the host. In contrast, FM chimeras (genetically female forebrain, all other tissues genetically male) showed no mounting and only rudimentary crowing behavior. Although MM, FF, MF, and FM chimeras all showed host-typical production of steroid hormones during embryonic life, only FM chimeras were hypogonadal, had atypical low levels of circulating testosterone in adulthood, and showed reduction (crowing) or absence (mounting) of reproductive behaviors. Morphological features of the medial preoptic nucleus (a sexually dimorphic brain area) also were not male-like in FM males. These data demonstrate a brain-intrinsic, genetically determined component that organizes the sex-typical production of gonadal hormones in adulthood and call for a reevaluation of the mechanisms underlying brain sexual differentiation in other higher-vertebrate species.

Animals↗
PubMed2001

Hens, cocks and avian sex determination. A quest for genes on Z or W?

The sex of an individual is generally determined genetically by genes on one of the two sex chromosomes. In mammals, for instance, the presence of the male-specific Y chromosome confers maleness, whereas in Drosophila melanogaster and CAENORHABDITIS: elegans it is the number of X chromosomes that matters. For birds (males ZZ, females ZW), however, the situation remains unclear. The recent discovery that the Z-linked DMRT1 gene, which is conserved across phyla as a gene involved in sexual differentiation, is expressed early in male development suggests that it might be the number of Z chromosomes that regulate sex in birds. On the other hand, the recent identification of the first protein unique to female birds, encoded by the W-linked PKCIW gene, and the observation that it is expressed early in female gonads, suggests that the W chromosome plays a role in avian sexual differentiation. Clearly defining the roles of the DMRT1 and PKC1W genes in gonadal development, and ultimately determining whether avian sex is dependent on Z or W, will require transgenic experiments.

Animals↗
PubMed2004

Sex determination: insights from the chicken.

Not all vertebrates share the familiar system of XX:XY sex determination seen in mammals. In the chicken and other birds, sex is determined by a ZZ:ZW sex chromosome system. Gonadal development in the chicken has provided insights into the molecular genetics of vertebrate sex determination and how it has evolved. Such comparative studies show that vertebrate sex-determining pathways comprise both conserved and divergent elements. The chicken embryo resembles lower vertebrates in that estrogens play a central role in gonadal sex differentiation. However, several genes shown to be critical for mammalian sex determination are also expressed in the chicken, but their expression patterns differ, indicating functional plasticity. While the genetic trigger for sex determination in birds remains unknown, some promising candidate genes have recently emerged. The Z-linked gene, DMRT1, supports the Z-dosage model of avian sex determination. Two novel W-linked genes, ASW and FET1, represent candidate female determinants.

Animals↗
PubMed1985

Manipulation of the hypothalamo-pituitary gonadal axis in the juvenile rainbow trout: influence of pituitary transplantation and LHRH analogue treatment.

The effect of implanting an extra pituitary containing large amounts of gonadotropic hormone (GtH), combined or not with a luteinizing hormone releasing-hormone analogue (LHRHa) treatment, on GtH levels and gonadal development was investigated in juvenile host fish. The extrapituitaries were collected from mature spermiating fish or from immature fish treated with testosterone. In recipient males and females circulating plasma GtH levels increased following transplantation of both types of pituitaries. Elevated GtH levels presumably triggered steroid synthesis by the immature male gonad since pituitary GtH content was observed to accumulate in recipient males and not in females. However, the potency of the two kinds of pituitaries seemed different since spermatogenesis was stimulated only in some recipient males bearing a mature adult pituitary. This divergence could be due to a different sensitivity to endogenous gonadotropin-releasing hormone (GnRH). Only mature extrapituitaries might be highly sensitive to GnRH, as suggested by results obtained in juvenile host fish after LHRHa treatment. At the end of the 6-week experimental period, this LHRHa treatment stimulated spermatogenesis and induced a significant increase in pituitary GtH content only in juvenile hosts transplanted with a mature pituitary. Such a result was not observed in juvenile hosts submitted to a LHRHa treatment combined or not with the transplantation of juvenile testosterone-treated pituitary. However, previous works have shown that pituitaries collected from immature testosterone-treated fish are sensitive to GnRH. In the present experiment, the amount of GnRH-induced GtH release might have been too low to initiate spermatogenesis during the 6-week experimental period.

Animals↗
PubMed2000

Neoteny and progenesis as two heterochronic processes involved in paedomorphosis in Triturus alpestris (Amphibia: Caudata).

Current theories on the evolution of paedomorphosis suppose that several ontogenetic pathways have appeared according to different selective pressures. The aim of this study was to find out whether two distinct processes can lead to paedomorphosis in the Alpine newt, Triturus alpestris. In this respect, we compared age structures of paedomorphic and metamorphic individuals in two newt populations where the two forms lived syntopically. Whereas paedomorphosis resulted in a slower rate of somatic development in one population, it resulted in an acceleration of sexual maturation in the other population. These processes correspond to neoteny and progenesis, respectively. These results suggest that phenotypic plasticity can result from contrasted ontogenetic pathways between two populations of the same species. They give support to models that consider gonadic development as the target of selection under different environmental pressures.

Animals↗
PubMed1981

Cellular interrelationships in the human fetal ovary and testis.

Information on the cellular changes involved in human gonadal maturation has increased considerably in recent years with the introduction of special techniques for coordinating structural and functional analyses. An approach that appears to be particularly promising is the use of freeze-fracture techniques. Utilizing this method, we have demonstrated the formation of specialized intercellular junctions in the developing ovary and testis. Studies in several species have indicated similar findings which relate to the formation of the blood-testis barrier and the coordination of cellular activity involved in steroidogenesis. Further progress in understanding of maturational changes in the developing gonads will depend on continuing correlation of structural and functional changes in specific cell populations.

Cell Differentiation↗
PubMed1994

Histogenetic consideration of ovarian sex cord-stromal tumors analyzed by expression pattern of cytokeratins, vimentin, and laminin. Correlation studies with human gonads.

A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1 gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were immunohistochemically evaluated by means of cytokeratins of different molecular weight, vimentin and laminin with regard to the histogenesis of these tumors and to the embryogenesis of the sex cord and stroma of developing gonads. For comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5 postnatal testes, and 1 gonadoblastoma were also examined. The coelomic epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1) and vimentin. In fetal ovaries, the granulosa cells of primordial follicles express low molecular weight cytokeratins only and those cells of more maturing follicles did not express any cytokeratin or vimentin. In adult ovaries, the granulosa cells of primordial follicles coexpressed low molecular weight cytokeratins and vimentin, but those cells of more maturing follicles expressed vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and Leydig cells did not express any cytokeratins and vimentin. After that time, both cells expressed vimentin only throughout life. The rete ovarii and rete testis from fetal to adult life coexpressed both low molecular weight cytokeratins and vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood ages were surrounded by the laminin-positive basement membrane, however, the rete testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Evidence for a circadian oscillation in the gonadal response of the tropical weaver bird (Ploceus philippinus) to programmed photoperiod.

The effect of an asymmetrical skeleton photoperiod scheduleee was studied on the gonadal development in a tropical finch, the weaver bird (Ploceus philippinus). The schedul comprised a short nonstimulatory primary photoperiod of 6 hrs and a secondary much shorter lightperiod given as a 15-min light pulse at different times in the dark period. The light pulse 11 hrs after the basic period resulted in gonadal stimulation, while light pulse in contimuation with the basic period or 8, 14 or 21 hrs after the basicperiod was not stimulatory. The "photoinducible phase" was much more precisely outlined by shifting the birds from an 8-h to a 10-h pulse, and from an 11-h to 12-h pulse and was found to be very short, lasting about an hour falling between 11 and 12 hrs after the primary light period. The short photoinducible phase may be of an adaptive value since in the tropics the difference between the shortest and the longest daylength is also rather small (3 hrs and 15 min at Varanasi, 25degrees N). Clearly the weaver bird possesses a fine time-measuring device involving an endogenous circadian rhythm in photosensitivity. In nature, spermatogenesis in this bird also begins in March when the daylength exceeds 11 hrs (thus perhaps coinciding with the photoinducible phase). In rather small, photoperiod may not serve as a cue to trigger seasonal reproductive periodicity, it seems that photoperiod can act as a Zeitgeber for the initiation of spermatogenesis in the weaver bird at least.

Animals↗
PubMed1998

Normal reproductive and macrophage function in Pem homeobox gene-deficient mice.

Interaction between germ cells and the supporting somatic cells guides many of the differentiative processes of gametogenesis. The expression pattern of the Pem homeobox gene suggests that it may mediate specific inductive events in murine reproductive tissues. During gestation, Pem is expressed in migrating and early postmigratory primordial germ cells, as well as in all embryo-derived extraembryonic membranes. Pem expression ceases in the germline after Embryonic Day 14 in both sexes and then reappears postnatally in the supporting cells of the gonad. In mature mice, Pem is produced by testicular Sertoli cells during stages VI-VIII of spermatogenesis and transiently by ovarian granulosa cells lining periovulatory follicles. Despite this tightly regulated reproductive expression pattern, mice with a targeted mutation in Pem have normal fecundity, with no detectable alteration in extraembryonic testicular or ovarian development or function. We also show that Pem is expressed throughout embryonic and adult development in a subset of a tissue-specific class of macrophages, Kupffer cells, as well as in a localized fraction of cells in macrophage cell lines. Although the number of Pem-positive Kupffer cells increases in mice treated with lipopolysaccharide, loss of Pem does not detectably interfere with the cells' ability to induce iNOS expression, demonstrating this Kupffer cell function does not require Pem. No differences were observed between Pem-knockout mice in 129, C57BL6/J, or mixed genetic backgrounds. Together, these data show that Pem is dispensable for embryonic and postnatal development, gonadal function, and Kupffer cell activation, perhaps due to compensatory expression of a similar homeobox gene.

Animals↗
PubMed1988

Sex inversion as a model for the study of sex determination in vertebrates.

As a consequence of genetic sex determination, the indifferent gonadal blastema normally becomes either a testis or an ovary. This applies to mammals and to the majority of non-mammalian vertebrates. With the exception of placental mammals, however, partial or complete sex inversion can be induced in one sex by sexual steroid hormones of the opposite sex during a sensitive period of gonadogenesis. There is evidence that also during normal gonadogenesis in these species, in the XY/XX mechanism of sex determination testicular differentiation is induced by androgens, and in the ZZ/ZW mechanism, ovarian differentiation by oestrogens. In either case, the hormones may act via serological H-Y antigen as a morphogenetic factor. In contrast, in placental mammals including man, primary gonadal differentiation is independent of sexual steroid hormones, and factors directing differential gonadal development have not yet been conclusively identified. However, various mutations at the chromosome or gene level, resulting respectively in sex inversion or intersexuality, have provided clues as to some genes involved and their possible nature. In this context also, serological H-Y antigen is discussed as a possible factor acting on primordial gonadal cells and inducing differential growth or morphogenesis or both. The data available at present allow a tentative outline of the genetics of sex determination in placental mammals.

Animals↗
PubMed2005

Molecular cloning and expression in gonad of Rana rugosa WT1 and Fgf9.

Sry (sex-determining region on the Y chromosome) is required for testicular differentiation in mammals. In addition to Sry, other genes such as WT1, Fgf9, Dax1, Dmrt1 and Sox9 are widely accepted to be involved in the sex determination in vertebrates. However, the roles of these genes during sex determination still remain unclear in amphibians. This study was undertaken to examine the expression of WT1 and Fgf9 in the developing gonad of amphibians. We first isolated the WT1 cDNA from the frog Rana rugosa. Like WT1 in mice, R. rugosa WT1 showed 2 isoforms; i.e., one had an additional 3 amino acids, KTS, included between the third and fourth zinc fingers. However, 17 amino acids in exon 5 of mammalian WT1 could not be found in R. rugosa WT1, which is also the case in turtle and chicken. The mRNA of both isoforms (+KTS, -KTS) was detected in the lung, kidney and testis, but not in the ovary and muscle of adult frogs. The 2 isoforms were expressed first in the embryos at stage 23. Thereafter, the expressions remained constant in the gonad attached to mesonephros of both sexes during sex determination. We next isolated the R. rugosa Fgf9 cDNA encoding 208 amino acids. The amino acid sequence of Fgf9 had similarity greater than 92% with chicken, mouse and human Fgf9s, suggesting that Fgf9 is highly conserved among vertebrate classes. Fgf9 was expressed in the ovary of an adult frog strongly, but in the lung weakly. In contrast, the Fgf9 mRNA was hardly detected in the kidney, testis and muscle. Moreover, Fgf9 did not show a sexually dimorphic expression pattern during sex determination in R. rugosa. The results, taken together, suggest that both WT1 and Fgf9 are expressed in the indifferent gonad prior to sex determination without any difference in the expression between males and females. Thus, it seems unlikely that they are a key factor to initiate the divergence leading to testicular or ovarian differentiation in R. rugosa.

Amino Acid Sequence↗
PubMed1999

Mixed gonadal dysgenesis: a syndrome of broad clinical, cytogenetic and histopathologic spectrum.

Mixed gonadal dysgenesis (MGD) is an abnormality of sexual differentiation (ASD), which encompasses an heterogeneous group of different gonadal and phenotypic abnormalities. This study describes the main clinical features found in 16 patients with MGD, relating the clinical presentation with cytogenetic evaluation and histopathological findings. For purpose of this study, MGD was considered in those patients who fulfilled the following diagnostic criteria: 1) müllerian and/or wolfflan derivatives; 2) any of the following gonadal characteristics: a) bilateral intrabdominal or scrotal immature testicular tissue; b) intrabdominal or scrotal immature testicular tissue with contralateral streak gonad. Patients were selected from an ASD study which was carried out in Medical Genetic Unit of University of Zulia (UGM-LUZ), Maracaibo, Venezuela, from 1980 to 1997. The following information was extracted from the medical history at UGM-LUZ: age, gender which patient was reared, clinical presentation, cytogenetic evaluation, laparoscopic findings and gonadal biopsy. Sixteen patients fulfilled the diagnostic criteria and ranged in age from 1.2 to 39.4 years with an average of 12.65 years. Only 5 patients were reared as males. Twelve patients consulted for genital ambiguity. Chromosomal evaluation was as following: 8 patients with 45,X/46,XY mosaicism: 5 had a 46,XY normal male karyotype and the remaining patients: 46,XX; 46,XX/46,XY and 45,X/46,Xi(Xq) karyotypes, respectively. All patients showed müllerian derivatives and occasionally wolffian derivatives. Gonadal tumors were present in 2 patients. Molecular studies of genes that govern gonadal development are necessary for a better understanding of the wide heterogeneity present in MGD.

Adolescent↗
PubMed1983

An uncommon case of gonadoblastoma.

Gonadoblastoma occurs almost entirely in patients with pure mixed gonadal dysgenesis or in male pseudohermaphrodites. A report of a patient with monolateral gonadoblastoma who sought consultation for primary amenorrhea is presented. Telarche and adrenarche occurred spontaneously at age 12. No signs of clitoromegaly or hirsutism were present. Endoscopic examination and biopsy specimens revealed absence of uterus, monolateral gonadoblastoma and controlateral teratoma in normally developed gonads. Serum gonadotrophins, estrogens and progesterone levels showed a biphasic secretion pattern. 46, XX karyotype was found on peripheral blood cells, skin fibroblasts and ovarian tissue.

Adolescent↗
PubMed1976

Qualitative distribution of neutral lipids and phospholipids in Hymenolepis microstoma from the cysticercoid to the egg producing adult.

The distribution of neutral lipids and phospholipids in Hymenolepis microstoma has been studied using Fettrot, Sudan Black B, Sudan IV and copper phthalocyanin staining techniques. In the cysticercoid, neutral lipids are found in the outer membrane, the lining of the cysticercoid cavity, the tegument of the larval worm and the calcareous corpuscles. A decreasing gradient of phospholipids is found starting from the acellular layer, through the circular fibrous layer, the longitudinal fibrous layer, the adjacent dense zone and ending with the lining of the cysticercoid cavity. Phospholipids are also found in the calcareous corpuscles and the tegument of the larval worm. In the young adult (3 days p.i.) fat globules are first seen to accumulate in the last 2-3 proglottids. Until the 6th day p.i. they are found in the posterior third of the worm, surrounding developing gonads, but mostly concentrated along the transverse line. The mature proglottids contain fat, (a) in both granular and globular forms: in the folds of the uterus, sperm ducts, cirrus pouch and tegument (proximal cytoplasm), (b) in a diffuse form: in the vitellaria, ovary, testes and the tegument (distal cytoplasm). Pre-gravid and gravid proglottids show the largest fat globules. From the cleaving embryo to the fully developed oncosphere the concentrations of neutral lipids and phospholipids vary in form, intensity and location. In all strobilar forms of the parasite neutral lipids and phospholipids are found in the tegument and calcareous corpuscles. Although in H. microstoma lipid droplets are found in the excretory canals, all lipids in the proglottids are not absolutely waste products. From the results it would appear that they play a role in the maturation of gonads and transformation of the fertilized ovum to the oncosphere.

Animals↗
PubMed1998

Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.

The Wilms' tumor gene WT1 plays a key role in genitourinary development and subsequent normal function. Homozygous mutations of WT1 can be found in approximately 15% of Wilms' tumors. Furthermore, somatic heterozygous loss of WT1 is known to lead to cryptorchidism and hypospadias in males. A much more severe phenotype is seen in patients with Denys-Drash syndrome which results from heterozygous dominant-negative mutations of the gene. Characteristic features are mesangial sclerosis with early kidney failure, varying degrees of gonadal dysgenesis and high risk of Wilms' tumors. Here we show that a related disease, Frasier syndrome, characterized by focal glomerular sclerosis, delayed kidney failure and complete gonadal dysgenesis, is probably caused by specific intronic point mutations of WT1 that preferentially affect a CpG dinucleotide. Disruption of alternative splicing at the exon 9 splice donor site prevents synthesis of the usually more abundant WT1 +KTS isoform from the mutant allele. In contrast to Denys-Drash syndrome, no mutant protein is produced. The splice mutation leads to an imbalance of WT1 isoforms in vivo , as detected by RT-PCR on streak gonadal tissue. Thus, WT1 isoforms must have quite different functions, and the pathology of Frasier syndrome suggests that especially gonadal development may be particularly sensitive to imbalance or relative underrepresentation of the WT1 +KTS isoform.

Alternative Splicing↗