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Serotonin in golden hamster testes: testicular levels, immunolocalization and role during sexual development and photoperiodic regression-recrudescence transition.

Serotonin (5-HT) is found in the gonads and accessory reproductive organs of several species. The golden (Syrian) hamster is a seasonal breeder. Exposure of male adult hamsters to short days for 14 weeks results in a severe gonadal regression, while after a photoinhibition period of 22 weeks a spontaneous testicular recrudescence occurs. The aim of this study was to investigate the presence of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the gonads of golden hamsters, its immunolocation and its physiological role in the testis. The influence of age and photoperiod was also analyzed. Hamsters of 23, 36, 46, 60 and 90 days of age were kept in long photoperiod (LP: 14:10 h light/dark), and adult animals were exposed either to LP or to short photoperiod (SP: 6:18 h light/dark) for 14 and 22 weeks. Testicular parenchyma and capsule levels of 5-HT and 5-HIAA increased significantly at ages of 36 and 60-90 days, but decreased markedly during the exposure of adult hamsters to SP for 14 and 22 weeks. Mast cells were found exclusively in the testicular capsule. The testicular number of mast cells increased concomitantly with age, but decreased in adult hamsters exposed to SP. Mast and Leydig cells presented 5-HT-positive immunoreactivity. During sexual maturation as well as during the transfer of adult hamsters from LP to SP, the 5-HIAA/5-HT ratio showed the highest values in active adult animals, indicating that the increase in testicular 5-HT levels in adulthood is accompanied by an augment in 5-HT turnover. In vitro basal and hCG-stimulated testosterone production was significantly inhibited in presence of physiological concentrations of 5-HT. In conclusion, the present studies demonstrate the existence of 5-HT in mast cells and Leydig cells of hamster testes, as well as describe an inhibitory action of this neurotransmitter on gonadal testosterone production. Furthermore, the age-dependent and photoperiodic-related changes detected in testicular 5-HT levels suggest that this neurotransmitter might act as an important local modulator of the action of gonadotropins on steroidogenesis during sexual development and during the photoperiodic regression-recrudescence transition in the golden hamster.

Aging↗

Respiratory chain complex I is essential for sexual development in neurospora and binding of iron sulfur clusters are required for enzyme assembly.

We have cloned and disrupted in vivo, by repeat-induced point mutations, the nuclear gene coding for an iron sulfur subunit of complex I from Neurospora crassa, homologue of the mammalian TYKY protein. Analysis of the obtained mutant nuo21.3c revealed that complex I fails to assemble. The peripheral arm of the enzyme is disrupted while its membrane arm accumulates. Furthermore, mutated 21.3c-kD proteins, in which selected cysteine residues were substituted with alanines or serines, were expressed in mutant nuo21. 3c. The phenotypes of these strains regarding the formation of complex I are similar to that of the original mutant, indicating that binding of iron sulfur centers to protein subunits is a prerequisite for complex I assembly. Homozygous crosses of nuo21.3c strain, and of other complex I mutants, are unable to complete sexual development. The crosses are blocked at an early developmental stage, before fusion of the nuclei of opposite mating types. This phenotype can be rescued only by transformation with the intact gene. Our results suggest that this might be due to the compromised capacity of complex I-defective strains in energy production.

Animals↗

The gene csd is the primary signal for sexual development in the honeybee and encodes an SR-type protein.

Haplodiploid organisms comprise about 20% of animals. Males develop from unfertilized eggs while females are derived from fertilized eggs. The underlying mechanisms of sex determination, however, appear to be diverse and are poorly understood. We have dissected the complementary sex determiner (csd) locus in the honeybee to understand its molecular basis. In this species, csd acts as the primary sex-determining signal with several alleles segregating in populations. Males are hemizygous and females are heterozygous at this locus; nonreproducing diploid males occur when the locus is homozygous. We have characterized csd by positional cloning and repression analysis. csd alleles are highly variable and no transcription differences were found between sexes. These results establish csd as a primary signal that governs sexual development by its allelic composition. Structural similarity of csd with tra genes of Dipteran insects suggests some functional relation of what would otherwise appear to be unrelated sex-determination mechanisms.

Alleles↗

Aspergillus nidulans catalase-peroxidase gene (cpeA) is transcriptionally induced during sexual development through the transcription factor StuA.

Catalases, peroxidases, and catalase-peroxidases are important enzymes to cope with reactive oxygen species in pro- and eukaryotic cells. In the filamentous fungus Aspergillus nidulans three monofunctional catalases have been described, and a fourth catalase activity was observed in native polyacrylamide gels. The latter activity is probably due to the bifunctional enzyme catalase-peroxidase, which we characterized here. The gene, named cpeA, encodes an 81-kDa polypeptide with a conserved motif for heme coordination. The enzyme comprises of two similar domains, suggesting gene duplication and fusion during evolution. The first 439 amino acids share 22% identical residues with the C terminus. Homologous proteins are found in several prokaryotes, such as Escherichia coli and Mycobacterium tuberculosis (both with 61% identity). In fungi the enzyme has been noted in Penicillium simplicissimum, Septoria tritici, and Neurospora crassa (69% identical amino acids) but is absent from Saccharomyces cerevisiae. Expression analysis in A. nidulans revealed that the gene is transcriptionally induced upon carbon starvation and during sexual development, but starvation is not sufficient to reach high levels of the transcript during development. Besides transcriptional activation, we present evidence for posttranscriptional regulation. A green fluorescent protein fusion protein localized to the cytoplasm of Hülle cells. The Hülle cell-specific expression was dependent on the developmental regulator StuA, suggesting an activating function of this helix-loop-helix transcription factor.

Amino Acid Sequence↗

Aspects of the sexual development of Brahman versus Angus bulls in Florida.

Postweaning growth and reproductive traits were studied in 10 Brahman and 12 Angus bulls from 8 through 20 months of age. Brahman bulls reached puberty at 15.9+/-.4 months of age, weighed 432+/-16 kg, had a scrotal circumference (SC) of 33.4+/-1.2 cm, and plasma testosterone of 3.96+/-1.03 ng/ml. Breed differences in SC averaged over the entire study were not significant. However, the breedxday interaction (BxD) (P<.01) showed that, initially, the Brahman SC was smaller than the Angus SC; however, by the end of the study, the Brahman SC was larger than the Angus. When SC was adjusted for body weight, breed differences (P<.01) and BxD (P<.01) for SC/body weight (BW) reflected the later age and heavier weight at which the Brahman bull reached puberty. Plasma testosterone differed between breeds (Angus>Brahman, P<.01) and increased at a linear (P<.01) rate with age. There was no BxD in plasma testosterone. No breed differences in sperm concentration were observed. However, other semen traits were different (P<.01), i.e., rate of forward movement, sperm motility, total abnormalities and semen volume. A BxD (P<.01) was also evident for breed differences in these semen traits. Sexual development of the Brahman bull occurred at a later chronological age and in a nonparallel pattern to that of the Angus. Between animal variation in SC within the Brahmans and differences between this study and other reports suggest that differences in SC exist for various populations of Brahman bulls and should provide opportunities for progress in selection for this trait.

Journal Article↗

erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function.

Glial erbB-1 and erbB-4 receptors are key components of the process by which neuroendocrine glial cells control LHRH secretion and the onset of female puberty. We now provide evidence that these two signaling systems work in a coordinated fashion to control reproductive function. To generate animals carrying functionally impaired erbB-1 and erbB-4 receptors, we crossed Waved 2 (Wa-2+/+) mice harboring a point mutation of the erbB-1 receptor with mice expressing a dominant-negative erbB-4 receptor in astrocytes. In comparison to single-deficient mice, double-mutant animals exhibited a further delay in the onset of puberty and a strikingly diminished adult reproductive capacity. Ligand-dependent erbB receptor phosphorylation and erbB-mediated MAPK (ERK 1/2) phosphorylation were impaired in mutant astrocytes. Wa-2+/+ or double-mutant astrocytes failed to respond to TGF alpha with production of prostaglandin E2, one of the factors mediating the stimulatory effect of astroglial erbB receptor activation on LHRH release. Medium conditioned by Wa-2+/+ or double-mutant astrocytes treated with TGF alpha failed to stimulate LHRH release from GT1-7 cells. The LH response to ovariectomy was significantly attenuated in mutant mice in comparison with wild-type controls. Although the Wa-2 mutation affects all cells bearing erbB-1 receptors, these results suggest that a major defect underlying the reproductive defects of animals with impaired erbB signaling is a decreased ability of glial cells to stimulate LHRH release. Thus, a coordinated involvement of erbB-1 and erbB-4 signaling systems is required for the normalcy of sexual development and the maintenance of mature female reproductive function.

Animals↗

GABAergic activation inhibits the hypothalamic-pituitary-ovaric axis and sexual development in the immature female rat. Associated changes in hypothalamic glutamatergic and taurinergic systems.

The aim of the present studies was to assess, in immature female rats, the effect of the GABAergic system on the reproductive axis and on pubertal development. With this purpose we initially evaluated, in 30-day-old female rats, the effect of persistently enhanced GABAergic activity (aminooxyacetic acid (AOAA) 10 mg/kg per day i.p., during postnatal days 23-29) on hypothalamic gonadotropin-releasing hormone (GnRH) and amino acid neurotransmitter (AANT; glutamate or GLU, and taurine or TAU) concentrations, on circulating luteinizing hormone (LH) and estradiol levels, and on ovaric weight. In a second group of similarly treated rats, the date of vaginal opening (VO) was recorded. Complementary in vitro experiments (superfusion of anterior/mediobasal hypothalamic fragments obtained from rats aged 30 days) were performed to evaluate the effect of the short-term activation of the GABAergic system (by means of AOAA, muscimol or baclofen) on hypothalamic GnRH and AANT release. Prolonged treatment with AOAA led to a marked increase in hypothalamic gamma-aminobutyric-acid (GABA) concentrations (p<0.002), and to a significant decrease in hypothalamic GnRH and GLU content (p<0.05 and <0.02, respectively). Furthermore, treated animals showed diminished serum LH (p<0.05) and estradiol (p<0.005) levels, and a clear reduction in ovaric weight (p<0.002). Mean age at VO was 30. 8+/-0.6 days in control animals (range: 29-34 days), and 36.7+/-0.98 days in AOAA-treated rats (range: 33-40 days; p<0.0001). Acute treatment with AOAA resulted in a decreased GnRH and GLU output, and in an increased TAU release from superfused hypothalamic fragments. This effect was mimicked by the GABA-A and GABA-B agonists. Our results show that the activation of the GABAergic system during postnatal days 23-29 significantly restrains the hypothalamic-pituitary-ovaric axis, resulting in a clear-cut delay in sexual development. This can be attributed to the inhibitory effect exerted by GABA (acting on both GABA-A and GABA-B receptor subtypes) on GnRH release. Furthermore, the pharmacologic manipulation of the GABAergic system induces significant changes in the release of GLU and TAU, giving biochemical support to the existence of a physiological cross-talk between the excitatory and inhibitory AANT regulating GnRH release during the onset of puberty.

Aminooxyacetic Acid↗

Ontogenetic development, sexual differentiation, and effects of Aroclor 1254 exposure on expression of the arylhydrocarbon receptor and of the arylhydrocarbon receptor nuclear translocator in the rat hypothalamus.

Interaction of polychlorinated biphenyls (PCBs) with the aryl hydrocarbon receptor (AhR)/nuclear translocator (ARNT) system might interfere with the mechanisms controlling the sexual differentiation of the developing hypothalamus. The aim of this study was to evaluate the presence of AhR/ARNT in brain cells and the developmental profile of their expression in the hypothalamus of male and female rats during the perinatal period. Brain accumulation of the main PCB congeners after prenatal exposure to Aroclor 1254 and its influence on hypothalamic expression of AhR/ARNT was also assessed. The results show that: (a) AhR and ARNT are expressed both in neurons and in glia; (b) AhR expression progressively increases in the developing hypothalamus particularly in males, while ARNT is relatively constant in both sexes; (c) the prenatal administration of Aroclor to dams produces a differential accumulation of PCBs, depending on the chlorine atom number, and stimulates AhR expression only in the male hypothalamus. In conclusion, the developing male hypothalamus might be more sensitive to disrupting potential of PCBs.

Animals↗

Impact of disfiguring burn scars on adolescent sexual development.

It is popularly believed that disfiguring scars compromise the burned adolescent's ability to establish satisfactory dating relationships and to develop positive identities as sexually attractive people. The purpose of this study was to test that belief by obtaining information about the sexual behaviors and beliefs of adolescents who have disfiguring scars. Nineteen adolescents, ages 13 to 20 and at least 1 year postburn, completed a sexuality survey entitled What Young People Believe and Do--Revised. When compared with the available information, adolescents with disfiguring burn scars appear to have thoughts, feelings, and behaviors that are similar to those of nonburned adolescents. The severity of disfigurement as measured by numbers of affected body areas does not seem to be related to the sexual behaviors of the teenagers in this sample.

Adolescent↗

Reactive oxygen species generated by microbial NADPH oxidase NoxA regulate sexual development in Aspergillus nidulans.

NADPH oxidases (Nox) have been characterized as higher eukaryotic enzymes used deliberately to produce reactive oxygen species (ROS). The recent discovery of new functional members of the Nox family in plants and animals has led to the recognition of the increasing importance of ROS as signals involved in regulation of diverse cellular processes such as defence, growth and signalling. Here, we address the role of NADPH oxidase-generated ROS in the biology of the filamentous fungus Aspergillus nidulans. We characterize the noxA gene and show that it encodes a member of a novel NADPH oxidase subfamily ubiquitous in lower eukaryotes. Deletion of noxA specifically blocks differentiation of sexual fruit bodies (cleistothecia), without affecting hyphal growth or asexual development. Accordingly, the noxA gene is induced during sexual development, peaking at the time of cleistothecia differentiation and in parallel with the hülle cell-associated catalase peroxidase gene cpeA. This expression pattern is not dependent on transcription factors SteA and StuA, which are essential for cleistothecia formation. In contrast, noxA-dependent premature sexual development correlates with noxA derepression in DeltasakA null mutants, connecting stress MAPK signalling to the regulated production of ROS. Using a nitroblue tetrazolium (NBT) assay to detect superoxide, we found that hülle cells and cleistothecia initials produce superoxide in a process inhibited by NADPH oxidase inhibitor DPI and markedly reduced in DeltanoxA mutants. Furthermore, using H2DCFDA, we detected that H2O2 and possibly other ROS are generated in a NoxA-dependent fashion, mainly in the external walls from cleistothecia initials. The essential role of NoxA-generated ROS in A. nidulans sexual differentiation and the presence of one or two noxA homologues in all analysed filamentous fungi suggest that NADPH oxidase-generated ROS play important roles in fungal physiology and differentiation.

Amino Acid Sequence↗

The hormonal control of sexual development.

The formation of the testis or ovary is a critical step in development. The pioneering studies of Professor Alfred Jost showed that the hormones produced by the embryonic rabbit testis are essential for development of the male phenotype. Sexually dimorphic hormones play a key role in the transition from an undifferentiated gonad into the mature testis and ovary. Marsupials, with their altricial young, provide an accessible model for the study of sexual differentiation because most of these events occur postnatally, while the young are attached to teats within their mothers' pouches. The relatively long time-course for the marsupial sexual differentiation has provided an excellent opportunity to correlate morphological changes with the genes and hormones that control them. Using this model species we have demonstrated that not all sexual dimorphisms are controlled by hormones. Virilization of the prostate and phallus is androgen dependent but appears to rely on circulating 5alpha-androstane-3alpha, 17beta-diol which is converted to dihydrotestosterone in these target tissues. Collectively these studies have led to the development of new paradigms to explain the hormonal mechanisms mediating sexual differentiation.

Animals↗

Influence of ovariectomy on metabolic and endocrine parameters during sexual development in the female pig.

During pubertal maturation, the increase in blood concentrations of sexual steroids is associated with a spurt in plasma IGF-I in primates, rats and cattle. However, data on the influence of sex steroids on plasma IGF-I during this physiological period are contradictory. Therefore, the present experiment was undertaken to understand better the relationships between pubertal development, energy metabolic regulation and the IGF-I/IGFBP system in crossbred gilts (Large White x Landrace). Circulating concentrations of hormones and metabolites were examined in ovariectomized (n = 6) and sham-operated females (n = 9) during sexual development. Surgery and first blood samplings were performed at 70 days of age. Growth curves were similar in ovariectomized and entire females. First oestrus and ovulation occurred between 178 and 209 days in entire gilts. From 84 days of age, plasma FSH concentration was lower in sham-operated than in ovariectomized gilts (P < 0.01) showing the negative feedback exerted by ovarian secretions on the gonadotrophin axis in entire gilts. Preprandial concentration of plasma glucose was not influenced by age whereas plasma free fatty acids decreased with age (P < 0.01). Concentrations of both metabolites were similar in ovariectomized and entire gilts. Plasma IGF-I and 43-39 kDa IGFBP levels increased whereas plasma 34 kDa IGFBP decreased with age (P < 0.01) and none of the levels differed between ovariectomized and entire gilts (P > 0.1). This experiment shows that gonadal steroids are not involved or play only a minor role in the control of IGF-I and IGFBP plasma levels during pubertal development in the female pig.

Analysis of Variance↗