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The csnD/csnE signalosome genes are involved in the Aspergillus nidulans DNA damage response.

The signalosome (CSN) is a conserved multiprotein complex involved in regulation of eukaryotic development and is also required to activate ribonucleotide reductase for DNA synthesis. In Aspergillus nidulans, csnD/csnE are key regulators of sexual development. Here, we investigated whether the csnD/csnE genes are involved in the DNA damage response in this fungus. The growth of the csnD/csnE deletion mutants was reduced by subinhibitory concentrations of hydroxyurea, camptothecin, 4-nitroquinoline oxide, and methyl methanesulfonate. A. nidulans increases csnD/csnE mRNA levels when it is challenged by different DNA-damaging agents. There is no significant transcriptional induction of the csnE promoter fused with lacZ gene in the presence of DNA-damaging agents, suggesting that increased mRNA accumulation is due to increased mRNA stability. Septation was not inhibited in the csnD/csnE deletion mutants while DeltauvsB DeltacsnE presented an increase in septation upon DNA damage caused by methyl methanesulfonate, suggesting that uvsB(ATR) and csnE genetically interact during checkpoint-dependent inhibition of septum formation. The double DeltacsnD/DeltacsnE DeltanpkA mutants were more sensitive to DNA-damaging agents than were the respective single mutants. Our results suggest that csnD/csnE genes are involved in the DNA damage response and that NpkA and UvsB(ATR) genetically interact with the signalosome.

Aspergillus nidulans↗

Perceptions of men's sexual health behaviour.

AIM: The aim of the pilot study was to explore lay and professional perceptions of men's sexual health behaviour and the factors affecting risk in relation to sexually transmitted infection (STI). METHOD: The research was conducted in two cities in the UK and data were collected using a semi-structured questionnaire. A purposive sampling technique was used to ensure that a mixture of lay and professional responses was received. RESULTS: The results indicate that lay and professional respondents perceive that STI risk is related to social inequality. Men from minority ethnic groups and lower social classes are believed to be at particular risk of contracting STIs but their needs are not being adequately addressed by sexual health services and information providers. CONCLUSION: Further research is needed to discover the ways in which sexual health and risk are affected by social inequality. Service providers and planners need to consider the possible consequences of developing sexual health services for the male population.

Adult↗

Effect of improved nutrition during calfhood on serum metabolic hormones, gonadotropins, and testosterone concentrations, and on testicular development in bulls.

The objective of the present study was to evaluate the effects of improved nutrition during calfhood on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls. Bulls received high (n=17) or control nutrition (n=16) diets from 10 to 30 week of age and the same control nutrition diet from 31 to 74 week of age. Improved nutrition during calfhood resulted in a more sustained period of elevated LH secretion (pulse frequency and total secretion in 10h) during the early gonadotropin rise. GnRH-stimulated LH secretion was not affected by diet, indicating that pituitary responsiveness was not altered; therefore, improved nutrition had direct effects on GnRH secretion by the hypothalamus. Insulin and insulin-like growth factor-I (IGF-I) concentrations were greater during calfhood in bulls receiving high nutrition, indicating that these metabolic hormones might be involved in regulating GnRH and LH secretion. Improved nutrition also resulted in increased testosterone secretion that was associated with greater circulating IGF-I concentrations, suggesting a role for this metabolic hormone in regulating Leydig cell number and function. Furthermore, improved nutrition during calfhood resulted in greater testicular weight and sperm production in mature bulls, indicating that increased LH secretion during calfhood, and increased IGF-I and testosterone concentrations during calfhood and peripubertal period were associated with greater testicular cell proliferation and enhanced function.

Aging↗

The McCune-Albright syndrome.

The presence of polyostotic fibrous dysplasia of bone, hyperpigmented skin macules, and precocious sexual development in children is known as the McCune-Albright syndrome. To date, a complex combination of multiple endocrinopathies including goiter, hyperthyroidism, acromegaly, Cushing syndrome, hyperprolactinemia, sexual precocity, hyperparathyroidism, and hypophosphatemic hyperphosphaturic rickets have been described in association with this syndrome. Even though the pathogenetic mechanisms involved in the development of the endocrinopathies is unknown, it was assumed for many years that hypothalamic dysfunction was the cause in most cases. The overwhelming amount of data now permits the development of an alternate hypothesis; one of hyperfunctioning endocrine organs working with relative autonomy from hypothalamic control.

Adrenalectomy↗

Expression of steroidogenic factor-1 in frog embryo and developing gonad.

Steroidogenic factor-1 (SF-1), originally identified as an orphan nuclear receptor that regulates expression of genes encoding cytochrome P-450 steroid hydroxylases, is an essential transcriptional factor for adrenal and gonadal development in mammals. Since sex steroid hormones have been shown to play important roles in the sex determination of frogs, it is of interest to know how SF-1 gene expression is regulated during the sexual development of this organism. A previous study isolated the cDNA of the frog Rana rugosa SF-1 (rrSF-1) and found sexual differences in its gene expression in adult frogs; positive in testis and negative in ovary (Kawano et al., 1998). This study examined rrSF-1 gene expression in frog embryos and developing and mature gonads by immunohistochemical staining using anti-rrSF-1 protein antibody for protein localization and by in situ hybridization analysis for mRNA transcription. The results obtained in this study indicated that cells expressing SF-1 that originate in the mesoderm and endoderm probably migrate into the developing gonad via the dorsal mesentery, genital ridge, and mesorchium or mesovarium. Thus, SF-1 may play an important role in gonadal development in amphibians.

Adrenal Glands↗

Gene expression changes induced in mouse liver by di(2-ethylhexyl) phthalate.

Increasing chemical use necessitates a better understanding of how pollutants, such as di(2-ethylhexyl) phthalate (DEHP), a peroxisome proliferator and a phthalate plasticizer, affect human health. To understand the effects of DEHP exposure, we utilized microarray technology to identify novel DEHP targets in livers of male C57BL/6 mice treated with 1.0% dietary DEHP for 13 weeks. We identified 51 DEHP-regulated genes; these genes are involved in, but not limited to, peroxisome proliferation, xenobiotic detoxification, oxidative stress response, immune function, steroid hormone metabolism, testis development, and pheromone transport. The reproductive toxicity mechanism of DEHP may be due to its effects on steroid hormone metabolism and sexual development. Confirmation of microarray results with Northern blots demonstrated that both low- and high-dose DEHP treatments altered the expression of genes associated with testis development and steroid hormone synthesis. Vanin-1, a regulator of testis development, was upregulated after exposure to 0.2 and 1.0% DEHP by 1.8- and 2.9-fold, respectively. Several genes involved in hormone metabolism were also regulated by DEHP. 11betaHSDI was downregulated 1.8- and 3.1-fold by 0.2 and 1.0% DEHP, respectively, while HSD3b5 was suppressed similarly by 0.2% DEHP, 1.5-fold, and more severely by 1.0% DEHP, 8.0-fold. Interestingly, food restriction had a similar effect to DEHP on several genes, including HSD3b5. In addition, steroidogenic gene cyp7B1 was downregulated while phospholipid transfer protein and cyp2B9 were induced. Genes peripherally associated with steroid hormones were also affected: ALDH3, GSTtheta2, and Id2. Collectively, our data validate the concern for DEHP as a reproductive developmental toxicant.

11-beta-Hydroxysteroid Dehydrogenases↗

[Genetic support for gonadal development].

The problem of the sexes appearance has concerned the mankind since the oldest times. The paper surveys the theories that appeared during the ages, from Plato to the beginning of the 20th century when the spermatozoon was differentiated from the ovule, the chromosomes were identified and their importance for determining the sex was recognized. The paper reports on the role of the HY antigen--discovered in 1955 by Eichwald and Simser--and its mode of action, corroborating the control structural gene. The differentiating disturbances of the gonads are reviewed: the disturbances in the development of the male sex, its hormonal and enzymatic bases The authors also discuss the theories trying to explain the genetic mutations that have a diminishing effect on the estrogenic synthesis or on the appearance of the resistance to estrogens, emphasizing that the estrogenic effect is essential for the embryo life. The sexual development is too complex to be due only to the sex chromosomes. Its most important stages are determined by the genes located both on the autosomal chromosomes and on the sexual ones.

Disorders of Sex Development↗

Distribution of sex steroid hormone receptors in the avian brain: functional implications for neural sex differences and sexual behaviors.

Developmental and seasonal changes in the production of androgens, estrogens, and progestins seem to control sex-specific differentiation and seasonal changes in appetitive and consummatory sexual behaviors of birds. This results in profound sex differences in the quality (sex-specific) or quantity (sex-typical) of behaviors such as courtship, territoriality, or copulation. Steroids affect the brain by binding to intracellularly located receptors. The same brain areas express androgen, estrogen, and progesterone receptors in male and female brains. Sex differences in these genetically determined patterns occur in the size of neuron populations that intrinsically express sex steroid receptors. Further permanent sex differences are subsequent to degenerative fates of receptor expressing neuron populations during ontogeny. Transient sex differences in receptor expression appear to be due to area-specific up- and down-regulation of receptor levels, reflecting transient changes in the level of circulating steroids, changes in environmental conditions, or in the physiological status of the individuals. In particular, intrinsic sex differences in the expression pattern of sex steroid receptors and steroid-independent regulation of the expression level of these receptors in the brain are limiting mechanisms for gonad-dependent sexual development and activities.

Animals↗

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans↗

Targeting transforming growth factor alpha expression to discrete loci of the neuroendocrine brain induces female sexual precocity.

Precocious puberty of cerebral origin is a poorly understood disorder of human sexual development, brought about by the premature activation of those neurons that produce luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual maturation. An increased production of transforming growth factor alpha (TGF alpha) in the hypothalamus has been implicated in the mechanism underlying both normal and precocious puberty. We have now used two gene delivery systems to target TGF alpha overexpression near LHRH neurons in immature female rats. Fibroblasts infected with a retroviral construct in which expression of the human TGF alpha gene is constitutively driven by the phosphoglycerate kinase promoter, or transfected with a plasmid in which TGF alpha expression is controlled by an inducible metallothionein promoter, were transplanted into several regions of the hypothalamus. When the cells were in contact with LHRH nerve terminals or in the vicinity of LHRH perikarya, sexual maturation was accelerated. These results suggest that precocious puberty of cerebral origin may result from a focal disorder of TGF alpha production within the confines of the LHRH neuron microenvironment.

3T3 Cells↗

Embryo and endosperm development is disrupted in the female gametophytic capulet mutants of Arabidopsis.

The female gametophyte of higher plants gives rise, by double fertilization, to the diploid embryo and triploid endosperm, which develop in concert to produce the mature seed. What roles gametophytic maternal factors play in this process is not clear. The female-gametophytic effects on embryo and endosperm development in the Arabidopsis mea, fis, and fie mutants appear to be due to gametic imprinting that can be suppressed by METHYL TRANSFERASE1 antisense (MET1 a/s) transgene expression or by mutation of the DECREASE IN DNA METHYLATION1 (DDM1) gene. Here we describe two novel gametophytic maternal-effect mutants, capulet1 (cap1) and capulet2 (cap2). In the cap1 mutant, both embryo and endosperm development are arrested at early stages. In the cap2 mutant, endosperm development is blocked at very early stages, whereas embryos can develop to the early heart stage. The cap mutant phenotypes were not rescued by wild-type pollen nor by pollen from tetraploid plants. Furthermore, removal of silencing barriers from the paternal genome by MET1 a/s transgene expression or by the ddm1 mutation also failed to restore seed development in the cap mutants. Neither cap1 nor cap2 displayed autonomous seed development, in contrast to mea, fis, and fie mutants. In addition, cap2 was epistatic to fis1 in both autonomous endosperm and sexual development. Finally, both cap1 and cap2 mutant endosperms, like wild-type endosperms, expressed the paternally inactive endosperm-specific FIS2 promoter GUS fusion transgene only when the transgene was introduced via the embryo sac, indicating that imprinting was not affected. Our results suggest that the CAP genes represent novel maternal functions supplied by the female gametophyte that are required for embryo and endosperm development.

Arabidopsis↗

[Animal experiment studies on the neurohumoral control of female puberty. 2. Studies on the influence of amygdala and of the hippocampus on sex maturation].

Immature female rats were bilaterally lesioned in the rostral or caudal part of the mediocortical amygdala (MCA) or in the ventral hippocampus (VHPC) at 21 days of age. In a second experiment, simultaneous lesioning of the MCA or VHPC and the medial preoptic area or hypothalamic ventromedial-arcuate region was performed in 21-day-old rats. Finally, discrete lesions were placed into the anterior or posterior parts of the medial (MAN) or cortical amygdaloid nuclei ath 21, 26 or 32 days of age. The effects of the different treatments on the onset of puberty were evaluated by recording the age at vaginal opening and first ovulation, the body weight on the day of vaginal opening, and the subsequent ovarian or vaginal cyclicity. The following conclusions may be drawn from the findings obtained: 1. At three weeks of age, the MCA exerts a gonadotropininhibiting function that is localized in the anterior part of the MAN. This activity is not demonstrable in older females. 2. The MAN, particularly its posterior part, may play an important role in the prepuberal maturation of the maturation of the neurohormonal ovulatory mechanisms that takes place in female rats during the fourth week of life. 3. The VHPC may be involved in the control of female sexual development mainly by its growth-stimulating activity. The results suggest an essential role of the subcortical limbic system in female sexual maturation and offer an explanation of contradictory findings on the gonadotrophin-controlling function of the MCA before puberty.

Amygdala↗

Neonatal and pubertal development in males of a cooperatively breeding primate, the cotton-top tamarin (Saguinus oedipus oedipus).

In cooperatively breeding groups of mammals, reproduction is usually restricted to a small number of individuals within the social group. Sexual development of mammals can be affected by social environment, but we know little regarding effects of the cooperative-breeding system on males. Cotton-top tamarin (Saguinus oedipus oedipus) offspring typically do not reproduce in their natal group, even though they may be physically mature. We examined neonatal and pubertal development in captive male cotton-top tamarins as an example of reproductive development within a cooperative-breeding system and to compare cotton-top tamarins with the general primate model. Puberty was characterized using both hormonal and physical measures. Data were collected on urinary levels of LH, testosterone (T), dihydrotestosterone (DHT), cortisol, and the ratio of DHT to T; testicular development; body weight; and breeding age. We determined that 1) pubertal LH secretion began at Week 37, 2) a surge of T secretion followed at Weeks 41-44, and 3) an increase in the metabolism of T to DHT may have occurred at an average age of 48.6 wk. Most of the rapid weight gain was completed by Week 24, before hormonal increases and rapid scrotal growth. We concluded that rapid pubertal testicular growth in captive cotton-top males was completed by an average 76 wk, but that completion of the individual pubertal spurt can occur between 56 and 122 wk. In a cooperative-breeding system, the opportunity for successful reproduction is dictated by the social environment, but we found no evidence that male offspring were developmentally suppressed in their natal social groups. Our findings suggest that puberty in male New World callitrichid primates occurs more quickly than puberty in Old World primates, even though both have similar patterns of development.

Aging↗

Site-directed mutagenesis of the magB gene affects growth and development in Magnaporthe grisea.

G protein signaling is commonly involved in regulating growth and differentiation of eukaryotic cells. We previously identified MAGB, encoding a Galpha subunit, from Magnaporthe grisea, and disruption of MAGB led to defects in a number of cellular responses, including appressorium formation, conidiation, sexual development, mycelial growth, and surface sensing. In this study, site-directed mutagenesis was used to further dissect the pleiotropic effects controlled by MAGB. Conversion of glycine 42 to arginine was predicted to abolish GTPase activity, which in turn would constitutively activate G protein signaling in magB(G42R). This dominant mutation caused autolysis of aged colonies, misscheduled melanization, reduction in both sexual and asexual reproduction, and reduced virulence. Furthermore, magB(G42R) mutants were able to produce appressoria on both hydrophobic and hydrophilic surfaces, although development on the hydrophilic surface was delayed. A second dominant mutation, magB(G203R) (glycine 203 converted to arginine), was expected to block dissociation of the Gbetagamma from the Galpha subunit, thus producing a constitutively inactive G protein complex. This mutation did not cause drastic phenotypic changes in the wild-type genetic background, other than increased sensitivity to repression of conidiation by osmotic stress. However, magB(G203R) is able to complement phenotypic defects in magB mutants. Comparative analyses of the phenotypical effects of different magB mutations are consistent with the involvement of the Gbetagamma subunit in the signaling pathways regulating cellular development in M. grisea.

Amino Acid Sequence↗

The mating-type locus B alpha 1 of Schizophyllum commune contains a pheromone receptor gene and putative pheromone genes.

Analysis of the multispecific B alpha mating-type locus of Schizophyllum commune provided evidence that pheromones and pheromone receptors govern recognition of self versus non-self and sexual development in this homobasidiomycetous fungus. Four subclones of an 8.2 kb genomic fragment carrying B alpha 1 specificity induced B-regulated sexual morphogenesis when introduced into a strain with one of the eight compatible B alpha specificities that are known to exist in nature. One of these clones, which activated all other B alpha specificities, contains a gene termed bar1. The predicted protein product of bar1, as well as that of bar2, a homologous gene isolated from a B alpha 2 strain, has significant homology to known fungal pheromone receptor proteins in the rhodopsin-like superfamily of G protein-linked receptors. The other three active B alpha 1 clones were subcloned further to identify the minimal active element in each clone. Every active subclone contains a putative pheromone gene ending in a signal for possible isoprenylation. A message of approximately 600 bp was observed for one of these genes, bap1(1). This paper presents the first evidence for a system of multiple pheromones and pheromone receptors as a basis for multispecific mating types in a fungus.

Amino Acid Sequence↗

The morphogenesis of human sphincter urethrae muscle.

The morphogenesis of the sphincter urethrae muscle was studied in human ontogeny. Muscles of 65 embryos and fetuses, 7 newborns, 3 children and 3 adults of both sexes were examined histologically and by means of microdissection. Three developmental stages can be recognized in terms of morphogenetic events, histogenesis and development of sexual dimorphism. In the sexually indifferent stage (up to approximately 50 mm crown-rump length), the sphincter urethrae primordium is formed by a shallow arch apposed only to the ventrolateral wall of the urethra. The primordium extends from the level of the urogenital diaphragm up to the vesicourethral transition. It consists of a condensation of mononuclear cells. Myotubes appear in fetuses of 30 mm crown-rump length. During the second stage (until birth) sexual dimorphism develops in conjunction to the formation of the prostate and vagina. In this stage, the sphincter urethrae muscle fibres gradually extend to the posterior wall of the urethra. At the same time cranially situated muscle fibres project to the lateral wall of the prostate, whereas in females caudally located muscle fibres attach to the lateral wall of the vagina. In this way the sphincter achieves the sexually distinct form. The definitive arrangement develops in the third morphogenic stage (after birth), in which a complete muscle ring is formed by encircling the urethra in the infraprostatic part in males and in the upper, larger part of the sphincter in females. The sphincter urethrae muscle is located inside the sling of the puborectalis muscle in both sexes, but no muscle fibres connect them to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Recent studies on the reproductive biology of the schistosomes and their relevance to speciation in the Digenea.

The members of the family Schistosomatidae, dioecious Digenea, are discussed with regard to their distribution, intermediate and definitive host-parasite relationships. The biological species concept is considered together with the difficulties of its application to Schistosoma spp. and the Digenea. The correlation between pairing of adult schistosomes, physical and sexual development and the maintenance of reproductive potential is emphasised. Development of the female reproductive system does not depend upon species-specific pairing. In some combinations, e.g., Schistosoma haematobium/Schistosoma intercalatum and Schistosoma bovis/Schistosoma curassoni, a specific mate choice system apparently does not exist, whereas it does in other combinations, e.g., Schistosoma mansoni/Schistosoma intercalatum. In mixed infections change of mate may occur and when the opportunity arises heterospecific pairs of worms will change partners to conspecific pairs. Interspecific pairing in adult schistosomes will lead to either hybridisation or parthenogenesis. Yet the majority of schistosomes that inhabit the same definitive host maintain their genetic identity: specific mate recognition, site selection within the host and heterologous immunity have been suggested as isolating mechanisms. Experimental intraspecific crosses have enabled evaluation of the degree to which some populations separated and became reproductively isolated through pre-mating isolating mechanisms, indicative of incipient speciation, e.g., the Lower Guinea and Zaire strains of S. intercalatum. The occurrence and significance of parthenogenesis in schistosomes and other species of Digenea are discussed. The consequences of interspecific mating interactions in schistosomes with regard to parasite epidemiology, interspecific competition and genetic heterogeneity are debated. Geographical isolation and host specificity represent important pre-zygotic isolating mechanisms. It is suggested that site selection within the host and heterologous immunity may both reduce interspecific genetic interchange when digenean parasites utilise the same definitive host.

Animals↗

Allied health professional students' perceived level of comfort in clinical situations that have sexual connotations.

This study examined the anticipated level of comfort of 1,132 higher education students enrolled across physical therapy, occupational therapy, medical radiation sciences, rehabilitation counseling, leisure and health sciences, and behavioral health science professional courses. Participants were asked to indicate their anticipated level of comfort for a range of clinical interactions that have sexual implications. More than half of the students anticipated that they would not feel comfortable in dealing with the issues raised in 9 of the 19 sexually themed items. Significant gender differences were identified for some of these items. These gender differences should be taken into account when developing sexuality curricula. Feelings of discomfort when interacting with clients could impede appropriate therapeutic interventions. Further research investigating the nature and cause of discomfort in clinical settings is required. Studies that examine the usefulness of sexuality education programs in increasing practitioner comfort also should be carried out.

Adolescent↗