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OBJECTIVE: Secrecy about a childs difference of sex development (DSD) can lead to internalized shame and stigma. We explored how teenagers and adults with DSD, parents, healthcare providers, and allied professionals value and perceive patient education. METHODS: Stakeholders (n = 110) completed qualitative semi-structured interviews. Relevant themes for educational content were queried and organized. RESULTS: Education was consistently identified as essential to successful outcomes. There was less consistency in how to educate patients. Disagreement existed regarding who should champion the education process. Participants believed medically relevant information should be shared gradually with attention to developmental capacity. Details were lacking regarding how much or what information to share. Participants noted that vetted resources were helpful. Benefits of sharing condition-specific information with patients included supporting their psychosocial development. Barriers included parental resistance to sharing information due to shame/stigma, and cultural and/or family dynamics. CONCLUSIONS: Stakeholders different perspectives regarding patient DSD education warrant future research to focus on the design, evaluation, and implementation of education-focused interventions. PRACTICE IMPLICATIONS: Healthcare providers are responsible for supporting the education of children and teenagers with DSD about their condition. When considering barriers, adopting a cultural or family systems framework can reduce parental resistance and promote open dialogue.

All children have a sexuality within themselves which they express in different ways, some children explore their sexuality more than others. Natural sexual exploration is normal but in case of deviating or abnormal sexual behavior it needs to be addressed. The aim of this study is to find out what exactly an abnormal sexual behavior is and how it is defined. This study also covers if pornography has an effect on sexual behavior and what kind of interventions that are available to help this group of children. The method used in this study is a literature search where two databases have been used. These are Psycinfo and Sociological Abstracts. A selection of 21 articles that were peer reviewed and considered relevant to our study was chosen and used to obtain a result. The result of our study addresses how abnormal sexual behavior amongst young boys is harmful not only for the children themselves but also whoever gets exposed to the harmful behavior. Children with abnormal sexual behavior can explore their sexuality on anyone. It can be with strangers or children younger than themselves and at the same time using coercion and violence. Children with abnormal sexual behavior have a sexual behavior similar to adults. The result has also shown that there can be various different reasons to why an abnormal sexual behavior occurs. It can be the cause of trauma, former sexual abuse, a disfunctional family or a lack of social skills. Pornography also has a big impact on the behavior and can cause a lot of negative consequences for children. There is a large variation of interventions that are offered to children with these kinds of problems.There is everything from individual therapy, CBT treatment to support and help for the family as a whole. The most important thing is to help the child as fast as possible to prevent recidivism.

All children have a sexuality within themselves which they express in different ways, some children explore their sexuality more than others. Natural sexual exploration is normal but in case of deviating or abnormal sexual behavior it needs to be addressed. The aim of this study is to find out what exactly an abnormal sexual behavior is and how it is defined. This study also covers if pornography has an effect on sexual behavior and what kind of interventions that are available to help this group of children. The method used in this study is a literature search where two databases have been used. These are Psycinfo and Sociological Abstracts. A selection of 21 articles that were peer reviewed and considered relevant to our study was chosen and used to obtain a result. The result of our study addresses how abnormal sexual behavior amongst young boys is harmful not only for the children themselves but also whoever gets exposed to the harmful behavior. Children with abnormal sexual behavior can explore their sexuality on anyone. It can be with strangers or children younger than themselves and at the same time using coercion and violence. Children with abnormal sexual behavior have a sexual behavior similar to adults. The result has also shown that there can be various different reasons to why an abnormal sexual behavior occurs. It can be the cause of trauma, former sexual abuse, a disfunctional family or a lack of social skills. Pornography also has a big impact on the behavior and can cause a lot of negative consequences for children. There is a large variation of interventions that are offered to children with these kinds of problems.There is everything from individual therapy, CBT treatment to support and help for the family as a whole. The most important thing is to help the child as fast as possible to prevent recidivism.

Wildfires drastically impact the soil environment, altering the soil organic matter, forming pyrolyzed compounds, and markedly reducing the diversity of microorganisms. Pyrophilous fungi, especially the species from the orders Pezizales and Agaricales, are fire-responsive fungal colonizers of post-fire soil that have historically been found fruiting on burned soil and thus may encode mechanisms of processing these compounds in their genomes. Pyrophilous fungi are diverse. In this work, we explored this diversity and sequenced six new genomes of pyrophilous Pezizales fungi isolated after the 2013 Rim Fire near Yosemite Park in California, USA: Pyronema domesticum, Pyronema omphalodes, Tricharina praecox, Geopyxis carbonaria, Morchella snyderi, and Peziza echinospora. A comparative genomics analysis revealed the enrichment of gene families involved in responses to stress and the degradation of pyrolyzed organic matter. In addition, we found that both protein sequence lengths and G + C content in the third base of codons (GC3) in pyrophilous fungi fall between those in mesophilic/nonpyrophilous and thermophilic fungi. A comparative transcriptome analysis of P. domesticum under two conditions - growing on charcoal, and during sexual development - identified modules of genes that are co-expressed in the charcoal and light-induced sexual development conditions. In addition, environmental sensors such as transcription factors STE12, LreA, LreB, VosA, and EsdC were upregulated in the charcoal condition. Taken together, these results highlight genomic adaptations of pyrophilous fungi and indicate a potential connection between charcoal tolerance and fruiting body formation in P. domesticum.

•Wildfires drastically impact the soil environment, altering the soil organic matter, forming pyrolyzed compounds, and markedly reducing the diversity of microorganisms. •Pyrophilous fungi, especially the species from the orders Pezizales and Agaricales, are fire-responsive fungal colonizers of post-fire soil that have historically been found fruiting on burned soil and thus may encode mechanisms of processing these compounds in their genomes. Pyrophilous fungi are diverse. In this work, we explored this diversity and sequenced six new genomes of pyrophilous Pezizales fungi isolated after the 2013 Rim Fire near Yosemite Park in California, USA: Pyronema domesticum, Pyronema omphalodes, Tricharina praecox, Geopyxis carbonaria, Morchella snyderi, and Peziza echinospora. •A comparative genomics analysis revealed the enrichment of gene families involved in responses to stress and the degradation of pyrolyzed organic matter. In addition, we found that both protein sequence lengths and G + C content in the third base of codons (GC3) in pyrophilous fungi fall between those in mesophilic/nonpyrophilous and thermophilic fungi. •A comparative transcriptome analysis of P. domesticum under two conditions - growing on charcoal, and during sexual development - identified modules of genes that are co-expressed in the charcoal and light-induced sexual development conditions. In addition, environmental sensors such as transcription factors STE12, LreA, LreB, VosA, and EsdC were upregulated in the charcoal condition. •Taken together, these results highlight genomic adaptations of pyrophilous fungi and indicate a potential connection between charcoal tolerance and fruiting body formation in P. domesticum.

BACKGROUND: Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones. METHODS AND RESULTS: We used data from the Danish nationwide Puberty Cohort. Information on CHD was obtained from the Danish National Patient Register. Information on pubertal development was obtained from 15 780 children through questionnaires answered half-yearly from 11 years until 18 years or full maturity. Using a multivariable regression model for censored time-to-event data, mean difference in age at attaining each pubertal milestone was estimated, including a combined pubertal marker. Compared with children without CHD, analyses were performed for both CHD overall and subdivided into simple and complex CHD. In a subanalysis, analyses were repeated in children born at term. In total, 137 children (62 boys and 75 girls) had a CHD diagnosis. Overall, no difference in age at pubertal timing was observed for children with CHD compared with unaffected children. The average differences were small for both boys (1.6 [95% CI, −2.6 to 5.7] months) and girls (1.0 [95% CI, −2.5 to 4.4] months). The same differences were observed when subdividing into simple or complex CHD and when restricting to children born at term. CONCLUSIONS: We found no association between CHD and pubertal timing. For the group of children with complex CHD, we were unable to exclude a later pubertal timing.

The cap-binding protein eIF4E, through its interaction with eIF4G, constitutes the core of the eIF4F complex, which plays a key role in the circularization of mRNAs and their subsequent cap-dependent translation. In addition to its fundamental role in mRNA translation initiation, other functions have been described or suggested for eIF4E, including acting as a proviral factor and participating in sexual development. We used CRISPR/Cas9 genome editing to generate melon eif4e knockout mutant lines. Editing worked efficiently in melon, as we obtained transformed plants with a single-nucleotide deletion in homozygosis in the first eIF4E exon already in a T0 generation. Edited and non-transgenic plants of a segregating F2 generation were inoculated with Moroccan watermelon mosaic virus (MWMV); homozygous mutant plants showed virus resistance, while heterozygous and non-mutant plants were infected, in agreement with our previous results with plants silenced in eIF4E. Interestingly, all homozygous edited plants of the T0 and F2 generations showed a male sterility phenotype, while crossing with wild-type plants restored fertility, displaying a perfect correlation between the segregation of the male sterility phenotype and the segregation of the eif4e mutation. Morphological comparative analysis of melon male flowers along consecutive developmental stages showed postmeiotic abnormal development for both microsporocytes and tapetum, with clear differences in the timing of tapetum degradation in the mutant versus wild-type. An RNA-Seq analysis identified critical genes in pollen development that were down-regulated in flowers of eif4e/eif4e plants, and suggested that eIF4E-specific mRNA translation initiation is a limiting factor for male gametes formation in melon

BACKGROUND: Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones. METHODS AND RESULTS: We used data from the Danish nationwide Puberty Cohort. Information on CHD was obtained from the Danish National Patient Register. Information on pubertal development was obtained from 15 780 children through questionnaires answered half-yearly from 11 years until 18 years or full maturity. Using a multivariable regression model for censored time-to-event data, mean difference in age at attaining each pubertal milestone was estimated, including a combined pubertal marker. Compared with children without CHD, analyses were performed for both CHD overall and subdivided into simple and complex CHD. In a subanalysis, analyses were repeated in children born at term. In total, 137 children (62 boys and 75 girls) had a CHD diagnosis. Overall, no difference in age at pubertal timing was observed for children with CHD compared with unaffected children. The average differences were small for both boys (1.6 [95% CI, −2.6 to 5.7] months) and girls (1.0 [95% CI, −2.5 to 4.4] months). The same differences were observed when subdividing into simple or complex CHD and when restricting to children born at term. CONCLUSIONS: We found no association between CHD and pubertal timing. For the group of children with complex CHD, we were unable to exclude a later pubertal timing.

Nonrecombining sex chromosomes, like the mammalian Y, often lose genes and accumulate transposable elements, a process termed degeneration. The correlation between suppressed recombination and degeneration is clear in animal XY systems, but the absence of recombination is confounded with other asymmetries between the X and Y. In contrast, UV sex chromosomes, like those found in bryophytes, experience symmetrical population genetic conditions. Here, we generate nearly gapless female and male chromosome-scale reference genomes of the moss Ceratodon purpureus to test for degeneration in the bryophyte UV sex chromosomes. We show that the moss sex chromosomes evolved over 300 million years ago and expanded via two chromosomal fusions. Although the sex chromosomes exhibit weaker purifying selection than autosomes, we find that suppressed recombination alone is insufficient to drive degeneration. Instead, the U and V sex chromosomes harbor thousands of broadly expressed genes, including numerous key regulators of sexual development across land plants.

The importance of children being treated in a way that conveys the message that their sexuality is something positive and enjoyable has been emphasized by the WHO. The aim of the study was therefore to investigate how experienced preschool teachers experience and respond to children's sexuality. Focus group discussions were used as a method of gathering teachers' knowledge and experience. The results showed that the interviewed preschool teachers agreed that children's sexuality is something natural and important to consider. According to the informants, further training within the subject was also unusual and discussions with colleagues and parents were usually conducted only in the event of incidents. The importance of confirming and responding to children's sexuality in a positive way was analyzed and it was discussed whether children's sexuality is distracted too often and if the focus on negative sexuality prevails. One conclusion was that children's sexuality should be normalized so that adults' fears do not harm children's sexual development., Vikten av att barn bemöts på ett sätt som förmedlar budskapet om att deras sexualitet är något positivt och njutningsfullt har framhållits av WHO. Syftet med studien var därför att undersöka hur erfarna förskollärare upplever och bemöter barns sexualitet. Som metod användes fokusgruppsdiskussioner för att ta del av förskollärares kunskap och erfarenhet. I resultatet framkom det att de intervjuade förskollärarna var eniga om att barns sexualitet är något naturligt och viktigt att beakta. Enligt informanterna var fortbildning inom ämnet dock ovanligt och diskussioner med kollegor och föräldrar fördes vanligen endast vid incidenter. Vikten av att barns sexualitet bekräftas och bemöts på ett positivt sätt analyserades och det diskuterades huruvida barns sexualitet avleds för ofta och utifall fokus på negativ sexualitet tagit överhanden. En slutsats var att barns sexualitet borde normaliseras så att inte vuxnas rädslor skadar barns sexuella utveckling.

Most animal species consist of two distinct sexes. At the morphological, physiological, and behavioral levels the differences between males and females are numerous and dramatic, yet at the genomic level they are often slight or absent. This disconnect is overcome because simple genetic differences or environmental signals are able to direct the sex-specific expression of a shared genome. A canonical picture of how this process works in insects emerged from decades of work on Drosophila. But recent years have seen an explosion of molecular-genetic and developmental work on a broad range of insects. Drawing these studies together, we describe the evolution of sexual dimorphism from a comparative perspective and argue that insect sex determination and differentiation systems are composites of rapidly evolving and highly conserved elements.

Despite being collectively among the most frequent congenital developmental conditions worldwide, differences of sex development (DSD) lack recognition and research funding. As a result, what constitutes optimal management remains uncertain. Identification of the individual conditions under the DSD umbrella is challenging and molecular genetic diagnosis is frequently not achieved, which has psychosocial and health-related repercussions for patients and their families. New genomic approaches have the potential to resolve this impasse through better detection of protein-coding variants and ascertainment of under-recognized aetiology, such as mosaic, structural, non-coding or epigenetic variants. Ultimately, it is hoped that better outcomes data, improved understanding of the molecular causes and greater public awareness will bring an end to the stigma often associated with DSD.

The importance of children being treated in a way that conveys the message that their sexuality is something positive and enjoyable has been emphasized by the WHO. The aim of the study was therefore to investigate how experienced preschool teachers experience and respond to children's sexuality. Focus group discussions were used as a method of gathering teachers' knowledge and experience. The results showed that the interviewed preschool teachers agreed that children's sexuality is something natural and important to consider. According to the informants, further training within the subject was also unusual and discussions with colleagues and parents were usually conducted only in the event of incidents. The importance of confirming and responding to children's sexuality in a positive way was analyzed and it was discussed whether children's sexuality is distracted too often and if the focus on negative sexuality prevails. One conclusion was that children's sexuality should be normalized so that adults' fears do not harm children's sexual development., Vikten av att barn bemöts på ett sätt som förmedlar budskapet om att deras sexualitet är något positivt och njutningsfullt har framhållits av WHO. Syftet med studien var därför att undersöka hur erfarna förskollärare upplever och bemöter barns sexualitet. Som metod användes fokusgruppsdiskussioner för att ta del av förskollärares kunskap och erfarenhet. I resultatet framkom det att de intervjuade förskollärarna var eniga om att barns sexualitet är något naturligt och viktigt att beakta. Enligt informanterna var fortbildning inom ämnet dock ovanligt och diskussioner med kollegor och föräldrar fördes vanligen endast vid incidenter. Vikten av att barns sexualitet bekräftas och bemöts på ett positivt sätt analyserades och det diskuterades huruvida barns sexualitet avleds för ofta och utifall fokus på negativ sexualitet tagit överhanden. En slutsats var att barns sexualitet borde normaliseras så att inte vuxnas rädslor skadar barns sexuella utveckling.

In order to ascertain and evaluate mothers' perceptions of the sexual development and behavior of their children with autism, we conducted a questionnaire survey on participants in meetings held in Nagasaki. From among 172 persons who consented to participate in the survey and responded to the self-administered questionnaire, we selected 71 mothers of sons with autism (aged 6 years or over) as the study subjects. The questionnaire included items on children's sexual behaviors, the appearance of secondary sexual characters/sexual development, the mothers' perceptions of the children's sexual development and behavior, and assessments of their own child and persons with autism in general with respect to masturbation, romantic relationships, and marriage. According to the severity of the children's autism, subjects were classified into severe and non-severe groups and the above-mentioned items were compared between the two groups. No significant difference was observed between the two groups in terms of the age at first appearance of secondary sex characters; however, the age at which interest in the opposite sex was first shown was significantly earlier in the non-severe group (p = 0.031). Among 58 children aged 120 months or over, 29 (50.0%) were masturbating and the proportion of such children was significantly larger in the severe group (p = 0.014). Regarding problem sexual behavior, no significant difference was observed in the frequency of worried mothers between the two groups (p = 0.80), while "talking about sex in public" was more frequent in the non-severe group (p = 0.018). Approximately 80% of the mothers in both groups had positive views about masturbation both for their own child and for persons with autism in general; however, the proportion of mothers showing positive views about romantic relationships or marriage was significantly smaller in the severe group (p<0.0001). The present study demonstrated that mothers' perceptions of sexual development and b, identifier:Acta medica Nagasakiensia. 2008, 53(1), p.1-7

The present study aims to analyze the determining role of biology teachers and guardians in the discursive gap between children's sexuality, sexual curiosity and the sexual depiction of pornography. With an understanding of children's sexuality as holistic and dependent on many perspectives, the study highlights various factors that influence the child's knowledge about Sex and Reproductive Health in the biology subject. The study is an in-depth analysis-of various narratives presented by biology teachers and guardians regarding children’s sexuality and the teaching practice in Sex and Reproductive Health Education in Sweden. The critical discourse analysis is based on critical childhood theory and postconstructivism, which lays the framework for the study’s theoretical underpinnings. This means that an interpretation of respondents' linguistic communication permeates the study.The conclusion is that perceptions of the child's sexuality differ between biology teachers and the guardians, of which different opinions about the teaching content of Sex and Reproductive Health Education can be ascertained. All “important adults” (biology teachers and guardians) agree that pornography depicts a false image of sexual relationships, but when this is to be raised with the pupils, there are split perceptions. Another conclusion is that the determining role and values of teachers and guardians is an aspect that can influence what knowledge middle school pupils are given the opportunity to acquire. This may be significant when considering whether pupils gain sufficient knowledge about sexual relations, in school, in such way that the sexual depiction of pornography is not the only image of sexuality presented to them.

Disorders of sex development (DSD) and reproduction are not uncommon among horses, though knowledge about their molecular causes is sparse. Here we characterized a ~200 kb homozygous deletion in chromosome 29 at 29.7-29.9 Mb. The region contains AKR1C genes which function as ketosteroid reductases in steroid hormone biosynthesis, including androgens and estrogens. Mutations in AKR1C genes are associated with human DSDs. Deletion boundaries, sequence properties and gene content were studied by PCR and whole genome sequencing of select deletion homozygotes and control animals. Deletion analysis by PCR in 940 horses, including 622 with DSDs and reproductive problems and 318 phenotypically normal controls, detected 67 deletion homozygotes of which 79% were developmentally or reproductively abnormal. Altogether, 8-9% of all abnormal horses were homozygous for the deletion, with the highest incidence (9.4%) among cryptorchids. The deletion was found in ~4% of our phenotypically normal cohort, ~1% of global warmblood horses and ponies, and ~7% of draught breeds of general horse population as retrieved from published data. Based on the abnormal phenotype of the carriers, the functionally relevant gene content, and the low incidence in general population, we consider the deletion in chromosome 29 as a risk factor for equine DSDs and reproductive disorders.

The Sox (SRY-related HMG-box) family of transcription factors is involved in the regulation of embryonic development and determination of cell fate. Sox proteins serve as transcriptional regulators that are complexed with other proteins. For this study, we initially cloned and characterized the full-length cDNAs, DNA sequences, and 5′-flanking regions of the common carp Cyprinus carpio Sox30. The sequence analysis suggested that Ccsox30 carried a distinct HMG-box of the Sox family within Cyprinus carpio. Phylogenetic and gene structure analysis revealed that sox30 was homologous to mammalian Sox30, whereas chromosome synteny analysis demonstrated that the position of Cyprinus carpio Sox30 in the genome was different from that of other vertebrates. This might have been due to the split of the Sox30 flanking gene by several genes not yet found near the Ccsox30 in evolution, or because the genome sequencing data was not annotated. The results of Real Tim Quantitative-PCR (RT-qPCR) revealed that Sox30 expression was high in the testes, and the expression was traced in other tissues by researching the tissue distribution of C. carpio and ontogeny of Ccsox30 expression in the gonads. This expression pattern suggested that Ccsox30 may be involved in spermatogonial differentiation and spermatogenesis.

The present study aims to analyze the determining role of biology teachers and guardians in the discursive gap between children's sexuality, sexual curiosity and the sexual depiction of pornography. With an understanding of children's sexuality as holistic and dependent on many perspectives, the study highlights various factors that influence the child's knowledge about Sex and Reproductive Health in the biology subject. The study is an in-depth analysis-of various narratives presented by biology teachers and guardians regarding children’s sexuality and the teaching practice in Sex and Reproductive Health Education in Sweden. The critical discourse analysis is based on critical childhood theory and postconstructivism, which lays the framework for the study’s theoretical underpinnings. This means that an interpretation of respondents' linguistic communication permeates the study.The conclusion is that perceptions of the child's sexuality differ between biology teachers and the guardians, of which different opinions about the teaching content of Sex and Reproductive Health Education can be ascertained. All “important adults” (biology teachers and guardians) agree that pornography depicts a false image of sexual relationships, but when this is to be raised with the pupils, there are split perceptions. Another conclusion is that the determining role and values of teachers and guardians is an aspect that can influence what knowledge middle school pupils are given the opportunity to acquire. This may be significant when considering whether pupils gain sufficient knowledge about sexual relations, in school, in such way that the sexual depiction of pornography is not the only image of sexuality presented to them.

Certain Aspergillus species such as Aspergillus flavus and A. parasiticus are well known for the formation of sclerotia. These developmental structures are thought to act as survival structures during adverse environmental conditions but are also a prerequisite for sexual reproduction. We previously described an A. niger mutant (scl-2) which formed sclerotium-like structures, suggesting a possible first stage of sexual development in this species. Several lines of evidence presented in this study support the previous conclusion that the sclerotium-like structures of scl-2 are indeed sclerotia. These included the observations that: (i) safranin staining of the sclerotia-like structures produced by the scl-2 mutant showed the typical cellular structure of a sclerotium; (ii) metabolite analysis revealed specific production of indoloterpenes, which have previously been connected to sclerotium formation; (iii) formation of the sclerotium-like structures is dependent on a functional NADPH complex, as shown for other fungi forming sclerotia. The mutation in scl-2 responsible for sclerotium formation was identified using parasexual crossing and bulk segregant analysis followed by high throughput sequencing and subsequent complementation analysis. The scl-2 strain contains a mutation that introduces a stop codon in the putative DNA binding domain of a previously uncharacterized Zn(II)2Cys6 type transcription factor (An08g07710). Targeted deletion of this transcription factor (sclB) confirmed its role as a repressor of sclerotial formation and in the promotion of asexual reproduction in A. niger. Finally, a genome-wide transcriptomic comparison of RNA extracted from sclerotia versus mycelia revealed major differences in gene expression. Induction of genes related to indoloterpene synthesis was confirmed and also let to the identification of a gene cluster essential for the produ

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Mammalian sex determination (male versus female) is largely controlled by genes, whereas sex differentiation (development of reproductive structures) is largely controlled by hormones. Work in the 20th century indicated that female external anatomy was a "default" pathway of development not requiring steroids, whereas male genital development required testicular testosterone plus dihydrotestosterone (DHT) made in genital skin according to a "classic" pathway. Recent work added the description of an alternative "backdoor" pathway of androgen synthesis discovered in marsupials. Unique "backdoor steroids" are found in human hyperandrogenic disorders, and genetic disruption of the pathway causes disordered male sexual development, suggesting it plays an essential role. O'Shaughnessy and colleagues now show that the principal human backdoor androgen is androsterone and provide strong evidence that it derives from placental progesterone that is metabolized to androsterone in nontesticular tissues. These studies are essential to understanding human sexual development and its disorders.

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (bad actors)-measured in prenatal blood/urine in the SELMA study-that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a typical mixture consisting of the bad actors identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose-response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of sufficient similarity to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a similar mixture risk indicator (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Objective — to study the state of puberty in child­ren with syndrome of bioinactive growth hormone (SBGH), and to assess its impact on predicted height (PH) of patients. Materials and methods. 158 children with confir­med SBGH were involved in study, including 111 boys and 47 girls in age from 3 to 17 years. The degree of puberty was estimated based on the concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in girls, and total testosterone in boys. The development of secondary sexual characteristics was evaluated according to the Tanner scale parameters. The target growth and PH were determined according to the formula of B. Blunk, as well as the bone age (BA) according to international standards (W. W. Greulich, S. P. Pyle, 1993). Results and discussion. At the time of diagnosis, 128 patients (81 %, 89 boys and 39 girls) had no evidence of puberty, and the BA had a lag for 2—3 years from the passport. In 30 children (19 %, 22 patients — boys, 8 patients — girls) the beginning of puberty was marked with significantly increased gonadotrophin and sex hormones. Children of the younger age (up to 6 years, 54 persons) had the largest lag of BA, which was 3.8 ± 0.6 years. In 74 children (at age from 7 to 12 years), in which there were no signs of puberty, the BA lagfrom the passport was 2.9 ± 0.5 years. In 30 patients with active puberty development, BA lagged behind an average of 2.3 ± 0.08 years. Patients, boys and girls, who have begun their sexual develop­ment, have significantly worse PH than patients in the prepubertal state. Conclusions. Patients with SBGH have normal sexual development with a predisposition to the early one. The feedback between patient’s age and delayed BA is noted: the younger age of children with SBGH, the greater the delay in BA they have. In children with active sexual development, significantly lower PH is determined in comparison with patients without signs of puberty. The gender difference in the defined PH is, Цель работы — изучить состояние полового развития у детей с синдромом биологически неактивного гормона роста (СБНГР) и оценить его влияние на прогнозируемый рост (ПР) пациентов. Материалы и методы. В исследовании приняли участие 158 человек с подтвержденным СБНГР, среди них 111 мальчиков и 47 девочек в возрасте от 3 до 17 лет. Оценка степени полового созревания проводилась на основании содержания лютеинизирующего гормона, фолликулостимулирующего гормона, эстрадиола у девочек, тестостерона общего у мальчиков. Развитие вторичных половых признаков оценивали по параметрам шкалы Таннера. Опре­деляли целевой рост (ЦР) и ПР по формуле В. Бланка, а также костный возраст (КВ) по международным стандартам (WW Greulich, SP Pyle, 1993). Результаты и обсуждение. На момент постановки диагноза у 128 пациентов (81 %, 89 мальчиков и 39 девочек) признаки полового созревания отсутствовали, КВ отставал на 2—3 года от паспортного. У 30 детей (19 %, 22 больных — мальчики, 8 — де­­вочки) отмечали начало полового созревания с достоверно повышенными показателями гонадотропинов и половых гормонов. Дети младшего возраста (до 6 лет, 54 человека) имели наибольшее отставание КВ, которое составляло 3,8 ± 0,6 лет. У 74 детей (в возрасте от 7 до 12 лет), у которых не было признаков начала полового созревания, отставание КВ от паспортного составило 2,9 ± 0,5 лет. У 30 больных с активным пубертатом КВ отставал в среднем на 2,3 ± 0,08 лет. Пациенты (как юноши, так и девушки), у которых уже началось половое развитие, имеют значительно худший ПР, чем больные, которые находятся в допубертатном состоянии. Выводы. Пациенты с СБНГР имеют нормальное половое развитие со склонностью к раннему. Отме­чается обратная связь между возрастом пациентов и задержкой КВ: чем моложе дети с СБНГР, тем большую задержку КВ они имеют. У детей с активным половым развитием определяется ПР достоверно ниже в сравнении с больными без признаков пубертации. Гендерной разницы в определении ПР в зависимости от полового созревания не о, Мета роботи — вивчити стан статевого дозрівання дітей із синдромом біологічно неактивного гормону росту (СБНГР) та оцінити його вплив на прогнозований зріст (ПЗ) пацієнтів. Матеріали та методи. У дослідженні взяли участь 158 осіб із підтвердженим СБНГР, серед них 111 хлопців та 47 дівчат віком від 3 до 17 років. Оцінка ступеня статевого дозрівання проводилася на підставі вмісту лютеїнізуючого гормону, фолі­кулостимулюючого гормону, естрадіолу в дівчат, тестостерону загального у хлопців. Розвиток вторинних статевих ознак оцінювали за параметрами шкали Таннера. Визначали цільовий зріст та ПЗ за формулою Блунка В., а також кістковий вік (КВ) за міжнародними стандартами (WW Greulich, SP Pyle, 1993). Результати та обговорення. На момент визначення діагнозу у 128 пацієнтів (81 %, 89 хлопців та 39 дівчат) ознаки статевого дозрівання були відсутні, КВ мав відставання на 2—3 роки від паспортного. У 30 дітей (19 %, 22 хворих — хлопці, 8 пацієнтів — дівчата) відзначали початок статевого дозрівання з достовірно підвищеними показни­ками гонадотропінів та статевих гормонів. Діти молодшого віку (до 6 ро­­ків, 54 особи) мали найбільше відставання КВ, яке складало 3,8 ± 0,6 років. У 74 дітей (віком від 7 до 12 років), у яких не було ознак початку статевого дозрівання, відставання КВ від паспортного становило 2,9 ± 0,5 років. У 30 хворих з активним пубертатним розвитком КВ відставав середнім показником 2,3 ± 0,08 років. Пацієнти (як хлопці, так і дівчата), у яких уже розпочався статевий розвиток, мають значно гірший ПЗ, ніж хворі, що перебувають у допубертатному стані. Висновки. Пацієнти із СБНГР мають нормальний статевий розвиток зі схильністю до раннього. Зазначено зворотній зв’язок між віком пацієнтів та затримкою КВ: чим менший вік дітей із СБНГР, тим більшу затримку КВ вони мають. У дітей з активним статевим розвитком визначається достовірно нижчий ПЗ у порівнянні із хворими без ознак пубертації. Гендерна різниця у визначенні ПЗ в залежності від статевого дозрівання не зазначена

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Mammalian sex determination (male versus female) is largely controlled by genes, whereas sex differentiation (development of reproductive structures) is largely controlled by hormones. Work in the 20th century indicated that female external anatomy was a "default" pathway of development not requiring steroids, whereas male genital development required testicular testosterone plus dihydrotestosterone (DHT) made in genital skin according to a "classic" pathway. Recent work added the description of an alternative "backdoor" pathway of androgen synthesis discovered in marsupials. Unique "backdoor steroids" are found in human hyperandrogenic disorders, and genetic disruption of the pathway causes disordered male sexual development, suggesting it plays an essential role. O'Shaughnessy and colleagues now show that the principal human backdoor androgen is androsterone and provide strong evidence that it derives from placental progesterone that is metabolized to androsterone in nontesticular tissues. These studies are essential to understanding human sexual development and its disorders.

The existence of play, a form of behaviour without obvious benefits to survival or reproduction, is a long-standing ethological mystery. Experiments in which socially deprived juvenile male mammals develop into sexually incompetent adults, along with widespread sexual dimorphism in rough-and-tumble play (R&T), suggest that R&T may prepare juvenile males for adult sexual behaviour. To test this hypothesis, we conducted a longitudinal study of American mink, Neovison vison, on two farms, with two cohorts each. For males (N = 121), we predicted that individuals with the highest frequencies of rough-and-tumble play as juveniles (10–20 weeks old) would, as adults, show shorter latencies to bite females' necks and to begin copulating, and copulate for longer durations. On one farm, we conducted a pilot study of females (N = 10) as a preliminary test of the hypothesis that R&T also prepares females for adult sexual behaviour. Here, our predictions were the opposite of those for males, since abilities to limit the number or duration of copulations could allow females to exercise pre- or postcopulatory mate choice. In total, we observed 1669 male–female encounters and 1004 separate copulations. As predicted, frequent juvenile R&T predicted long-lasting copulations in adult males and longer latencies to copulate in adult females. This was true specifically of rough-and-tumble play itself, independently of general activity levels and, among a subset of 32 males reared in environmentally enriched housing, also independently of solitary object play. To our knowledge, this is the first demonstration that juvenile rough-and-tumble play predicts adult sexual behaviour in any species. Further research is required to test whether our results for females can be replicated, and, importantly, to determine whether play truly has a causal role in either of these correlational relationships.

Insects are the only known animals in which sexual differentiation is controlled by sex-specific splicing. The doublesex transcription factor produces distinct male and female isoforms, which are both essential for sex-specific development. dsx splicing depends on transformer, which is also alternatively spliced such that functional Tra is only present in females. This pathway has evolved from an ancestral mechanism where dsx was independent of tra and expressed and required only in males. To reconstruct this transition, we examined three basal, hemimetabolous insect orders: Hemiptera, Phthiraptera, and Blattodea. We show that tra and dsx have distinct functions in these insects, reflecting different stages in the changeover from a transcription-based to a splicing-based mode of sexual differentiation. We propose that the canonical insect tra-dsx pathway evolved via merger between expanding dsx function (from males to both sexes) and narrowing tra function (from a general splicing factor to dedicated regulator of dsx).

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans. Here, we identified four DSD patients with overlapping duplications or deletions upstream of SOX9. Bioinformatic analysis identified three putative enhancers for SOX9 that responded to different combinations of testis-specific regulators. All three enhancers showed synergistic activity and together drive SOX9 in the testis. This is the first study to identify SOX9 enhancers that, when duplicated or deleted, result in 46,XX or 46,XY sex reversal, respectively. These enhancers provide a hitherto missing link by which SRY activates SOX9 in humans, and establish SOX9 enhancer mutations as a significant cause of DSD.Copyright © 2018, The Author(s).

One main source of sexual socialization lies within family interactions. Especially sexuality-specific parenting may determine adolescents’ sexual development—adolescents’ sexual behavior and sexual risk behavior, sexualized media consumption and permissive sexual attitudes—to a significant extent, but different ideas exist about how this works. In this longitudinal study, we examined two hypotheses on how sexuality-specific parenting—parenting aimed specifically at children’s sexual attitudes and behaviors—relates to adolescents’ sexual development. A first buffer hypothesis states that parents’ instructive media discussions with their children—called instructive mediation—buffers the effect of sexualized media consumption on adolescents’ sexual attitudes and behavior and, vice versa, the effect of adolescents’ sexual attitudes and behavior on sexualized media consumption. A second brake hypothesis states that parents, by communicating love-and-respect oriented sexual norms, slow down adolescents’ development toward increased sexualized media use, permissive sexual attitudes, and sexual behavior and sexual risk behavior. Using four-wave longitudinal data from 514 Dutch adolescents aged 13–16 years (49.8% female), we found evidence to support a brake effect. More frequent parental communication of love-and-respect oriented sexual norms was associated with less permissive sexual attitudes and, for boys, with less advanced sexual behavior and a less rapid increase in sexual risk behavior. Parents’ instructive mediation regarding adolescents’ sexualized media consumption was associated with less permissive sexual attitudes at baseline, but only for girls. No systematic evidence emerged for a buffer effect of parents’ instructive mediation. In conclusion, although our data seem to suggest that parent–child communication about sex is oftentimes “after the fact”, we also find that more directive parental communication that conveys love-and-respect oriented sexual norms br

Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans. Here, we identified four DSD patients with overlapping duplications or deletions upstream of SOX9. Bioinformatic analysis identified three putative enhancers for SOX9 that responded to different combinations of testis-specific regulators. All three enhancers showed synergistic activity and together drive SOX9 in the testis. This is the first study to identify SOX9 enhancers that, when duplicated or deleted, result in 46,XX or 46,XY sex reversal, respectively. These enhancers provide a hitherto missing link by which SRY activates SOX9 in humans, and establish SOX9 enhancer mutations as a significant cause of DSD.Copyright © 2018, The Author(s).

The elegant developmental biology experiments conducted in the 1940s by French physiologist Alfred Jost demonstrated that the sexual phenotype of a mammalian embryo depended whether the embryonic gonad develops into a testis or not. In humans, anomalies in the processes that regulate development of chromosomal, gonadal or anatomic sex result in a spectrum of conditions termed Disorders/Differences of Sex Development (DSD). Each of these conditions is rare, and understanding of their genetic etiology is still incomplete. Historically, DSD diagnoses have been difficult to establish due to the lack of standardization of anatomical and endocrine phenotyping procedures as well as genetic testing. Yet, a definitive diagnosis is critical for optimal management of the medical and psychosocial challenges associated with DSD conditions. The advent in the clinical realm of next-generation sequencing methods, with constantly decreasing price and turnaround time, has revolutionized the diagnostic process. Here we review the successes and limitations of the genetic methods currently available for DSD diagnosis, including Sanger sequencing, karyotyping, exome sequencing and chromosomal microarrays. While exome sequencing provides higher diagnostic rates, many patients still remain undiagnosed. Newer approaches, such as whole-genome sequencing and whole-genome mapping, along with gene expression studies, have the potential to identify novel DSD-causing genes and significantly increase total diagnostic yield, hopefully shortening the patients journey to an accurate diagnosis and enhancing health-related quality-of-life outcomes for patients and families.

The onset of adolescence is a time of profound changes in motivation, cognition, behavior, and social relationships. Existing neurodevelopmental models have integrated our current understanding of adolescent brain development; however, there has been surprisingly little focus on the importance of adolescence as a sensitive period for romantic and sexual development. As young people enter adolescence, one of their primary tasks is to gain knowledge and experience that will allow them to take on the social roles of adults, including engaging in romantic and sexual relationships. By reviewing the relevant human and animal neurodevelopmental literature, this paper highlights how we should move beyond thinking of puberty as simply a set of somatic changes that are critical for physical reproductive maturation. Rather, puberty also involves a set of neurobiological changes that are critical for the social, emotional, and cognitive maturation necessary for reproductive success. The primary goal of this paper is to broaden the research base and dialogue about adolescent romantic and sexual development, in hopes of advancing understanding of sex and romance as important developmental dimensions of health and well-being in adolescence.

Background. To study peculiarities of physical and sexual development and menstrual function in girls from the military conflict area in the Eastern part of the country who receive treatment in the State Institution “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”. Materials and methods. 192 girls aged 7–17 years who had been admitted to various departments of the institute were included in the study. An anthropometric study was conducted using common techniques and centile tables. Sexual development was identified by intensity of secondary sexual characteristics according to J. Tanner classification. A time of menarche and peculiarities of the menstrual function development were eva­luated. Results. Reproductive potential of girls from the military conflict area shows a high level of deviations manifesting in deterioration in physical development, impaired sexual maturation, and abnormal menstrual function. Whereas, it appears to be poorer in girls-victims of the military conflict in the Eastern Ukraine than in girls from the general population. Peculiarities of physical and sexual development and abnormal menstrual function were identified in girls from the immediate armed conflict area, grey area, and in displaced persons. Conclusions. Studying and understanding the problems of children-victims of the military conflict, dynamic evaluation of their physical, sexual, and menstrual function development are necessary to create effective support programs for them. This will enable to start treatment measures aimed at restoration of their reproductive potential and prevention of reproductive losses in the future., Актуальность. Здоровье детей и подростков является наиболее ярким показателем благополучия нации, состояния экономической и социальной сферы. Поэтому особенно остро в настоящее время стоит вопрос о раннем выявлении и своевременном лечении девочек с нарушениями полового развития и расстройствами менструальной функции, особенно подвергшихся сильным психоэмоциональным воздействиям. Пребывание человека в травматической ситуации не ограничивается развитием психологических последствий, страдает также физическое, соматическое, репродуктивное здоровье. Все это требует комплексных и междисциплинарных исследований. Цель исследования: изучение особенностей физического, полового развития и менструальной функции у девочек из зоны военного конфликта на востоке страны, находящихся на лечении в ГУ «Институт охраны здоровья детей и подростков НАМН Украины». Материалы и методы. Обследованы 192 девочки 7–17 лет, поступившие в различные отделения института. Проводилось антропометрическое исследование по общепринятым методикам с использованием центильных таблиц. Половое развитие определялось по интенсивности развития вторичных половых признаков согласно классификации J. Tanner. Оценивались время старта менструальной функции и особенности ее становления. Результаты. Репродуктивный потенциал девочек из зоны военного конфликта имеет высокий уровень отклонений, выражающийся в ухудшении физического развития, расстройствах полового созревания и нарушениях менструальной функции. Причем у девочек, пострадавших в результате боевых действий на востоке страны, он выглядит хуже, чем у школьниц из основной популяции. Выявлены особенности физического, полового развития и нарушений менструальной функции у девочек из зоны непосредственно вооруженного конфликта, серой зоны и переселенцев. Выводы. Изучение и понимание проблем детей, пострадавших в результате военного конфликта, динамическая оценка их физического, полового развития, становления менструальной функции необходимо для разработки эффективных п, Актуальність. Здоров’я дітей та підлітків є найбільш яскравим показником благополуччя нації, стану економічної та соціальної сфери. Тому особливо гостро на даний час стоїть питання щодо раннього виявлення і своєчасного лікування дівчаток з порушеннями статевого розвитку та розладами менструальної функції, особливо тих, які зазнали сильний психоемоційний вплив. Перебування людини в травматичній ситуації не обмежується розвитком психологічних наслідків, страждає також фізичне, соматичне, репродуктивне здоров’я. Все це вимагає комплексних і міждисциплінарних досліджень. Мета дослідження: вивчення особливостей фізичного, статевого розвитку та менструальної функції у дівчаток із зони військового конфлікту на сході країни, які знаходяться на лікуванні в ДУ «Інститут охорони здоров’я дітей та підлітків НАМН України». Матеріали та методи. Обстежено 192 дівчинки 7–17 років, які надійшли в різні відділення інституту. Проводились антропометричні дослідження за загальноприйнятими методиками з використанням центильних таблиць. Статевий розвиток визначався за інтенсивністю розвитку вторинних статевих ознак відповідно до класифікації J. Tanner. Оцінювалися час старту менструальної функції та особливості її становлення. Результати. Репродуктивний потенціал дівчаток із зони військового конфлікту має високий рівень відхилень, що виражається в погіршенні фізичного розвитку, розладах статевого дозрівання і порушеннях менструальної функції. Причому у дівчаток, які постраждали в результаті бойових дій на сході країни, він виглядає гірше, ніж у школярок з основної популяції. Виявлено особливості порушень фізичного, статевого розвитку та менструальної функції у дівчаток із зони безпосередньо збройного конфлікту, сірої зони і переселенців. Висновки. Вивчення і розуміння проблем дітей, які постраждали в результаті військового конфлікту, динамічна оцінка їх фізичного, статевого розвитку, становлення менструальної функції необхідні для розробки ефективних програм допомоги цим дітям. Це дасть м

The onset of adolescence is a time of profound changes in motivation, cognition, behavior, and social relationships. Existing neurodevelopmental models have integrated our current understanding of adolescent brain development; however, there has been surprisingly little focus on the importance of adolescence as a sensitive period for romantic and sexual development. As young people enter adolescence, one of their primary tasks is to gain knowledge and experience that will allow them to take on the social roles of adults, including engaging in romantic and sexual relationships. By reviewing the relevant human and animal neurodevelopmental literature, this paper highlights how we should move beyond thinking of puberty as simply a set of somatic changes that are critical for physical reproductive maturation. Rather, puberty also involves a set of neurobiological changes that are critical for the social, emotional, and cognitive maturation necessary for reproductive success. The primary goal of this paper is to broaden the research base and dialogue about adolescent romantic and sexual development, in hopes of advancing understanding of sex and romance as important developmental dimensions of health and well-being in adolescence.

The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that co-operates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosom

Arguments by lgbti advocates and the assertion of the rights of individuals with sexual development differences, point toward a growing debate on the existence of a new paradigm around the traditional binary concept of malefemale genders. In Colombian Law, this discussion extends to the field of the State liability for sex reassignment or modifying genitals surgeries performed in minors, without their informed consent. Once identified the grounds for the State liability, this paper shows the need for additional measures of reparation, beyond the award of economic damages, by means of concerted actions of the executive and legislative branches, intended to prevent discrimination, repetition and to dignify these individuals, Los argumentos esbozados por los defensores y activistas de la comunidad lgtbi, y la reivindicación de los derechos de las personas con diferencias de desarrollo sexual, conducen a reflexionar sobre la aparición de un nuevo paradigma en la concepción binaria tradicional masculino-femenino. En el derecho colombiano, este debate se extiende al campo de la responsabilidad extracontractual del Estado a favor de aquellas personas que, durante su niñez, fueron intervenidas quirúrgicamente sin su consentimiento informado para la reasignación de sexo o modificación de sus genitales. Una vez identificados los fundamentos de la responsabilidad estatal, la presente investigación pone en evidencia la necesidad de adoptar medidas adicionales de reparación, más allá de lo económico, que involucren acciones concertadas del ejecutivo y del legislador con miras a garantizar la no discriminación, la no repetición y la dignificación de estas personas

There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Mullerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Mullerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Mullerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Mullerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.

There is an increasing concern regarding the risks associated with developmental exposure to endocrine disrupting chemicals and the consequences for reproductive capability. The present study aimed to refine the Xenopus (Silurana) tropicalis test system for developmental reproductive toxicity by characterising molecular and histological features of sexual development, and to explore effects of exposure to the progestagen levonorgestrel (LNG). Larvae were exposed to LNG (0, 3, 30, 300 ng/L) over the first three weeks of development, encompassing the beginning of gonadal differentiation. mRNA levels of amh (anti-Mullerian hormone), amhr2 (amh receptor 2), ipgr (intracellular progesterone receptor), mpgr beta (membrane progesterone receptor beta), and cyp19a1 (cytochrome p450 19a1) were quantified in larvae and juveniles (4 weeks post-metamorphosis). Relative cyp19a1 and amh expression was used as a molecular marker for phenotypic sex of larvae. Gonadal and Mullerian duct development were characterised histologically in juveniles. Compared to controls, LNG exposure increased the expression of amh and ipgr in male larvae. In juveniles, mpgr beta expression was increased in both sexes and amhr2 expression was decreased in males, implying persistent effects of developmental progestagen exposure on amh and pgr expression signalling. No effects of LNG on the gonadal or Mullerian duct development were found, implying that the exposure window was not critical with regard to these endpoints. In juveniles, folliculogenesis had initiated and the Mullerian ducts were larger in females than in males. This new knowledge on sexual development in X. tropicalis is useful in the development of early life-stage endpoints for developmental reproductive toxicity.

The existence of play, a form of behaviour without obvious benefits to survival or reproduction, is a longstanding ethological mystery. Experiments in which socially deprived juvenile male mammals develop into sexually incompetent adults, along with widespread sexual dimorphism in rough-and-tumble play (R&T), suggest that R&T may prepare juvenile males for adult sexual behaviour. To test this hypothesis, we conducted a longitudinal study of American mink, Neovison vison, on two farms, with two cohorts each. For males (N ¼ 121), we predicted that individuals with the highest frequencies of rough-andtumble play as juveniles (10e20 weeks old) would, as adults, show shorter latencies to bite females' necks and to begin copulating, and copulate for longer durations. On one farm, we conducted a pilot study of females (N ¼ 10) as a preliminary test of the hypothesis that R&T also prepares females for adult sexual behaviour. Here, our predictions were the opposite of those for males, since abilities to limit the number or duration of copulations could allow females to exercise pre- or postcopulatory mate choice. In total, we observed 1669 maleefemale encounters and 1004 separate copulations. As predicted, frequent juvenile R&T predicted long-lasting copulations in adult males and longer latencies to copulate in adult females. This was true specifically of rough-and-tumble play itself, independently of general activity levels and, among a subset of 32 males reared in environmentally enriched housing, also independently of solitary object play. To our knowledge, this is the first demonstration that juvenile rough-and-tumble play predicts adult sexual behaviour in any species. Further research is required to test whether our results for females can be replicated, and, importantly, to determine whether play truly has a causal role in either of these correlational relationships.

Den unga människan ska utforska och utveckla sin egen sexualitet och identitet och ett viktigt stöd i denna process är skolan. Syftet med studien var att undersöka vilket kunskapsbehov inom sex – och samlevnad eleverna uttryckte i årskurs tre på gymnasiet. Likaledes undersöktes om det går att utifrån bakgrundsfaktorer urskilja särskilda grupper av gymnasieelever årskurs tre som uttryckte ett behov av sex– och samlevnadsundervisning. Metod: Studien genomfördes som en enkätundersökning med 248 elever, 154 män och 92 kvinnor (Mdn=18 år). Resultatet visade att det fanns ett kunskapsbehov inom särskilda områden, till exempel hur man får en relation att fungera bra, hur könssjukdomar smittar och hur man undviker att en kondom går sönder. Kvinnor samt elever på högskoleförberedande program uttryckte ett större kunskapsbehov än män och elever på yrkesförberedande program. Slutsats: Det finns ett kunskapsbehov hos särskilda grupper och det behövs sålunda mer forskning för att kunna förstå de bakomliggande psykologiska aspekterna av detta behov., The adolescens is about to explore and develop its sexuality and identity and the school is a big support in this process. The purpose of this study was to examine which knowledge of sex and coexistence students in high school desired. The intention was likewise to examine if backgrounds variables could explain differences in requested knowledge. Method: The study was conducted through a questionnaire survey with 248 participants, whereof 154 were men and 92 were women (Mdn=18). The result demonstrated that students desired more knowledge in specific areas, for example how to managed a relationship, how sexually transmitted diseases (STD) infect and how to avoid the condom bursting. Women and students at pre-university programs expressed to a greater degree that they desired more knowledge then men and students at vocational programs. The conclusion indicated that specific groups requested more knowledge and more research requires to understand the underlying psychological aspects of the requirement.

Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans.

Den unga människan ska utforska och utveckla sin egen sexualitet och identitet och ett viktigt stöd i denna process är skolan. Syftet med studien var att undersöka vilket kunskapsbehov inom sex – och samlevnad eleverna uttryckte i årskurs tre på gymnasiet. Likaledes undersöktes om det går att utifrån bakgrundsfaktorer urskilja särskilda grupper av gymnasieelever årskurs tre som uttryckte ett behov av sex– och samlevnadsundervisning. Metod: Studien genomfördes som en enkätundersökning med 248 elever, 154 män och 92 kvinnor (Mdn=18 år). Resultatet visade att det fanns ett kunskapsbehov inom särskilda områden, till exempel hur man får en relation att fungera bra, hur könssjukdomar smittar och hur man undviker att en kondom går sönder. Kvinnor samt elever på högskoleförberedande program uttryckte ett större kunskapsbehov än män och elever på yrkesförberedande program. Slutsats: Det finns ett kunskapsbehov hos särskilda grupper och det behövs sålunda mer forskning för att kunna förstå de bakomliggande psykologiska aspekterna av detta behov., The adolescens is about to explore and develop its sexuality and identity and the school is a big support in this process. The purpose of this study was to examine which knowledge of sex and coexistence students in high school desired. The intention was likewise to examine if backgrounds variables could explain differences in requested knowledge. Method: The study was conducted through a questionnaire survey with 248 participants, whereof 154 were men and 92 were women (Mdn=18). The result demonstrated that students desired more knowledge in specific areas, for example how to managed a relationship, how sexually transmitted diseases (STD) infect and how to avoid the condom bursting. Women and students at pre-university programs expressed to a greater degree that they desired more knowledge then men and students at vocational programs. The conclusion indicated that specific groups requested more knowledge and more research requires to understand the underlying psychological aspects of the requirement.

In this study, we tested two competing explanations of the previously established link between early female puberty and sexual harassment in early adolescence. The sample included 680 seventh-grade Swedish girls (Mage = 13.40, SD = .53). Findings revealed that looking more sexually mature and being sexually active mediated the link between pubertal timing and sexual harassment. The magnitude of the indirect effect through sexually mature appearance was greater than that through engagement in sexual behaviors. Apparently, early-maturing girls are sexually harassed as a result of natural and normative sexual development, which happens earlier than for most of their peers. The findings have clear implications for prevention of sexual harassment in adolescence, Funding Agency:Swedish Crime Victim Compensation and Support Authority 02847/2013

This dissertation investigated how sex-related online behaviors shape sexual developmental processes in adolescence, and how Internet use and online behaviors are embedded in other, offline influencing systems in young people's lives.The overarching aims of the eight empirical studies, which utilized a developmental, contextual, and multi-method perspective, were to: (1) Establish the prevalence and development of different sex-related online behaviors in adolescence, as well as their longitudinal associations with adolescents' sexual cognitions, emotions, and behaviors; (2) Identify mechanisms underlying effects of sex-related Internet use, and individual differences in patterns of sex-related online behaviors and the factors that predict these differences; (3) Gain more in-depth insight into the content adolescents are exposed to, create, and distribute when engaging in sex-related online behaviors, as well as their own motives, perceptions, and reflections regarding such content and behaviors. The results of this dissertation suggest that, for the general adolescent population, engagement in most sex-related online behaviors (use of sexually explicit Internet material, sexual information seeking, and cybersex) is not widespread or excessive. An exception to the generally low engagement in these behaviors is adolescents’ use of social networking sites. This highly popular social activity is not explicitly sexual in genre, yet may function as an important context for adolescents to form and evaluate conceptions of sexuality, engage in sexual communication, and explore and portray their own sexual identity. Although mean engagement in sex-related online behaviors was found to be less prevalent than often assumed or feared, the studies in this dissertation confirm theoretical assumptions by showing that sex-related online behaviors have the potential to shape adolescents’ sexual cognitions, behaviors, and emotions over ti