Serum glutathione S-transferases: perinatal development, sex difference, and effect of carbon tetrachloride administration on enzyme activity in the rat.
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Aging↗
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Results for “differences of sex development”
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Molecular analysis of individuals with suspected 46,XY differences of sex development in a homogenous and understudied population.
Differences of sex development (DSD) are a group of rare congenital conditions defined by atypical chromosomal, gonadal, and/or hormonal sex. Despite advances in massively parallel sequencing (MPS), more than half of DSD cases have an unknown genetic aetiology. We recruited and analysed 21 individuals with 46,XY DSD from the Greater Middle East population using chromosomal microarray and whole exome sequencing. Participants had DSD ranging from micropenis to anorchia (absence of testes) with extra-genital features reported in four individuals (19%). Using a combination of microarray and WES, a genetic diagnosis (variants curated as likely pathogenic or pathogenic) was identified in 12/21 (57%) individuals. Microarray analysis showed two DSD participants with extra genital features had chromosomal abnormalities (48,XXXY and mosaic Y chromosomal rearrangement). Microarray also indicated a high degree of consanguinity, with extensive long contiguous stretches of homozygosity (LCSH) (>3% of the genome) in 6/21 (28.6%) individuals, all of whom received a genetic diagnosis. WES analysis revealed variants in the NR5A1 (three individuals), SRD5A2 (three individuals), TALDO1 (one individual) and AR (two individuals) genes. This includes the novel frameshift variant, c.1309del (p.Leu437Cysfs*59), in NR5A1. This study contributes to the characterisation of clinical features and molecular findings in individuals with DSD in this understudied and homogenous population and highlights the challenges with DSD diagnosis in the region. The genetic diagnoses identified may contribute to improved patient care and management.
Humans↗
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↗
DHX37 variants in patients with 46,XY disorders or differences of sex development.
Here, using whole-exome sequencing of a cohort of 17 Japanese patients with 46,XY disorders or differences of sex development, we identified two pathogenic DEAH-box helicase 37 (DHX37) variants in three patients. We also identified a patient with a likely pathogenic variant in SOX9 and a rare likely benign variant in DHX37. This Data Report highlights the genetic and phenotypic diversity of DXH37 variants.
Journal Article↗
The development of sex differences in the adrenal morphology and responsiveness in stress of rats from birth to the end of life.
The appearance and development of sex difference in the adrenal cortex of rats have been studied. Morphological and secretory differences between the adrenal cortex of female and male rats begin on the 40th day of postnatal life, when females respond in stress by a greater increase in plasma corticosterone concentration. The sex difference becomes fully manifest at the age of 55 days (females have heavier absolute and relative adrenal glands and respond to stressful stimuli by a greater increase in adrenal and plasma corticosterone concentrations). At the age of 11 to 23 months the adrenal corticosterone concentrations in stress are equal in both sexes, and the absolute adrenal weights are similar from 18.5 months until death. The body weight gain is equal in both sexes during the first 50 days of life and greater in males from day 50 to 1 year of age. After this age the body weight of males remains almost the same (315 to 322 g)8 while females continue gaining weight until the end of life (196 to 231 g). This possible causal relationship between the rhythm of growth and sex difference in the adrenal glands in rats is discussed.
Adrenal Cortex↗
Sex differences in development among young children with Down syndrome.
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Child Development↗
[Sex differences in development of circadian rhythm in the hypophyseal-adrenal cortex system].
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Adrenal Cortex Hormones↗
Characterizing 46,XY Differences of Sex Development: Novel Genetic Variants and Diagnostic Pitfalls in a Single-Center Cohort.
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17β-hydroxysteroid dehydrogenase deficiency↗
The development of sex differences in the demethylation of ethylmorphine and in its interaction with components of the hepatic microsomal cytochrome P450 system in mice.
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Aging↗
Sex differences in the developing human cortex intersect with genetic risk of neurodevelopmental disorders.
Autism is highly heritable and diagnosed more frequently in males than females. To identify neurodevelopmental processes that might present sex-biased vulnerability, we generated transcriptomic and epigenomic profiles of cell types present in the prenatally developing human cerebral cortex of 27 males and 21 females. By intersecting sex-biased molecular signatures and genes with de novo mutations in male and female autistic probands, we reveal two points of vulnerability contributing to the sex-biased penetrance in neurodevelopmental disorders (NDDs). First, we show that NDD risk genes are biased towards higher expression in females, identifying the NDD gene MEF2C as a critical transcription factor for female-biased expression. Second, we identify a significant contribution of X chromosome genes to NDD pathobiology. We construct a gene regulatory map of X-linked risk genes to enable functional studies of genetic variants that likely disrupt gene expression in the developing brains of autistic males. Together, these results point towards an outsized contribution of the X-chromosome to both the origin of sex differences in the developing human cortex and NDD vulnerability. We propose a model where female-biased vulnerability is driven by coding variation within genes while male-biased vulnerability is driven by noncoding variation in regulatory elements that affect gene expression.
Sex differences↗
Sex difference in the development of fatty liver by orotic acid.
Effects of orotic acid on liver lipid accumulation and incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein, and into serum beta-lipoprotein were studied. Male and female rats of Wistar strain were fed a semisynthetic diet supplemented with 1 per cent orotic acid for 7 days. Feeding of orotic acid induced a marked fatty liver in female rats, but not in males. In female rats, radioactivity in liver phosphatidylcholine was significantly decreased by orotic acid, and that in liver protein was slightly decreased. In male rats, incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein was unchanged between the control and the rats fed orotic acid. Radioactivity in serum beta-lipoprotein was decreased to a greater extent in female rats than in males. These results suggest that sex difference in the development of fatty liver may be due to the difference in the effect of orotic acid on liver phosphatidylcholine biosynthesis.
Acetates↗
[Hypothalamic somatostatin levels in the rat: with special references to development, nycthemeral cycle, sex difference and food restriction (author's transl)].
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Aging↗
[Sex difference in the mouse milk spots, with special reference to its development and formation (author's transl)].
As reported previously, the omental milk spots in the mouse are morphologically classified into two types; type I and II. Type II milk spots are distributed on the dorsal layer of the omentum, and they are more numerous in females than in males. The type II milk spots appear at first at 10 days of age, and then gradually increase in number equally in both sexes until 2 months. After 2 months, however, the density of the spots is significantly greater in females than in males. In male mice which have been gonadectomized at 1 month, the type II spots show remarkable increase in density, and they are as frequent as those in normal females. Administration of testosterone to gonadectomized males and normal females causes a significant decrease in density of the spots. Estriol, progesterone and gonadotropin exhibit no significant effect on the density of the spots. From the results obtained, it can be concluded that the existence of testis, namely testosterone, plays a major role in development of sex difference in type II milk spots.
Animals↗
Daydreaming in the adolescent years: instrument development, factor analysis, and sex differences.
The Imaginal Processes Inventory (IPI), originally devised for college students, was revised for use with high school students. Nineteen of the original 28 IPI daydreaming scales were used and the response format was changed. The self-report instrument was completed by a racially diverse sample of 181 ninth through eleventh grade students. Reliable application of the Revised IPI to this population was demonstrated. Distinct sex differences, not previously reported, were found showing more acceptance of daydreaming for females and more guilt and fearfulness in daydreaming for males. Factor structures were similar to previous studies, but a generally higher level of daydreaming and less uncontrolled mind wandering was found for high school students than for college students. The research suggests that personality differences between men and women could be further explored by the daydreaming instrument and that sex differences must be taken into account in further research. Use of such daydreaming data is suggested in therapeutic intervention.
Adolescent↗
Stress responses in male and female engineering students.
Male and female engineering students were studies under stress induced by a congnitive-conflict task and in a control condition spent in inactivity. The results showed that (a) in the control condition the sexes did not differ in adrenaline, noradrenaline or cortisol excretion, whereas heart rate was significantly higher in the females; (b) adrenaline excretion and heart rate increased significantly in both sexes during stress; (c) the rise in adrenaline excretion was more pronounced in the males, whereas the rise in heart rate was significantly greater in the females; (d) cortisol excretion increased significantly during stress in the male group only; and (e) self-estimates of effort and performance were consistently higher and increased more over time in the males than in the females, bu these sex differences on the subjective level were not reflected in actual performance. The interaction of biological and social factors in the development of sex differences in stress reactions is discussed.
Adult↗
Post-translational modification of proteins in the human testis development pathway.
BACKGROUND: The foetal testes produce the androgens necessary to masculinise the developing embryo and support the maturation of germ cells, that will eventually develop into sperm, thus ensuring future reproductive capacity. The testes develop from the bi-potential gonads in a highly orchestrated process resulting in the differentiation of a complex tissue with multiple cellular lineages. While recent transcriptomic and chromatin-based analyses of human foetal testes have provided an unprecedented level of insight into signalling pathways activated during this process, proteomic studies of the human foetal gonads remain limited. Proteins are active molecules and post-translational modification (PTM) of proteins influences protein activity, stability and localisation. Studies have shown that PTMs regulate critical proteins in testis development, and their disruptions are implicated in congenital disorders including differences of sex development (DSD), in which sex development is atypical. Despite this, the role and regulation of protein PTM during human testis development remains poorly understood due to limited access to human foetal gonadal tissue, a paucity of large-scale proteomics studies, and a lack of robust of human gonad in vitro models. OBJECTIVE AND RATIONALE: This review aims to provide a comprehensive analysis of validated PTMs affecting proteins critical for testicular development. We discuss PTMs with evidence for a role in normal testis development, and highlight those disrupted in DSD. We review emerging techniques, including proteomic technologies and organ modelling systems that may advance our understanding of PTMs in foetal testis development. We discuss challenges that have restricted the application of these technologies and how overcoming these will significantly improve our understanding of testis development and disease, diagnostics and patient outcomes. SEARCH METHODS: We searched PubMed and the University of Melbourne library for peer-reviewed English-language studies using keywords such as phosphorylation, SUMOylation, acetylation, ubiquitination alongside each protein of interest. PTM sites in proteins involved in testis development were identified using the PhosphoSitePlus database focusing those confirmed in in vitro or animal model studies. ClinVar and the Human Gene Mutation Database were used to identify patient variants that may disrupt PTM sites. OUTCOMES: Our review finds that proteins required for human foetal testis development are subject to extensive PTM. Several PTM sites and PTM-mediated pathways [e.g. MAPK (mitogen-activated protein kinase) pathway] are disrupted in patients with DSD or related conditions. While recent advances in proteomics technologies hold considerable promise, their application to human foetal gonads has been constrained by technical, ethical, and logistical challenges. Encouragingly, emerging high-sensitivity and low-input technologies, alongside stem cell-based approaches, offer viable pathways to overcoming these barriers. WIDER IMPLICATIONS: The relationship between gene regulation, protein expression, and cellular outcome is inherently non-linear, shaped by additional regulatory layers-most notably PTMs. The contribution of PTMs to human testis development in both typical and atypical contexts is a major knowledge gap. Addressing this gap has broad clinical and biological relevance: it may help improve genetic diagnosis or shed light on how proteins or pathways critical for testis development respond to environmental signals-an increasingly pressing question as declining global fertility rates bring testicular function under greater scrutiny. REGISTRATION NUMBER: N/A.
Humans↗
Sex differences in parent-infant interaction during free play, departure, and separation.
20 18-month-olds were observed with their mothers and 20 with their fathers in laboratory free-play, departure, and separation situations. Parent and infant behaviors were allowed to vary naturally. Although there were no parent sex or infant sex differences in infants' free-play behavior, there were parent sex X infant sex differences in parental free-play behaviors. Parents talked to, sat on the floor more with, and tended to share play more with same-sexed than opposite-sexed infants, and the patterning of free-play behaviors was different for mothers and fathers. During departure, fathers talked to the infants more than mothers. Infants were more distressed in the absence of same-sexed than opposite-sexed parents. There were infant sex X parent sex differences in the relationships between separation distress and parental free-play and departure behaviors. The implications of these findings for understanding differential roles of mothers and fathers, the development of sex differences, and the determinants of separation distress are discussed.
Father-Child Relations↗
Changes in haemoglobin and haematocrit values in children aged 6 to 13 1/2 years in Mexico City.
Levels of haemoglobin (Hb), haematocrit (Ht) and mean corpuscular haemoglobin concentration (MCHC) were determined in 523 boys and 350 girls, clinically healthy, ages 6-0 to 13-5 years, middle socio-economic class living in Mexico City. In girls no significant differences according to age were observed in Hb or MCHC; however, Ht was significantly greater at 10-5 than at 10-0 years, without subsequent modifications. In boys, Hb and Ht had a first increase between 10-5 and 11-0 years and a second rise from 12-5 years on: MCHC remained unchanged. Boys were six to twelve months behind girls in regard to Ht increase; however, Ht increased when boys and girls reached similar mean weights (34 kg), heights (138 cm) and surface areas (1-15 m2); concomitantly, they had progressed to stage 2 of sexual development. Clear sex differences began to appear at age 11-5 when boys had higher Hb and Ht values than girls. These data suggest that Hb and Ht changes in these children are not related to chronological age but can be better interpreted if compared to weight, height, surface area or stage of sexual development.
Adolescent↗