Sex-linked neuroanatomical basis of human altruistic cooperativeness

Human altruistic cooperativeness, one of the most important components of our highly organized society, is along with a greatly enlarged brain relative to body size a spectacular outlier in the animal world. The "social-brain hypothesis" suggests that human brain expansion reflects an increased necessity for information processing to create social reciprocity and cooperation in our complex society. The present study showed that the young adult females (n = 66) showed greater Cooperativeness as well as larger relative global and regional gray matter volumes (GMVs) than the matched males (n = 89), particularly in the social-brain regions including bilateral posterior inferior frontal and left anterior medial prefrontal cortices. Moreover, in females, higher cooperativeness was tightly coupled with the larger relative total GMV and more specifically with the regional GMV in most of the regions revealing larger in female sex-dimorphism. The global and most of regional correlations between GMV and Cooperativeness were significantly specific to female. These results suggest that sexually dimorphic factors may affect the neurodevelopment of these "social-brain" regions, leading to higher cooperativeness in females. The present findings may also have an implication for the pathophysiology of autism; characterized by severe dysfunction in social reciprocity, abnormalities in social-brain, and disproportionately low probability in females.

Strength training combined with plyometric jumps in adults: sex differences in fat-bone axis adaptations

[EN] Leptin and osteocalcin play a role in the regulation of the fat-bone axis and may be altered by exercise. To determine whether osteocalcin reduces fat mass in humans fed ad libitum and if there is a sex dimorphism in the serum osteocalcin and leptin responses to strength training, we studied 43 male (age 23.9 2.4 yr, mean +/- SD) and 23 female physical education students (age 23.2 +/- 2.7 yr). Subjects were randomly assigned to two groups: training (TG) and control (CG). TG followed a strength combined with plyometric jumps training program during 9 wk, whereas the CG did not train. Physical fitness, body composition (dual-energy X-ray absorptiometry), and serum concentrations of hormones were determined pre- and posttraining. In the whole group of subjects (pretraining), the serum concentration of osteocalcin was positively correlated (r = 0.29-0.42, P < 0.05) with whole body and regional bone mineral content, lean mass, dynamic strength, and serum-free testosterone concentration (r = 0.32). However, osteocalcin was negatively correlated with leptin concentration (r = -0.37), fat mass (r = -0.31), and the percent body fat (r = -0.44). Both sexes experienced similar relative improvements in performance, lean mass (+4-5%), and whole body (+0.78%) and lumbar spine bone mineral content (+1.2-2%) with training. Serum osteocalcin concentration was increased after training by 45 and 27% in men and women, respectively (P < 0.05). Fat mass was not altered by training. Vastus lateralis type II MHC composition at the start of the training program predicted 25% of the osteocalcin increase after training. Serum leptin concentration was reduced with training in women. In summary, while the relative effects of strength training plus plyometric jumps in performance, muscle hypertrophy, and osteogenesis are similar in men and women, serum leptin concentration is reduced only in women. The osteocalcin response to strength training is, in part, modulated by the muscle phenotype (MHC isoform composition). Despite the increase in osteocalcin, fat mass was not reduced.

Odontometric analysis of molars for sex determination

Aim: To investigate the existence of sexual dimorphism between the first and second permanent molars. Methods: A cross-sectional, observational, blind study using comparative and statistical descriptive procedures. The sample included 50 pairs of plaster casts from undergraduate dental students (25 men/25 women) from the Federal University of Paraíba, João Pessoa/PB, Brazil, aged 20-26 years. Odontometric measurements of first and second maxillary/mandibular, right/left permanent molars were performed. Mesiodistal (MD) and buccolingual/palatal (BL/BP) widths and the distance between the lingual cusps of corresponding molars in opposite quadrants, were measured. The data were analyzed by Student’s t test and ANOVA with Bonferroni (p≤0.05). Results: The crowns of all first molars were statistically larger in men than in women (p<0.05). Maxillary and mandibular left second molars (#27 and #37) did not differ in their MD widths (p=0.66, p=0.75), whereas mandibular left and right second molars (#37 and #47) showed statistically different BL widths (p=0.007 and p=0.008). As to the distance between the lingual cusps, only the first left-to-right mandibular molars (#36-46) showed no sex dimorphism (p=0.107). Conclusions: Molars are larger in males than in females. Individually, first molars demonstrated higher evidence of sex distinction than second molars.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

OBJECTIVE: To examine the role of androgens on birth weight in genetic models of altered androgen signalling. SETTING: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). PATIENTS: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. MAIN OUTCOME MEASURES: Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. RESULTS: Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CONCLUSION: CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.

Estudo dos efeitos da exposição materna à nicotina na lactação sobre a função da medula adrenal e dos adipócitos de ratos machos e fêmeas

Alterações nutricionais, hormonais e ambientais nos períodos críticos do desenvolvimento como a gestação e/ou lactação podem influenciar a estrutura e a fisiologia de órgãos e tecidos, predispondo ao aparecimento de doenças na vida adulta. Esse fenômeno é conhecido como programação metabólica. O fumo materno na gestação/lactação tem sido associado ao sobrepeso/obesidade na infância e na vida adulta em ambos os sexos. Porém, estudos evidenciam diferenças entre os gêneros em resposta a exposição à nicotina. Já foi demonstrado que muitas mulheres param de fumar na gestação, mas a maioria destas volta a fumar na lactação. Anteriormente, mostramos que machos adultos cujas mães foram expostas à nicotina na lactação, desenvolveram obesidade central, hiperleptinemia e hipotireoidismo. Como a nicotina afeta a função adrenal e como catecolaminas e glicocorticóides têm efeitos bem conhecidos sobre o tecido adiposo, avaliamos a função da medula adrenal e o conteúdo de leptina no tecido adiposo e músculo de machos e fêmeas cujas mães foram expostas à nicotina na lactação. Dois dias pós-parto, implantamos minibombas osmóticas nas ratas lactantes dividas em: NIC infusão de nicotina (6mg/Kg/dia s.c.) por 14 dias, e C infusão de salina pelo mesmo período. Estas lactantes foram divididas de acordo com o sexo das proles. O sacrifício das proles de ambos os sexos ocorreu aos 15 (fim da exposição à nicotina) e 180 dias de vida. Aos 15 dias, os machos da prole NIC apresentaram aumento de MGV absoluta e relativa ao peso corporal (+72% e +73% respectivamente), hiperleptinemia (+35%), hipercorticosteronemia (+67%), maior peso adrenal (+39%), conteúdo de catecolaminas totais (absoluto: +69% e relativo: +41%), embora diminuição da enzima TH (-33%). Quando adultos, os machos programados exibiram maior massa corporal (+10%), MGV absoluta (+47%) e relativa (+33%), além de hiperleptinemia (+41%) e maior conteúdo de leptina no TAV (+23%). Esses animais também apresentaram hipercorticosteronemia (+77%), maior conteúdo de catecolaminas totais absoluto e relativo (+79% e +89% respectivamente) e de TH (+38%) embora tenham menor secreção de catecolaminas in vitro estimulada por cafeína (-19%) e maior expressão do ADRB3 no TAV (+59%). Em relação as fêmeas da prole NIC aos 15 dias de vida, estas apresentaram menor massa corporal (-6%) e hiperleptinemia (+41%) embora sem alteração da MGV. Aos 180 dias, as fêmeas da prole NIC apresentaram menor conteúdo de leptina no TAS (-46%) e maior conteúdo de leptina no músculo solear (+22%) e diminuição da expressão do ADRB3 no TAV (-39%). Concluímos que a nicotina materna afeta ambos, medula adrenal e tecido adiposo de forma gênero dependente, tanto em curto prazo (quando a nicotina está presente no leite materno), quanto em longo prazo (repercussões na vida adulta). De forma geral, as fêmeas da prole NIC apresentam alterações mais discretas do que os machos em ambos os períodos estudados.

A worldwide survey of chronic cough: A manifestation of enhanced somatosensory response:A manifestation of enhanced somatosensory response

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10 032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60-69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation.

Noradrenaline, but not neuropeptide Y, is elevated in cerebrospinal fluid from the third cerebral ventricle following audiovisual stress in gonadectomised rams and ewes

There are sex differences in the activation of the hypothalamo-pituitary-adrenal axis in response to stress, but the source of these differences is unknown. The hypothalamo-pituitary-adrenal axis is regulated by corticotropin-releasing hormone and arginine-vasopressin neurones located in the paraventricular nucleus and these, in turn, are regulated by neural systems that include afferent noradrenergic and neuropeptide Y (NPY)-producing neural pathways. We tested the hypothesis that concentrations of noradrenaline and NPY will be elevated in cerebrospinal fluid (CSF) sampled from the third cerebral ventricle in response to stress, and these responses will differ in males and females. We collected concurrent samples of CSF (1 ml) from the third ventricle and blood (5 ml) from the jugular vein from gonadectomised rams (n = 7) and ewes (n = 5) at 10-min intervals for 3 h. This procedure was conducted on a day when no stress was imposed and on a day when audiovisual stress was imposed for 5 min after 1 h of sampling. Following the audiovisual stress, plasma concentrations of cortisol and CSF concentrations of noradrenaline were elevated (p < 0.05), but CSF concentrations of NPY did not change. Adrenaline was not detected in samples of CSF. The rise in plasma cortisol following the stress was greater (p < 0.05) in ewes than in rams, but there were no sex differences in the rise in noradrenaline. Basal concentrations of NPY in the CSF were higher (p < 0.05) in rams than in ewes. We conclude that the sex differences in the stress-induced activity of the hypothalamo-pituitary-adrenal axis in sheep are not likely to be due to differences in the level of noradrenergic and/or NPY input to the hypothalamus.

(Table 1) Mean statistics for acoustic parameters measured for both brown skua (Catharacta antarctica lonnbergi) sexes

Bird vocalisations are often essential for sex recognition, especially in species that show little morphological sex dimorphism. Brown skuas (Catharacta antarctica lonnbergi), which exhibit uniform plumage across both sexes, emit three main calls: the long call, the alarm call and the contact call. We tested the potential for sex recognition in brown skua calls of 42 genetically sexed individuals by analysing 8-12 acoustic parameters in the temporal and frequency domains of each call type. For every call type, we failed to find sex differences in any of the acoustic parameters measured. Stepwise discriminant function analysis (DFA) revealed that sexes cannot be unambiguously classified, with increasing uncertainty of correct classification from contact calls to long calls to alarm calls. Consequently, acoustic signalling is probably not the key mechanism for sex recognition in brown skuas.

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

Morphometric modelling of ageing in the human pubic symphysis : sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis(slice thickness: 0.5 mm, overlap: 0.1 mm) of 200 individuals of Caucasian ancestry aged 15–70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX1 (v.4.1) and quantitative analyses in Rapidform XOSTM and OsteomeasureTM. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Sexing Sirenians: Validation of Visual and Molecular Sex Determination in Both Wild Dugongs (Dugong dugon) and Florida Manatees (Trichechus manatus latirostris)

Sexing wild marine mammals that show little to no sexual dimorphism is challenging. For sirenians that are difficult to catch or approach closely, molecular sexing from tissue biopsies offers an alternative method to visual discrimination. This paper reports the results of a field study to validate the use of two sexing methods: (1) visual discrimination of sex vs (2) molecular sexing based on a multiplex PCR assay which amplifies the male-specific SRY gene and differentiates ZFX and ZFY gametologues. Skin samples from 628 dugongs (Dugong dugon) and 100 Florida manatees (Trichechus manatus latirostris) were analysed and assigned as male or female based on molecular sex. These individuals were also assigned a sex based on either direct observation of the genitalia and/or the association of the individual with a calf. Individuals of both species showed 93 to 96% congruence between visual and molecular sexing. For the remaining 4 to 7%, the discrepancies could be explained by human error. To mitigate this error rate, we recommend using both of these robust techniques, with routine inclusion of sex primers into microsatellite panels employed for identity, along with trained field observers and stringent sample handling.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Observation on the urinogenital papilla and sexual dimorphism in some Indian gobiids (Gobiidae: Teleostei)

A thorough comparative study on the urinogenital papilla and sexual dimorphism has been made for the first time in both the sexes of twelve Indian gobiids: Glassogobius giuris (Hamilton); Acentrogobius cyanomos (Bleeker); Eleotriodes muralis (Valenciennes); Parapocryptes serperaster (Richardson); Apocryptes bato (Hamilton); Scartclaos viridis (Hamilton); Boleophthalmus boddarti (Pallas), Periophthalmus schlosseri (Pallas); P. koelreuteri (Pallas); Taenioides anguillaris (Linnaeus); T. buchanani (Day); Odontamblyopus rubicundus (Hamilton). The urinogenital papilla, originating as a free muscular organ from the ventral surface of the body-wall and shortly behind anus, is present in both the sexes. It is an important organ of primary sex recognition in all species. In case of male the papilla is conical, broad at the base and in female it is either flattened, distally truncated or bluntly rounded. The presence of permanent colour mark over the specific region of the body surface is another secondary sexual character in a few species. Besides, colouration may also be a nuptial secondary sex character developed in some during peak breeding season. The enlargement and colouration of the organ is subject to seasonal variations parallel to the seasonal gonadal cycle. The histological architecture of the papilla shows a high degree of cellular specialization and an interrelationship to the urinary and genital ducts. The functional efficacy and significance of the papilla in the breeding biology of these fishes has been discussed.

Unmasking a role for sex chromosomes in gene silencing.

Several sexually dimorphic phenotypes correlate with sex-chromosome dosage rather than with phenotypic sex. New research suggests that sex chromosome dimorphism helps to regulate gene silencing.