Male Onset Research Articles

ASTHMATIC CHILDREN;

Objective: To determine the knowledge and practice of parents of children withAsthma. Introduction: Asthma is a disease characterized by recurrent attacks of breathlessnessand wheezing typically begins in early childhood with an earlier onset in males than females. Lifetime prevalence of asthma is 13.5% and current asthma prevalence of 9.3% among children <18years. According to WHO 15 million disability adjusted life years (DALY) are lost annually due toAsthma. Prevalence of asthma in Pakistani children is 19%. Due to rapid industrialization andurbanization prevalence of Asthma has increased from 9 t0 20% during the last decade. Thisstudy was conducted to assess the extent of knowledge and practice which are associated withthe control of Asthma. Methodology: It was descriptive cross sectional study conducted in ED,Pediatric unit CHK. Sampling was convenience and the study duration six months. One hundredand twenty parents of asthmatic children from 4-13 years of age were selected. Results: Averageage of the children was 7.69±2.58 years (95% CI: 7.23 to 8.16) and average duration of illnesswas 3.08±2.0 years (95% CI: 2.69 to 3.45). Minimum duration was two years and maximum tenyears. One hundred and four mothers (86.7%) and 16 fathers(13.3%) participated in the study.Over all asthma knowledge and practice of parents was adequate in 20(16.7%), inadequate in46(39.3%) and average in 54(45%). Conclusions: Asthma knowledge especially about themanagement is inadequate and practices are also inappropriate in the urban population ofKarachi.

Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats

Assessment of reproductive competence is critical for understanding the impact of a treatment or genetic manipulation on the reproductive axis, also termed the hypothalamic-pituitary-gonadal axis. The reproductive axis is a key integrator of environmental and internal input adapting fertility to favorable conditions for reproduction. Prior to embarking upon a fertility study in mice and rats, sexual maturity is evaluated to exclude the possibility that the observed reproductive phenotypes are caused by delayed or absent pubertal onset. This protocol describes a non-invasive approach to assess pubertal onset in males through the determination of preputial separation, and in females through vaginal opening and first estrus. After the confirmation of the completion of puberty and the achievement of sexual maturity, a fertility study can be initiated. The procedure describes the optimal breeding conditions for mice and rats, how to set up a fertility study, and what parameters to evaluate and determine if the treatment or gene deletion has an impact on fertility.

Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases.

Exposure to vinclozolin has been shown to induce the epigenetic transgenerational inheritance of increased susceptibility to disease, and to induce transgenerational changes to the epigenome. In the current study, gestating F0 generation rats were exposed to vinclozolin, and the subsequent F1, F2 and transgenerational F3 generations were evaluated for diseases and pathologies. F1 and F2 generation rats exhibited few abnormalities. However, F3 generation rats showed transgenerational increases in testis, prostate, and kidney disease, changes in the age of puberty onset in males, and an increased obesity rate in females. Overall there was an increase in the rate of animals with disease, and in the incidence of animals with multiple diseases. The objective of the current study was to analyze the sperm epigenome of F3 generation rats with specific abnormalities and compare them to rats without those abnormalities, in an effort to find epigenetic biomarkers of transgenerational disease. Unique signatures of differential DNA methylation regions (DMRs) in sperm were found that associated with testis disease, prostate disease and kidney disease. Confounding factors identified were the presence of multiple diseases in the analysis and the limited number of animals without disease. These results further our understanding of the mechanisms governing epigenetic transgenerational inheritance, and may lead in the future to the use of epigenetic biomarkers that will help predict an individual’s susceptibility for specific diseases.

Temporal Expression Patterns of Genes Related to Sex Steroid Action in Sexually Dimorphic Nuclei During Puberty.

Sex steroids play a major role in sexually dimorphic brain development during not only the perinatal period but also the pubertal period. We previously showed that, in male mice, the estrogen receptor-α (Esr1) and aromatase (Cyp19a1) genes are essential to the sexually dimorphic formation of the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (BNSTp), but the estrogen receptor-β (Esr2) gene is not necessary. We also showed that the androgen receptor (Ar) gene is essential to the sexually dimorphic formation of the BNSTp. These genes are expressed in the AVPV and BNSTp of perinatal mice. However, it remains unknown whether these genes are expressed in the AVPV and BNSTp during puberty, and whether the expression, if any, differs by sex, age, and brain region. Here, we dissected the AVPV and BNSTp from Nissl-stained brain sections of male and female mice on postnatal day (PD) 20 (prepuberty), PD30 (puberty onset in females), PD40 (puberty onset in males), and PD60 (young adult) using a laser microdissection system. We then examined the mRNA levels of Esr1, Esr2, Cyp19a1, and Ar in these brain regions. In the AVPV, Esr1 mRNA levels were greater in females than males during PD20–60. Esr2 and Ar mRNA expressions did not differ between sexes. Ar mRNA levels were higher at PD30 than PD20. Cyp19a1 mRNA was not detected in the AVPV at PD20–60. In the BNSTp, Esr1 and Esr2 mRNA levels were higher in females than in males during PD20–60, although the mRNA levels of Cyp19a1 and Ar did not differ between sexes. Additionally, we revealed that orchiectomy at PD20 induced a failure of normal formation of the male BNSTp and testosterone replacement in the prepubertal period rescued the effect of orchiectomy at PD20. Taken together, it is suggested that pubertal testosterone transported to the AVPV is not converted to estradiol there and does not act via ESR1 and ESR2. By contrast, the formation of the male BNSTp may be affected by testicular testosterone during puberty via AR and/or via ESR1 after conversion to estradiol by CYP19A1.

Neonatal Overnutrition Increases Testicular Size and Expression of Luteinizing Hormone β-Subunit in Peripubertal Male Rats.

Proper nutrition is important for growth and development. Maturation of the reproductive axis and the timing of pubertal onset can be delayed when insufficient nutrition is available, or possibly advanced with nutritional abundance. The childhood obesity epidemic has been linked to a secular trend in advanced puberty in some populations. The increase in circulating leptin that occurs in association with obesity has been suggested to act as a signal that an adequate nutritional status exists for puberty to occur, allowing activation of central mechanisms. However, obesity-associated hyperleptinemia is linked to decreased leptin sensitivity, at least in adults. Here, we analyzed whether neonatal overnutrition modifies the response to an increase in leptin in peripubertal male rats, as previously demonstrated in females. Wistar rats were raised in litters of 4 (neonatal overnutrition) or 12 pups (controls) per dam. Leptin was administered sc (3 µg/g body weight) at postnatal day 35 and the rats killed 45 min or 2 h later. Postnatal overfeeding resulted in increased body weight and circulating leptin levels; however, we found no overweight-related changes in the mRNA levels of neuropeptides involved in metabolism or reproduction. In contrast, pituitary expression of luteinizing hormone (LH) beta-subunit was increased in overweight rats, as was testicular weight. There were no basal differences between L4 and L12 males or in their response to leptin administration in pSTAT3 levels in the hypothalamus at either 45 min or 2 h. In contrast, pJAK2 was found to be higher at 45 min in L4 compared to L12 males regardless of leptin treatment, while at 2 h it was higher in L4 leptin-treated males compared to L12 leptin-treated males, as well as L4 vehicle-treated rats. There were no changes in response to leptin administration in the expression of the neuropeptides analyzed. However, serum LH levels rose only in L4 males in response to leptin, but with no change in testosterone levels. In conclusion, the advancement in pubertal onset in males with neonatal overnutrition does not appear to be related to overt modifications in the central response to exogenous leptin during the peripubertal period.

Clinical profile of acne vulgaris in semiurban patients

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Acne is a chronic inflammatory disease of the pilosebaceous unit, mainly affecting face and frequently followed by scarring. It is the most common skin disease in an urban dermatology clinic in India. Adult acne is more common in women and may be a marker of hyperandrogenism.The present study was carried out to study the clinical profile of acne vulgaris in semiurban patients.</span></p><p class="abstract"><strong>Methods:</strong> <span lang="EN-IN">The study was conducted for 1 year on all eligible patients of acne vulgaris attending dermatology OPD of a hospital catering to semiurban patients. Data including grade of acne, markers of androgenicity and post-acne scarring was collected. Statistical analysis was done using SPSS 15 software</span>.<strong></strong></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">Frequency of acne vulgaris patients in the dermatology OPD was 2.8% with 429 acne patients out of 15,322 new patients. Female to male ratio was 1.44:1. The mean age of onset in males was 16.24 and in females, 14.84 years. Grade 2 acne (66%) was commonest followed by grade 3 (5.1%) and grade 4 (3.7%). Associated conditions seen were seborrhea (60.8%), alopecia (18.9%), acanthosis (4.9%) and PCOD (2.3%). Markers of androgenicity were more frequently seen in grade 2 acne which was statistically significant. Atrophic scars were commonest including icepick scars (80.2%), rolling scars (67.4%) and box scars (57.8%). </span></p><p class="abstract"><strong>Conclusions:</strong> <span lang="EN-IN">In our study females had an earlier onset and closed comedones were the most common acne lesion. Grade 2 acne vulgaris formed majority of patients. Grade 4 acne vulgaris was more common in males.</span></p>

Loss of PI3K p110α in the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice.

Deletion of PI3K catalytic subunit p110α in adipose tissue (aP2-Cre/p110αflx/flx, α−/− hereafter) results in increased adiposity, glucose intolerance, and liver steatosis. Because this endocrine organ releases hormones like leptin, which are important in reproductive physiology, we investigated the reproductive phenotype of α−/− males. Compared to controls, α−/− males displayed delayed onset of puberty accompanied by a reduction in plasma LH levels and testicular weight. At postnatal day 30, α−/− mice exhibited normal body weight but elevated fasted plasma leptin levels. Testicular leptin gene expression was increased, whereas expression of the cholesterol transporter StAR and of P450 cholesterol side chain cleavage enzyme was decreased. Adult α−/− males were infertile and exhibited hyperandrogenemia with normal basal LH, FSH, and estradiol levels. However, neither sperm counts nor sperm motility was different between genotypes. The mRNA levels of leptin and of 17-beta-dehydrogenase 3, and enzyme important for testosterone production, were significantly higher in the testis of adult α−/− males. The mRNA levels of ERα, an important regulator of intratesticular steroidogenesis, were lower in the testis of adult and peripubertal α−/− males. We propose that chronic hyperleptinemia contributes to the negative impact that disrupting PI3K signaling in adipocytes has on puberty onset, steroidogenesis, and fertility in males.

Perinatal triphenyl phosphate exposure accelerates type 2 diabetes onset and increases adipose accumulation in UCD-type 2 diabetes mellitus rats

Triphenyl phosphate (TPhP) is a flame retardant additive frequently found in consumer products and household dust. We administered 170μg of TPhP in maternal food from gestational day 8.5 to weaning and evaluated metabolic phenotypes of 3.5 month old male and female rats, and weight-matched males up to 6 months, to assess the development of obesity and type 2 diabetes mellitus (T2DM), respectively. Perinatal TPhP exposure increased body and fat mass in 3.5 month old male and female rats, while leptin and cumulative energy intake were elevated in males and females, respectively. Independent of body mass, perinatal TPhP exposure accelerated T2DM onset in males and increased plasma non-esterified- fasting fatty acids. These observations suggest that perinatal exposure to TPhP exacerbates the development of obesity in male and female UCDavis-T2DM rats and accelerates T2DM onset in male UCD-T2DM rats.

Interaction between neonatal maternal deprivation and serum leptin levels on metabolism, pubertal development, and sexual behavior in male and female rats.

BackgroundMaternal deprivation (MD) during neonatal life can have long-term effects on metabolism and behavior, with males and females responding differently. We previously reported that MD during 24 h at postnatal day (PND) 9 blocks the physiological neonatal leptin surge in both sexes. It is known that modifications in neonatal leptin levels can affect metabolism in adulthood. Thus, we hypothesized that at least some of the long-term metabolic changes that occur in response to MD are due to the decline in serum leptin during this critical period of development. Hence, we predicted that treatment with leptin during MD would normalize these metabolic changes, with this response also differing between the sexes.MethodsMD was carried-out in Wistar rats for 24 h on PND9. Control and MD rats of both sexes were treated from PND 9 to 13 with leptin (3 mg/kg/day sc) or vehicle. Weight gain, food intake, glucose tolerance, and pubertal onset were monitored. Sexual behavior was analyzed in males. Rats were killed at PND90, and serum hormones and hypothalamic neuropeptides involved in metabolic control and reproduction were measured. Results were analyzed by three-way analysis of covariance using sex, MD, and leptin treatment as factors and litter as the covariate and employing repeated measures where appropriate.ResultsIn males, MD advanced the external signs of puberty and increased serum insulin and triglyceride levels and hypothalamic proopiomelanocortin mRNA levels at PND90. Neonatal leptin treatment normalized these effects. In contrast, MD decreased circulating triglycerides, as well as estradiol levels, in females at PND90 and these changes were also normalized by neonatal leptin treatment. Neonatal leptin treatment also had long-term effects in control rats as it advanced the external signs of puberty in control males, but delayed them in females. Neonatal leptin treatment increased serum insulin and hypothalamic mRNA levels of the leptin receptor and cocaine- and amphetamine-regulated transcript in control males and increased orexin mRNA levels in controls of both sexes. Although pubertal onset in males was advanced by either MD or neonatal leptin treatment in males and delayed by leptin treatment in females, the mRNA levels of hypothalamic neuropeptides and receptors related to reproduction were not affected by MD or neonatal leptin treatment in either sex at PND90.ConclusionsThese findings indicate that some of the long-term changes in metabolic and reproductive parameters induced by MD, such as advanced pubertal onset and increased hypothalamic proopiomelanocortin (POMC) expression, hyperinsulinemia, and hypertriglyceridemia in adult males and decreased serum triglyceride and estradiol levels in females, are most likely due to the decrease in leptin levels during the period of MD.

Meta-analysis of sex differences in gene expression in schizophrenia.

Schizophrenia is a severe psychiatric disorder which influences around 1 % of the worldwide population. Differences between male and female patients with schizophrenia have been noted. There is an earlier age of onset in males compared with females with this diagnosis, and in addition, there are differences in symptom profiles between the sexes. The underlying molecular mechanism of sex difference remains unclear. Here we present a comprehensive analysis to reveal the sex differences in gene expression in schizophrenia with stringent statistics criteria. We compiled a data set consisting of 89 male controls, 90 male schizophrenia patients, 35 female controls and 32 female schizophrenia patients from six independent studies of the prefrontal cortex (PFC) in postmortem brain. When we tested for a sex by diagnosis interaction on gene expression, 23 genes were up-regulated and 23 genes were down-regulated in the male group (q-value < 0.05), several genes are related to energy metabolism, while 4 genes are located on sex chromosome. No genes were statistically significant in the female group when multiple testing correction were conducted (q-value <0.05), most likely due to the small sample size. Our protocol and results from the male group provide a starting point for identifying the underlying different mechanism between male and female schizophrenia patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0250-3) contains supplementary material, which is available to authorized users.

Incidence of diabetes mellitus type 2 complications among Saudi adult patients at primary health care center.

[Purpose] This study analyzed type 2 diabetes and its role in complications among adult Saudi patients. [Subjects] Patients attending four primary health care centers in Jeddah were enrolled. [Methods] A cross-sectional design study among Saudi patients attending Ministry of Health primary health care centers in Jeddah was selected for use by the Primary Health Care administration. Patients were interviewed with structured questionnaires to determine the presence of diabetes and risk factors using questions about the history of any disease. [Results] Diabetes mellitus was present in 234 subjects during the data collection period (March–June 2014). Mean patient age was 58 years; diabetes prevalence was 42% in males and 58% in females. The mean age for diabetes onset in males and females was 34 and 39 years, respectively. There was a higher incidence of obesity (75%) associated with a sedentary lifestyle (body mass index ≥25) in females (N= 96; 40%) compared with males (N= 87; 36%). In this study, >44% of individuals aged 55 or older had severe to uncontrolled diabetes with long-term complications. The age-adjusted incidence of hypertension and coronary heart disease was 38% and 24%, respectively, showing a clear incidence of diabetes associated with cardiovascular disease in Saudi Arabia. [Conclusion] This study found that a multifactorial approach to managing diabetes complication risks is needed.

X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care

To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked "deafness" genes (DFNX). Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus POU3F4. The family pedigrees reveal characteristic X-linked inheritance patterns. Phenotypic features associated with the SMPX (DFNX4) mutation include early onset in males with rapid progression from mild and flat to sloping sensorineural loss, with highly variable onset and hearing loss severity in females. In contrast, phenotypic features associated with the POU3F4 (DFNX2) mutation are characterized by an early onset, mixed hearing loss with fluctuation in males, and a normal hearing phenotype reported for females. The study shows how this unique inheritance pattern and both gender and mutation-specific phenotype variations can alert audiologists to the presence of X-linked genetic etiologies in their clinical practice. By incorporating this knowledge into clinical decision making, audiologists can facilitate the early identification of X-linked hearing loss and contribute to the effective team management of affected families.

Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty.

Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10(-9)), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10(-5)) and short adult stature (p = 7.5 × 10(-6)) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.

Analysis of Gender Differences in Genetic Risk: Association of TNFAIP3 Polymorphism with Male Childhood-Onset Systemic Lupus Erythematosus in the Japanese Population

BackgroundSystemic lupus erythematosus (SLE) is a systemic multisystem autoimmune disorder influenced by genetic background and environmental factors. Our aim here was to replicate findings of associations between 7 of the implicated single nucleotide polymorphisms (SNPs) in IRF5, BLK, STAT4, TNFAIP3, SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the Japanese population. In particular, we focused on gender differences in allelic frequencies.Methodology/Principal FindingsThe 7 SNPs were genotyped using TaqMan assays in 75 patients with childhood-onset SLE and in 190 healthy controls. The relationship between the cumulative number of risk alleles and SLE manifestations was explored in childhood-onset SLE. Logistic regression was used to test the effect of each polymorphism on susceptibility to SLE, and Wilcoxon rank sum testing was used for comparison of total risk alleles. Data on rs7574865 in the STAT4 gene and rs9138 in SPP1 were replicated for associations with SLE when comparing cases and controls (corrected P values ranging from 0.0043 to 0.027). The rs2230926 allele of TNFAIP3 was associated with susceptibility to SLE in males, but after Bonferroni correction there were no significant associations with any of the other four SNPs in IRF5, BLK, TNIP1 and ETS1 genes. The cumulative number of risk alleles was significantly increased in childhood-onset SLE relative to healthy controls (P = 0.0000041). Male SLE patients had a slightly but significantly higher frequency of the TNFAIP3 (rs2230926G) risk allele than female patients (odds ratio [OR] = 4.05, 95% confidence interval [95%CI] = 1.46–11.2 P<0.05).ConclusionsAssociations of polymorphisms in STAT4 and SPP1 with childhood-onset SLE were confirmed in a Japanese population. Although these are preliminary results for a limited number of cases, TNFAIP3 rs2230926G may be an important predictor of disease onset in males. We also replicated findings that the cumulative number of risk alleles was significantly increased in childhood-onset SLE.

Comprehensive Assessment of a Chlorinated Drinking Water Concentrate in a Rat Multigenerational Reproductive Toxicity Study

Some epidemiological studies report associations between drinking water disinfection byproducts (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136-fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological end points, and most neurobehavioral end points. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research, while the largely negative findings, particularly for pup weight and prenatal loss, are notable.

Clinical study on psoriasis patients for past 30 years (1982–2012) in Seoul National University Hospital Psoriasis Clinic

Psoriasis is a chronic relapsing disorder which shows variable clinical features. The long-term clinical study with many patients is important to elucidate the epidemiologic characteristics and clinical features of psoriasis. The purpose of this study was to analyze the epidemiologic characteristics and clinical features of psoriasis in Korean patients. Epidemiologic and clinic data and assessments for severity of extent and activity of psoriasis were collected from the medical records of 5084 patients, who had been newly diagnosed with psoriasis in the Psoriasis Clinic of Seoul National University Hospital between 1982 and 2012. The sex ratio of the psoriasis patients was 1.2:1 (male 54.6%, female 45.4%). The peak age of onset in males was 20s, while it was the teenage years in females. A total of 63.5% of patients developed psoriasis before 30years of age. Family history of psoriasis was observed in 26.0% of patients. Moderate to severe extent of involvement were more frequently observed in male patients and patients under 30years of onset age than in females and patients 30years or over of onset age, respectively. Moderate to severe disease activity were also more frequently presented in male patients, but not in patients under 30years of onset age. The most common morphological type was nummular (56.7%), followed by large plaque (28.5%) and guttate (8.5%). Nail involvement accompanied in 26.4% of patients. We demonstrated the epidemiologic and clinical characteristics of psoriasis in Korean patients.

Amyotrophic lateral sclerosis: A hormonal condition?

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disorder in adults. This fatal condition, due to degeneration of upper and lower motor neurons in spinal and bulbar myotomes, leads to death from respiratory failure after median disease duration of 36 months. ALS is sporadic in more than 90% of cases and familial in the remaining cases. Most studies show male predominance with a gender ratio of 3:2, but gender differences are age related. The phenotype of ALS is also different in males and females with a predominance of limb onset in males and bulbar onset in females. While age and site of onset impact survival rate, and are both related to gender, gender by itself has not clearly been shown to have an effect on survival. Given this complex relationship between gender and ALS, we developed a hypothesis about hormone involvement in ALS aetiology by suggesting protective effect of oestrogens and adverse effect of androgens.

Gender difference in age at onset of schizophrenia: a meta-analysis

Most studies reporting the gender difference in age at onset of schizophrenia show an earlier onset in males, but vary considerably in their estimates of the difference. This may be due to variations in study design, setting and diagnostic criteria. In particular, several studies conducted in developing countries have found no difference or a reversed effect whereby females have an earlier onset. The aim of the study was to investigate gender differences in age of onset, and the impact of study design and setting on estimates thereof. Study methods were a systematic literature search, meta-analysis and meta-regression. A total of 46 studies with 29,218 males and 19,402 females fulfilled the inclusion criteria and were entered into a meta-analysis. A random-effects model gave a pooled estimate of the gender difference of 1.07 years (95% confidence interval 0.21-1.93) for age at first admission of schizophrenia, with males having earlier onset. The gender difference in age at onset was not significantly different between developed and developing countries. Studies using diagnostic and statistical manual of mental disorders (DSM) criteria showed a significantly greater gender difference in age at onset than studies using International Classification Of Diseases (ICD) criteria, the latter showing no difference. The gender difference in age of onset in schizophrenia is smaller than previously thought, and appears absent in studies using ICD. There is no evidence that the gender difference differs between developed and developing countries.

Neonatal lipopolysaccharide exposure impairs sexual development and reproductive success in the Wistar rat

We investigated, in rats, whether neonatal exposure to bacterial lipopolysaccharide (LPS) impairs sexual development, sexual decline, and reproductive behaviour in later life. Rats were administered either LPS (Salmonella enterica, serotype enteritidis, 0.05mg/kg, ip) or saline (equivolume) on days 3 and 5 postpartum. The immediate and long-term effect of treatment on HPA and HPG hormones, testicular morphology, and mating behaviour was assessed. Neonatal LPS exposure induced a significant increase in corticosterone compared to controls, as well as reduced testosterone and LH in males and LH in females immediately following neonatal drug exposure. Neonatal LPS exposure disrupted the normal weight-to-age ratio of puberty onset in males and females, and impaired sexual performance in adulthood. Reproductive function was reflected in significantly diminished sperm presence in rats that had received neonatal LPS. LPS-treated females exhibited LH suppression during puberty, and males demonstrated testosterone suppression in late adulthood. Testosterone and LH surges during mating were significantly reduced in adult offspring treated with LPS as neonates. Furthermore, animals exposed to neonatal LPS and subsequent stress in adulthood, exhibited significantly blunted corticosterone responses. Morphometric assessment of testes taken from neonates revealed reduced gonocyte genesis immediately following LPS exposure and increased seminiferous disorganisation of the epithelium in these animals in adulthood. This research demonstrates the long-term impact of neonatal bacterial exposure on reproductive success given that early life exposure to bacteria disrupted puberty onset and sexual performance. Associated changes in neuroendocrine functioning suggest a possible mechanism through which a subfertile phenotype may arise.

Effects of gender in amyotrophic lateral sclerosis

There is evidence that amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is more common in men than in women and that gender influences the clinical features of the disease. The causes of this are unknown. This review examines the gender differences that are found in ALS and postulates reasons for these differences. A literature review of PubMed (with no date limits) was performed to find information about gender differences in the incidence, prevalence, and clinical features of ALS, using the search terms ALS or MND and gender or sex, ALS prevalence, and SOD1 mice and gender. Articles were reviewed for information about gender differences, together with other articles that were already known to the authors. The incidence and prevalence of ALS are greater in men than in women. This gender difference is seen in large studies that included all ALS patients (sporadic and familial), but is not seen when familial ALS is studied independently. Men predominate in the younger age groups of patients with ALS. Sporadic ALS has different clinical features in men and women, with men having a greater likelihood of onset in the spinal regions, and women tending to have onset in the bulbar region. Gender appears to have no clear effect on survival. In animals with superoxide dismutase 1 (sod1) mutations, sex does affect the clinical course of disease, with earlier onset in males. Possible reasons for the differences in ALS between men and women include different exposures to environmental toxins, different biological responses to exogenous toxins, and possibly underlying differences between the male and female nervous systems and different abilities to repair damage. There is a complex interaction between gender and clinical phenotypes in ALS. Understanding the causes of the gender differences could give clues to processes that modify the disease.