Sex Specificity Research Articles

Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms.

Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.

Does Hyperoxia Alter the Mechanoreflex in Young Healthy Males and Females?

Passive limb movement (PLM) has been used as a method of activating the mechanoreflex, inducing limb hyperemia which is nitric oxide (NO) dependent. Breathing hyperoxic gas has been used as a model to elevate free radicals (FR), though it remains to be seen, in humans, if acute elevations in FR alter the mechanoreflex response to PLM, and whether the effect may be sex specific. PURPOSE: The purpose of this study was to compare the male and female central and peripheral hemodynamic responses to dynamic PLM, under normoxic (21% O2) and hyperoxic (100% O2) conditions. METHODS: In 23 young healthy participants (12 female(F) and 11 male(M)) using a single blind design, participants were positioned supine and breathed normoxic (21% O2) and hyperoxic (100% O2) gas from a Douglas bag for 10 minutes, after which 2 minutes of PLM were performed. Central hemodynamic responses (cardiac output [CO], stroke volume [SV], and HR), were measured using a Finometer, while a near-infrared spectrometer (NIRS) was used to assess the microvascular response (tissue oxygen saturation, StO2%) at baseline and during the PLM. RESULTS: No sex differences in hemodynamics were observed at baseline in normoxia (p>0.05). In response to PLM, both sexes increased HR and CO from baseline (p<0.05); however, males elicited significantly higher CO response than females (ΔCO: 1.7±0.7 vs. 0.9±0.6 L/min, p<0.05). Peripherally, PLM increased StO2 from baseline for both sexes (p<0.05), though there was a significant difference in the peripheral response to PLM between the sexes (M: 4.2±2.0 vs F: 2.3±2.7 ΔStO2%, p<0.05). Hyperoxia had no effect on baseline CO or StO2 (p>0.05) or the response to PLM, and the sex difference persisted (ΔCO: 1.8 ± 1.0 vs 1.1 ± 0.6 L/min, M v. F) (p<0.05). PLM induced significant changes in StO2, which were not different from normoxia, though the sex specificity persisted (M: 4.5±1.8 vs F: 2.1±2.7 ΔStO2%, p<0.05). CONCLUSION: The present study provides further evidence that females exhibit an attenuated mechanoreflex as compared to males, which may reduce CVD risk. Though, unlike the macrovascular responses to PLM which have been reported to be similar between sexes, the microvascular responses to PLM may differ. In the current model, prior inhalation of 100% oxygen had no effect on the mechanoreflex in in young healthy males and females.

Sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats

Although cardiotoxicity has been recognized as one of the adverse effects of the immunosuppressant drug cyclosporine A (CSA), limited or no information is available regarding the sex specificity of CSA cardiotoxicity. Here we tested the hypothesis that the left ventricular (LV) and electrocardiographic effects of chronic CSA and related inflammatory and histopathological derangements are sex‐related. Adult male and female rats were treated with CSA (15 mg/kg/day, sc) or its vehicle for three weeks. Afterwards, studies were undertaken to assess: (i) LV and electrocardiographic characteristics, and (ii) alterations in LV inflammatory (nuclear factor kappa B, NFκB; angiotensin receptors type 1, AT1) and histopathological profiles. In both male and female rats, CSA significantly reduced LV slope of end‐systolic pressure volume relationship (ESPVR), and isovolumic relaxation constant (Tau), suggesting LV systolic and diastolic dysfunction. Histopathologically, the treatment of either rat sex with CSA resulted in vascular congestion, blood extravasation, and pyknotic or even absent nuclei. We also report sex‐dependent electrocardiographic effects for CSA. Whereas CSA increased QTc and T peak trend intervals in male rats, markers of LV arrhythmogenesis, evidence of prolonged AV conduction was noted in female rats as reflected by the prolonged P duration and PR interval. Other sex‐related effects for CSA included (i) increased blood cholesterol, rate of rise (dp/dtmax) and fall (dp/dtmin) in LV pressure and LV content of NFκB and AT1 expression in male rats, and (ii) increased LV content of adiponectin and elevated systolic and diastolic blood pressures in female rats. Although the two rat sexes are prone to the negative LV influences of CSA, the male rat seems to be more vulnerable to inflammatory and LV adverse effects of CSA.Support or Funding InformationThis work was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant No. (166 ‐ 1001 ‐D1435). The authors, therefore, acknowledge with thanks DSR technical and financial support

Gender features of self-description of schoolchildren’s physical condition

Purpose: to study age and gender features of schoolchildren’s attitude to their physical “self”. Material: in the research pupils of 5-11 forms (n=365) participated. They were: 177 boys and 188 girls. Individual profile of personality’s physical “self” was studied. For this purpose test-questionnaire was used and self description of physical condition. Results: it was found that self assessment of schoolchildren’s physical condition was too high. It was in average 80-85% from maximal indicator. It was also found that by all indicators sportsmen had higher self-esteem. For development of boys and girls’ individual abilities and bents, overcoming of gender-role stereotypes it is necessary to have knowledge about sex and gender specificities of schoolchildren’s physical development as well as about their influence on self esteem and formation of physical qualities. Conclusions: we showed that it was possible to correct physical education curriculum and its implementation in educational process.

Sex Specification and Heterogeneity of Primordial Germ Cells in Mice

In mice, primordial germ cells migrate into the genital ridges by embryonic day 13.5 (E13.5), where they are then subjected to a sex-specific fate with female and male primordial germ cells undergoing mitotic arrest and meiosis, respectively. However, the sex-specific basis of primordial germ cell differentiation is poorly understood. The aim of this study was to investigate the sex-specific features of mouse primordial germ cells. We performed RNA-sequencing (seq) of E13.5 female and male mouse primordial germ cells using next-generation sequencing. We identified 651 and 428 differentially expressed transcripts (>2-fold, P < 0.05) in female and male primordial germ cells, respectively. Of these, many transcription factors were identified. Gene ontology and network analysis revealed differing functions of the identified female- and male-specific genes that were associated with primordial germ cell acquisition of sex-specific properties required for differentiation into germ cells. Furthermore, DNA methylation and ChIP-seq analysis of histone modifications showed that hypomethylated gene promoter regions were bound with H3K4me3 and H3K27me3. Our global transcriptome data showed that in mice, primordial germ cells are decisively assigned to a sex-specific differentiation program by E13.5, which is necessary for the development of vital germ cells.

Sociodemographic and psychiatric diagnostic predictors of 3-year incidence of DSM-IV substance use disorders among men and women in the National Epidemiologic Survey on Alcohol and Related Conditions.

Incidence rates of alcohol and drug use disorders (AUDs and DUDs) are consistently higher in men than women, but information on whether sociodemographic and psychiatric diagnostic predictors of AUD and DUD incidence differ by sex is limited. Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, sex-specific 3-year incidence rates of AUDs and DUDs among United States adults were compared by sociodemographic variables and baseline psychiatric disorders. Sex-specific logistic regression models estimated odds ratios for prediction of incident AUDs and DUDs, adjusting for potentially confounding baseline sociodemographic and diagnostic variables. Few statistically significant sex differences in predictive relationships were identified and those observed were generally modest. Prospective research is needed to identify predictors of incident DSM-5 AUDs and DUDs and their underlying mechanisms, including whether there is sex specificity by developmental phase, in the role of additional comorbidity in etiology and course, and in outcomes of prevention and treatment.

In Vitro and In Vivo Modeling of Spinal and Bulbar Muscular Atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease characterized by late-onset, progressive degeneration of lower motor neurons and skeletal muscle atrophy. SBMA is caused by expansions of a CAG trinucleotide repeat in the gene encoding the androgen receptor (AR). One striking feature of SBMA is sex specificity: SBMA fully manifests only in males, whereas females show subclinical or mild disease manifestations even when homozygous for the mutation. Since the identification of the mutation responsible for SBMA in 1991, several cell and animal models have been developed to recapitulate the main features of disease in vitro and in vivo. In this review, we describe the most widely used cellular and animal models of SBMA, highlighting advantages and disadvantages in the use of these models to gain mechanistic and therapeutic insights into SBMA.

Abstract 12621: Gender Differences Among Implantable Cardioverter Defibrillators Recipients in the Setting of Primary Prevention

Background: Data regarding sex specificities in the use, benefits and complications of implantable cardioverter-defibrillators (ICDs) in primary prevention in the real-world European setting are sparse. Methods: Using a large multicentric cohort of consecutive patients referred for ICD implantation for primary prevention (2002-2012), in the setting of coronary artery disease or dilated cardiomyopathy, we examined potential sex differences in subjects’ characteristics and outcomes. Results: Of 5,539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy (CRT-D). Compared to men, women presented a significantly higher proportion of dilated cardiomyopathy (60.2% vs. 36.2%, P120ms: 74.6% vs. 68.5%, P=0.003), higher New York Heart Association functional class (2.5±0.7 vs. 2.4±0.7, P=0.003) and lower prevalence of atrial fibrillation (18.7% vs. 24.9%, P&lt;0.001). During a 16,786 patient-years follow-up, overall, fewer appropriate therapies were observed in women (HR = 0.59, CI95% 0.45-0.76; P&lt;0.001). By contrast, no sex-specific interaction was observed for inappropriate shocks (OR for women = 1.00, 95%CI 0.74-1.35, P=0.997) and mortality (HR = 0.87; 95%CI 0.66-1.15, P=0.324), with similar patterns of cause of deaths. Conclusion: In our real life registry, women account for the minority of ICD recipients. While female ICD recipients present with features of more severe heart failure in the setting of primary prevention of sudden cardiac death, we observed they have a 40% lower incidence of appropriate therapies.

Current Clinical Features of New Patients With Takayasu Arteritis Observed From Cross-Country Research in Japan: Age and Sex Specificity.

The clinical features of newly diagnosed Japanese patients with Takayasu arteritis and its age or sex specificities are unknown. We analyzed information from nationwide registration forms submitted by patients with Takayasu arteritis between April 2001 and March 2011 as part of a research program by the Japanese Ministry of Health, Labor and Welfare. Among the 7779 patients who submitted their forms, 1372 newly registered patients with Takayasu arteritis were enrolled; 83.8% were female. The median age at onset was 35 years, which was significantly higher in male patients (median, 43.5 years) than in female patients (median, 34 years; P<0.001). Local symptoms and findings were most commonly observed in the cervicobrachial area, with more complaints in the head or neck than in the upper limbs. Approximately 85% of the patients had vascular involvements in the aortic arch or its major branches; many young female patients had localized lesions. Although male patients had extensive aortic lesions or aneurysms with more complications, localized abdominal lesions were relatively more frequent in male patients with age at onset >40 years than in other age-sex groups. Disease statuses were severe in patients who registered at ≥1 year after onset. The proportions of male patients and patients with elderly onset increased in newly diagnosed patients with Takayasu arteritis. Their clinical and angiographic features differed according to onset age and sex.

Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels.

Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. High PCB levels were associated with an increase of SHBG (P-trend < 0.01) and AMH (P-trend < 0.05) and a decrease of fT (P-trend < 0.05) and AI (P-trend < 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P < 0.05) and E2 (P < 0.01) and a decrease of fT (P < 0.05) and AI (P < 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare.

Sex-specific cardiac cardiolipin remodelling after doxorubicin treatment.

BackgroundImbalance in lipid metabolism and membrane lipid homeostasis has been observed in numerous diseases including heart failure and cardiotoxicity. Growing evidence links phospholipid alterations especially cardiolipins (CLs) to defects in mitochondrial function and energy metabolism in heart failure. We have shown recently that doxorubicin cardiotoxicity is more severe in male than female Wistar rats. We aimed to study whether this sex specificity is linked to differences in cardiac phospholipid profiles.ResultsAdult male and female rats were injected 2 mg/kg doxorubicin weekly for 7 weeks. Cardiac phospholipid molecular species were determined by liquid chromatography coupled with mass spectrometry fragmentation (LC)/MSn. Sex difference in phosphatidylethanolamine and phosphatidylcholine species containing docosahexaenoic and docosapentaenoic acyl chains was observed, females having more than males. In both sexes, doxorubicin induced an important loss of the main CL(18:2)4, while the level of monolysocardiolipin MLCL(18:2)3 remained stable. However, a severe remodelling appeared in treated rats with the longest CL acyl chains in doxorubicin-treated females, which might compensate for the loss of tetra-linoleoyl CL. The level of oxidized cardiolipin was not particularly increased after doxorubicin treatment. Finally, expression of genes involved in the biosynthesis of fatty acid appeared to be decreased in doxorubicin-treated males.ConclusionsThese results emphasize for the first time the cardiac remodelling in the phospholipid classes after doxorubicin treatment. These observations suggest that doxorubicin has a sex-specific impact on the heart phospholipidome especially on cardiolipin, an essential mitochondrial lipid. Further studies are needed to better understand the roles of lipids in the anthracycline cardiotoxicity and sex differences, but phospholipid cardioprotection seems a valuable new additive therapeutic strategy for anthracycline cardiotoxicity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-015-0039-5) contains supplementary material, which is available to authorized users.

Context dependence of maternal effects: testing assumptions of optimal egg size, differential, and sex allocation models.

If offspring develop in adverse conditions, the maternal component of their phenotypic variation might increase due to the stronger dependence of offspring traits on parental investment. This should result in increased parental investment to individual offspring, as assumed by the model of optimal egg size. The opposite pattern, i.e., stronger dependence of offspring fitness on parental investment and consequently larger parental investment under good conditions is assumed by both the theory of differential allocation if attractive males provide material benefits, and reproductive compensation if they invest less into paternal care. Another influential idea is the Trivers-Willard model, which assumes sex-specific dependence of offspring fitness on parental investment. Here we tested these ideas by examining the effects of egg size on offspring fitness across many postnatal contexts in the Collared Flycatcher Ficedula albicollis. We employed a cross-fostering design that generated variation in egg size within nests and used brood means of fledgling mass as a functional measure of the quality of rearing conditions. Effects of egg size on three offspring traits, including lifetime reproductive success of recruits, were more pronounced in low-quality broods. These results support the assumption of the model of optimal egg size. Based on female preference for males providing material benefits, this pattern could support differential allocation, if attractive males invest less in paternal care, or reproductive compensation, if they invest more. By comparison, we did not find any evidence for sex specificity of fitness returns that might explain sex monomorphism of egg size in this species. The challenge for future studies will be the integration of components of parental investment and offspring fitness into their global measures and testing how the former affects the latter across gradients of postnatal conditions.

The placental sulfate transporter, Slc13a4, is critical for skeletal development in mice.

The placental sulfate transporter, Slc13a4, is critical for skeletal development in mice.

Integrative analysis of methylome and transcriptome in human blood identifies extensive sex- and immune cell-specific differentially methylated regions

The relationship between DNA methylation and gene expression is complex and elusive. To further elucidate these relations, we performed an integrative analysis of the methylome and transcriptome of 4 circulating immune cell subsets (B cells, monocytes, CD4+, and CD8+ T cells) from healthy females. Additionally, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male data sets. Immune cell-specific differentially methylated regions (DMRs) were found to be highly similar between sexes, with an average correlation coefficient of 0.82; however, numerous sex-specific DMRs, shared by the cell subsets, were identified, mainly on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in disorders with sexual dimorphism, such as autoimmune diseases. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, indicating that distal regulatory elements are important in immune cell specificity. In contrast, sex-specific DMRs were overrepresented in CpG islands, suggesting that the epigenetic regulatory mechanisms of sex and immune cell specificity may differ. Both positive and, more frequently, negative correlations between subset-specific expression and methylation were observed, and cell-specific DMRs of both interactions were associated with similar biological pathways, while sex-specific DMRs were linked to networks of early development or estrogen receptor and immune-related molecules. Our findings of immune cell- and sex-specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions and may particularly contribute to research of immune-mediated diseases.

Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children: Tracing the complexity of human postnatal steroidogenesis

ContextComplex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3–6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. ObjectiveThe aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. MethodsWe conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC–MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. Results61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. ConclusionThe urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

Tissue and sex specificities in Ca2+ handling by isolated mitochondria in conditions avoiding the permeability transition.

What is the central question of this study? The assessment of Ca(2+) handling by isolated mitochondria can be biased by dysfunctions secondary to Ca(2+) -induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca(2+) transport are still unsettled questions. What is the main finding and its importance? If MPT is not prevented during Ca(2+) transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca(2+) handling, particularly in the Ca(2+) efflux pathways. The characteristics of mitochondria, including their Ca(2+) transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca(2+) handling by isolated mitochondria may be biased by dysfunction secondary to Ca(2+) -induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca(2+) transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca(2+) and the rates of mitochondrial Ca(2+) efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca(2+) transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca(2+), Mg(2+) and Na(+). The Ca(2+) influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca(2+) efflux rates exhibited more tissue diversity, especially in the presence of Na(+). Interestingly, the Na(+)-independent Ca(2+) efflux was highest in the heart mitochondria (∼ 4 nmol mg(-1) min(-1)), thus challenging the view that cardiac mitochondrial Ca(2+) efflux relies almost exclusively on a Na(+)-dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca(2+) homeostasis and in the ADP-stimulated respiration of liver mitochondria (∼ 20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca(2+) handling by isolated mitochondria.

B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in humanized mice

Rheumatoid arthritis (RA) occurs two times more often in women than men. B cell depletion has been shown to be efficacious in treating RA. Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice. Here we evaluated the mechanism of efficacy of the B cell depletion in treating arthritis-susceptible DQ8 mice. The data show that arthritic DQ8 mice treated with anti-CD20 antibody in therapeutic protocols show milder disease severity in females as compared to males, which is associated with decreased antibodies to citrullinated proteins and reduced levels of IL-23 and CCL5. Treatment led to significantly increased numbers of T regulatory and monocyte-derived suppressor F4/80+Gr1hi cells in females as compared to male DQ8 mice. Our observations suggest that therapeutic strategies that target B cells may benefit females while functions of DCs might be relatively more important for men than women.

Stem Cell Aging and Sex: Are We Missing Something?

Longevity differs between sexes, with females being longer-lived in most mammals, including humans. One hallmark of aging is the functional decline of stem cells. Thus, a key question is whether the aging of stem cells differs between males and females and whether this has consequences for disease and lifespan.

Parathyroid Hormone is Related to Dysplasia and a Higher Rate of Distal Colorectal Adenoma in Women but Not Men.

Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5%) of the distal colon compared to women below the cut-off (91/659; 13.8%; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study.

ACTUAL WAYS FOR OVERCOMING THE FACTORS ADVERSELY AFFECTING THE CHILDREN AND ADOLESCENTS’ HEALTH IN EDUCATIONAL INSTITUTIONS

The paper analyzes a widely discussed problem of the negative health dynamics of the growing generation, and points out the necessity of complex consideration of all the factors adversely affecting children’s health. The special emphasis is on the fallowing harmful factors: intensification of training process; discrepancy between the applied training methods and techniques on the one side, and children’s age, sex and functional specifics and capabilities on the other side; shortcomings in organizing children’s physical activities; limitations of the expositive illustrative methods for developing the healthy lifestyle habits. The other group of factors is related to the teaching style and professional characteristics of the teachers. They include the common practice of «stress» tactics; incompetence in health saving technologies; personal indisposition and psychological drawbacks. The situation is exacerbated by the absence of psychologists and pediatricians in educational institutions. The multilevel approach to solving the problems of students’ health preservation and promotion involves the elicitation of objective, subjective, inschool and out-of-school health determining factors. The paper denotes the actual ways of children’s health preservation at the level of related ministries, departments, and educational institutions.