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Journal of Pediatric Urology Feb 2021Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment team as some of these children develop gender identity disorder (GID) when they become adults. In this systematic review and meta-analysis we have analyzed the prevalence of GID in adolescent and adults with DSD. The secondary outcome of this review is to help physicians in appropriate sex assignment of DSD children so that development of GID in later life can be reduced.
METHODS
Pubmed/Index medicus were searched for "intersex" [All fields] OR "disorders of sexual differentiation AND "gender identity disorder OR gender dysphoria" [MeSH] for articles published between 2005 and 2020. Typical diagnoses included were congenital adrenal hyperplasia (CAH); complete androgen insensitivity syndrome (CAIS); partial androgen insensitivity syndrome (PAIS); 5 alpha reductase deficiency (5ARD); 17-hydroxysteroid dehydrogenase deficiency (17HSD); mixed gonadal dysgenesis (MGD) and complete gonadal dysgenesis (CGD). GID or gender dysphoria (a strong feeling of dissatisfaction about oneself as male or female) prevalence in DSD patients older than 12 years of age was extracted. Within each condition, GID percentage was compared between female and male rearing.
RESULTS
The I2statistics for prevalence of GID in DSD showed high heterogeneity with I2 of 93% (95% C.I 90-95%) among the 20 articles included. The overall prevalence of GID among those with DSD was 15% (95% C.I 13-17%). CAH reared females had 4% GID while CAH reared males had significantly higher GID at 15% (p = 0.0056). All CAIS patients were raised as females and the prevalence of GID was 1.7%. GID prevalence was 12% in PAIS raised as females while 25% in those raised as males with no significant difference (p = 0.134). GID was significantly high in 5ARD (53%) and 17HSD (53%) reared as females with half of them virilizing at puberty forcing a gender change. Among sex chromosome DSD 22% of those reared as females had GID while none in those raised as male with no significant difference.
CONCLUSIONS
GID is low in women with CAH, CAIS and CGD favoring female sex of rearing in these conditions. GID is high in women with 5ARD/17HSD favoring male sex of rearing in these conditions. GID is variable in PAIS or MGD and no recommendations on sex of rearing could be made in these conditions. Each DSD patient is unique and they warrant multi-disciplinary care and long term psycho sexual support.
Topics: Adolescent; Adult; Child; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Gender Dysphoria; Gender Identity; Humans; Male; Sexual Development; Steroid Metabolism, Inborn Errors
PubMed: 33246831
DOI: 10.1016/j.jpurol.2020.11.017 -
BioMed Research International 2014Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the... (Review)
Review
Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women.
Topics: Adipokines; Central Nervous System; Estradiol; Estrogens; Female; Humans; Lipid Metabolism; Menopause; Middle Aged; Obesity; Overweight; Receptors, Estrogen
PubMed: 24734243
DOI: 10.1155/2014/757461 -
Journal of Neuroinflammation Jun 2015Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated... (Review)
Review
BACKGROUND
Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain.
METHODS
We searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions.
RESULTS
Fifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels.
INTERPRETATION
Animal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.
Topics: Animals; Delirium; Disease Models, Animal; Escherichia coli; Female; Inflammation; Lipopolysaccharides; Male; Mice; Microglia; Rats; Sepsis
PubMed: 26048578
DOI: 10.1186/s12974-015-0332-6 -
Ecotoxicology and Environmental Safety Nov 2023Human activities have been exerting widespread stress and environmental risks in aquatic ecosystems. Environmental stress, including temperature rise, acidification,... (Review)
Review
Human activities have been exerting widespread stress and environmental risks in aquatic ecosystems. Environmental stress, including temperature rise, acidification, hypoxia, light pollution, and crowding, had a considerable negative impact on the life histology of aquatic animals, especially on sex differentiation (SDi) and the resulting sex ratios. Understanding how the sex of fish responds to stressful environments is of great importance for understanding the origin and maintenance of sex, the dynamics of the natural population in the changing world, and the precise application of sex control in aquaculture. This review conducted an exhaustive search of the available literature on the influence of environmental stress (ES) on SDi. Evidence has shown that all types of ES can affect SDi and universally result in an increase in males or masculinization, which has been reported in 100 fish species and 121 cases. Then, this comprehensive review aimed to summarize the molecular biology, physiology, cytology, and epigenetic mechanisms through which ES contributes to male development or masculinization. The relationship between ES and fish SDi from multiple aspects was analyzed, and it was found that environmental sex differentiation (ESDi) is the result of the combined effects of genetic and epigenetic factors, self-physiological regulation, and response to environmental signals, which involves a sophisticated network of various hormones and numerous genes at multiple levels and multiple gradations in bipotential gonads. In both normal male differentiation and ES-induced masculinization, the stress pathway and epigenetic regulation play important roles; however, how they co-regulate SDi is unclear. Evidence suggests that the universal emergence or increase in males in aquatic animals is an adaptation to moderate ES. ES-induced sex reversal should be fully investigated in more fish species and extensively in the wild. The potential aquaculture applications and difficulties associated with ESDi have also been addressed. Finally, the knowledge gaps in the ESDi are presented, which will guide the priorities of future research.
Topics: Animals; Humans; Male; Ecosystem; Epigenesis, Genetic; Sex Differentiation; Aquaculture; Gonads
PubMed: 37918334
DOI: 10.1016/j.ecoenv.2023.115654 -
JAMA Neurology Sep 2019Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate...
IMPORTANCE
Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.
OBJECTIVES
To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.
DATA SOURCES
PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.
STUDY SELECTION
Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.
DATA EXTRACTION AND SYNTHESIS
Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.
MAIN OUTCOME AND MEASURE
The cNfL levels adjusted for age and sex across diagnoses.
RESULTS
Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.
CONCLUSIONS AND RELEVANCE
These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
PubMed: 31206160
DOI: 10.1001/jamaneurol.2019.1534 -
Biology of Sex Differences Jun 2022In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying... (Review)
Review
In this systematic review, we highlight the differences between the male and female zebrafish brains to understand their differentiation and their use in studying sex-specific neurological diseases. Male and female brains display subtle differences at the cellular level which may be important in driving sex-specific signaling. Sex differences in the brain have been observed in humans as well as in non-human species. However, the molecular mechanisms of brain sex differentiation remain unclear. The classical model of brain sex differentiation suggests that the steroid hormones derived from the gonads are the primary determinants in establishing male and female neural networks. Recent studies indicate that the developing brain shows sex-specific differences in gene expression prior to gonadal hormone action. Hence, genetic differences may also be responsible for differentiating the brain into male and female types. Understanding the signaling mechanisms involved in brain sex differentiation could help further elucidate the sex-specific incidences of certain neurological diseases. The zebrafish model could be appropriate for enhancing our understanding of brain sex differentiation and the signaling involved in neurological diseases. Zebrafish brains show sex-specific differences at the hormonal level, and recent advances in RNA sequencing have highlighted critical sex-specific differences at the transcript level. The differences are also evident at the cellular and metabolite levels, which could be important in organizing sex-specific neuronal signaling. Furthermore, in addition to having one ortholog for 70% of the human gene, zebrafish also shares brain structural similarities with other higher eukaryotes, including mammals. Hence, deciphering brain sex differentiation in zebrafish will help further enhance the diagnostic and pharmacological intervention of neurological diseases.
Topics: Animals; Brain; Female; Gonads; Male; Mammals; Sex Characteristics; Sex Differentiation; Zebrafish
PubMed: 35715828
DOI: 10.1186/s13293-022-00442-2 -
International Journal of Environmental... Sep 2021Previous studies have demonstrated cardiovascular health effects of environmental noise exposure, partly showing different effect estimates for males and females. This... (Review)
Review
Previous studies have demonstrated cardiovascular health effects of environmental noise exposure, partly showing different effect estimates for males and females. This cannot be explained by biological differences between males and females alone. It is assumed that health outcomes and exposure patterns also depend on gender, determined by social, economic, and cultural factors in society. This systematic review evaluated the current state of how sex/gender is integrated in studies on environmental noise associated with hypertension, blood pressure, and ischemic heart diseases. A systematic literature search was conducted in three different databases, identifying thirty studies published between 1 January 2000 and 2 February 2020. Effects varied, with no consistent findings for both males and females. All studies used a binary operationalization of sex/gender, assuming static differences between males and females. The differentiation between biological and social dimensions of sex/gender was not present in any of the studies and the terms "sex" and "gender" were used interchangeably. However, biological and social dimensions of sex/gender were unconsciously taken up in the discussion of the results. Integrating sex/gender-theoretical concepts into future studies offers great potential to increase the validity of research findings, thus making them more useful for prevention efforts, health promotion, and health care.
Topics: Blood Pressure; Environmental Exposure; Female; Humans; Hypertension; Male; Myocardial Ischemia; Noise
PubMed: 34574779
DOI: 10.3390/ijerph18189856 -
Frontiers in Nutrition 2022Polysaccharides have a variety of biological activities, and in the anti-tumor field, they produce tumor suppressive effects by regulating the polarization of... (Review)
Review
Polysaccharides have a variety of biological activities, and in the anti-tumor field, they produce tumor suppressive effects by regulating the polarization of tumor-associated macrophages (TAMs). In immunotherapy, it has significant activities in modulating cytokines and antibody production. We reviewed them and selected CD24, an immune target, for meta-analysis with colorectal cancer (CRC) to investigate the correlation between CD24 expression and CRC. Correlation of CD24 positive expression with clinical-pathological features: age, sex, Duke's stage, diameter, depth of invasion, degree of differentiation, and lymph node metastasis. It showed that: CD24 expression in CRC was significantly correlated with advanced nuclear grade of CRC, lymph node metastasis, Duke's stage of CRC and age of CRC patients, while there was no significant correlation with gender, tumor diameter and invasion depth. The aim is to clarify the specific mechanism of polysaccharide immune anti-tumor, combined with targeted site-specific anti-solid tumor.
PubMed: 35938128
DOI: 10.3389/fnut.2022.961507 -
Journal of Neural Transmission (Vienna,... Mar 2023The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone... (Review)
Review
The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone pathways) may increase the possibility of the emergence of autism is complementary to the hypothesis that female individuals are intrinsically less likely to develop autism. Empirical evidence for the mechanistic roles of in utero steroid hormones in autism etiology is accumulating but inconsistent. We conducted a systematic review using rigorous criteria for the measurements of steroids and vitamin D exposure, to summarize the potential contributing roles of prenatal and early postnatal steroids and vitamin D alterations to the emergence of autism. We searched PubMed, PsychInfo, Scopus, and included 22 studies for qualitative synthesis. Among them, six studies examined the association of autism diagnoses in offspring and levels of steroids and precursor steroid hormones in the fetal environment, eight studies examined the associations between autism and maternal and fetal blood vitamin D levels during pregnancy and at birth, and eight studies examined the associations between offspring autism diagnoses and maternal hyperandrogenemia diagnosed before pregnancy. We identified promising and complex results regarding the relations between steroid metabolism and autism. The interpretation of findings was limited by the mostly observational study designs, insufficient investigation of the effects of offspring sex, confounders and their cumulative effects on the development of the child, and unclear impact of the timing of steroids exposure and their effects on fetal neurodevelopment.
Topics: Child; Pregnancy; Infant, Newborn; Male; Humans; Female; Vitamin D; Autistic Disorder; Incidence; Family; Hormones; Observational Studies as Topic
PubMed: 36752873
DOI: 10.1007/s00702-022-02582-6 -
Frontiers in Endocrinology 2023Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation... (Meta-Analysis)
Meta-Analysis
CONTEXT
Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.
OBJECTIVE
This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.
DATA SOURCES
Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.
STUDY SELECTION
We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.
DATA EXTRACTION
We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.
DATA SYNTHESIS
A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).
CONCLUSIONS
Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Topics: Male; Humans; Female; Adolescent; Bone Density; Leptin; Adipokines; Adiponectin; Ghrelin; Osteoporotic Fractures
PubMed: 37181034
DOI: 10.3389/fendo.2023.1044039