Browsing by Subject "Sex Characteristics"

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Open Access
A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors.
(Proc Natl Acad Sci U S A, 2000-11-07) Krebs, CJ; Jarvis, ED; Chan, J; Lydon, JP; Ogawa, S; Pfaff, DW
The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian steroid hormones estradiol (E) and progesterone (P). These receptors function as transcription factors to alter the expression of target genes. To discover behaviorally relevant genes targeted by E and P in the VMH, we used the differential display PCR to identify messenger RNAs that are differentially expressed in the hypothalamus of ovariectomized (ovx) rats treated with E alone compared with ovariectomized rats treated with E and P. We show here that one interesting mRNA within the hypothalamus that is repressed by P after E priming encodes the protein 25-Dx, the rat homolog of the human membrane-associated P-binding protein Hpr6.6. Neurons in the brain containing the highest levels of 25-Dx are located in several nuclei of the basal forebrain, including the VMH. 25-Dx expression is also higher in the hypothalamus of female P receptor "knockout" mice than in their wild-type littermates. These findings suggest a mechanism in which the activation of nuclear P receptor represses expression of a membrane P receptor, 25-Dx, during lordosis facilitation.
Open Access
A strategic research alliance: Turner syndrome and sex differences.
(American journal of medical genetics. Part C, Seminars in medical genetics, 2019-03) San Roman, Adrianna K; Page, David C; Page, David C
Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (e.g., 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy. However, the molecular mechanisms by which sex chromosome constitution impacts phenotypes at the cellular, tissue, and organismal levels remain largely unexplored. Thus, emerges a fundamental question connecting the study of sex differences and sex chromosome aneuploidy syndromes: How does sex chromosome constitution influence phenotype? Here, we focus on Turner syndrome (TS), associated with the 45,X karyotype, and its synergies with the study of sex differences. We review findings from evolutionary studies of the sex chromosomes, which identified genes that are most likely to contribute to phenotypes as a result of variation in sex chromosome constitution. We then explore strategies for investigating the direct effects of the sex chromosomes, and the evidence for specific sex chromosome genes impacting phenotypes. In sum, we argue that integrating the study of TS with sex differences offers a mutually beneficial alliance to identify contributions of the sex chromosomes to human development, health, and disease.
Open Access
Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan.
(PLoS Genet, 2014-01) Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina; Arbeeva, Liubov; Ukraintseva, Svetlana V; Stallard, Eric; Christensen, Kaare; Schupf, Nicole; Province, Michael A; Yashin, Anatoli I
Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND). The analyses show that women's lifespan is more sensitive to the e4 allele than men's in all these populations. A highly significant adverse effect of the e4 allele is limited to women with moderate lifespan of about 70 to 95 years in two FHS cohorts and the LLFS with relative risk of death RR = 1.48 (p = 3.6 × 10(-6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans increasing the risks of death of the e4 carriers with cancer two-fold compared to the non-e4 carriers, i.e., RR = 2.07 (p = 5.0 × 10(-7)). The results suggest a pivotal role of non-sex-specific cancer as a nonlinear modulator of survival in this sample that increases the risk of death of the ApoE4 carriers by 150% (p = 5.3 × 10(-8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms.
Open Access
Developmental nicotine exposure and masculinization of the rat preoptic area.
(Neurotoxicology, 2022-03) Joglekar, Rashmi; Cauley, Marty; Lipsich, Taylor; Corcoran, David L; Patisaul, Heather B; Levin, Edward D; Meyer, Joel N; McCarthy, Margaret M; Murphy, Susan K
Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.
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Differences in the cognitive skills of bonobos and chimpanzees.
(PLoS One, 2010-08-27) Herrmann, Esther; Hare, Brian; Call, Josep; Tomasello, Michael
While bonobos and chimpanzees are both genetically and behaviorally very similar, they also differ in significant ways. Bonobos are more cautious and socially tolerant while chimpanzees are more dependent on extractive foraging, which requires tools. The similarities suggest the two species should be cognitively similar while the behavioral differences predict where the two species should differ cognitively. We compared both species on a wide range of cognitive problems testing their understanding of the physical and social world. Bonobos were more skilled at solving tasks related to theory of mind or an understanding of social causality, while chimpanzees were more skilled at tasks requiring the use of tools and an understanding of physical causality. These species differences support the role of ecological and socio-ecological pressures in shaping cognitive skills over relatively short periods of evolutionary time.
Open Access
Female vs. male relative fatality risk in fatal motor vehicle crashes in the US, 1975-2020.
(PloS one, 2024-01) Abrams, Mitchell Z; Bass, Cameron R
Motor vehicle accidents are the leading cause of death for young adults 18-29 years old worldwide, resulting in nearly 1 million years of life lost annually in the United States. Despite improvements in vehicle safety technologies, young women are at higher risk of dying in car crashes compared with men in matched scenarios. Vehicle crash testing primarily revolves around test dummies representative of the 50th percentile adult male, potentially resulting in these differences in fatality risk for female occupants compared to males. Vehicle occupants involved in fatal car crashes were matched using seating location, vehicle type, airbag deployment, seatbelt usage, and age. The relative risk for fatality (R) between males and females was calculated using a Double Pair Comparison. Young women (20s-40s) are at approximately 20% higher risk of dying in car crashes compared with men of the same age in matched scenarios. In passenger cars, 25-year-old female occupants in passenger car crashes from 1975-2020 exhibit R = 1.201 (95% CI 1.160-1.250) compared to 25-year-old males, and R-1.117 (95% CI 1.040-1.207) for passenger car crashes from 2010-2020. This trend persists across vehicle type, airbag deployment, seatbelt use, and number of vehicles involved in a crash. Known sex-based differences do not explain this large risk differential, suggesting a need for expanded test methodologies and research strategies to address as-yet unexplored sex differences in crash fatalities. These differences should be further investigated to ensure equitable crash protection.
Open Access
Field methods for capture and measurement of three monkey species in Costa Rica.
(Folia Primatol (Basel), 1991) Glander, KE; Fedigan, LM; Fedigan, L; Chapman, C
A total of 54 free-ranging monkeys were captured and marked in Santa Rosa National Park, Costa Rica, during May 1985, and an additional 17 were captured during March 1986. The animals were darted using a blowpipe or a CO2 gun. The drugs used were Ketaset, Sernylan and Telazol. Ketaset was effective for Cebus capucinus but unsuccessful for Alouatta palliata and Ateles geoffroyi. Sernylan was successful for A. geoffroyi and A. palliata but is no longer commercially available. Telazol proved to be an excellent alternative capture drug for both A. palliata and A. geoffroyi.
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Gender differences in the risk of HIV infection among persons reporting abstinence, monogamy, and multiple sexual partners in northern Tanzania.
(PLoS One, 2008-08-27) Landman, Keren Z; Ostermann, Jan; Crump, John A; Mgonja, Anna; Mayhood, Meghan K; Itemba, Dafrosa K; Tribble, Alison C; Ndosi, Evaline M; Chu, Helen Y; Shao, John F; Bartlett, John A; Thielman, Nathan M
BACKGROUND: Monogamy, together with abstinence, partner reduction, and condom use, is widely advocated as a key behavioral strategy to prevent HIV infection in sub-Saharan Africa. We examined the association between the number of sexual partners and the risk of HIV seropositivity among men and women presenting for HIV voluntary counseling and testing (VCT) in northern Tanzania. METHODOLOGY/ PRINCIPAL FINDINGS: Clients presenting for HIV VCT at a community-based AIDS service organization in Moshi, Tanzania were surveyed between November 2003 and December 2007. Data on sociodemographic characteristics, reasons for testing, sexual behaviors, and symptoms were collected. Men and women were categorized by number of lifetime sexual partners, and rates of seropositivity were reported by category. Factors associated with HIV seropositivity among monogamous males and females were identified by a multivariate logistic regression model. Of 6,549 clients, 3,607 (55%) were female, and the median age was 30 years (IQR 24-40). 939 (25%) females and 293 (10%) males (p<0.0001) were HIV seropositive. Among 1,244 (34%) monogamous females and 423 (14%) monogamous males, the risk of HIV infection was 19% and 4%, respectively (p<0.0001). The risk increased monotonically with additional partners up to 45% (p<0.001) and 15% (p<0.001) for women and men, respectively with 5 or more partners. In multivariate analysis, HIV seropositivity among monogamous women was most strongly associated with age (p<0.0001), lower education (p<0.004), and reporting a partner with other partners (p = 0.015). Only age was a significant risk factor for monogamous men (p = 0.0004). INTERPRETATION: Among women presenting for VCT, the number of partners is strongly associated with rates of seropositivity; however, even women reporting lifetime monogamy have a high risk for HIV infection. Partner reduction should be coupled with efforts to place tools in the hands of sexually active women to reduce their risk of contracting HIV.
Open Access
Gender-specific structural abnormalities in major depressive disorder revealed by fixel-based analysis.
(NeuroImage. Clinical, 2019-01-08) Lyon, Matt; Welton, Thomas; Varda, Adrina; Maller, Jerome J; Broadhouse, Kathryn; Korgaonkar, Mayuresh S; Koslow, Stephen H; Williams, Leanne M; Gordon, Evian; Rush, A John; Grieve, Stuart M
Background
Major depressive disorder (MDD) is a chronic disease with a large global impact. There are currently no clinically useful predictors of treatment outcome, and the development of biomarkers to inform clinical treatment decisions is highly desirable.
Methods
In this exploratory study we performed fixel-based analysis of diffusion MRI data from the International Study to Predict Optimized Treatment in Depression with the aim of identifying novel biomarkers at baseline that may relate to diagnosis and outcome to treatment with antidepressant medications. Analyses used MR data from individuals with MDD (n = 221) and healthy controls (n = 67).
Results
We show focal, gender-specific differences in the anterior limb of the internal capsule (males) and bilaterally in the genu of the corpus callosum (females) associated with diagnosis. Lower fibre cross-section in the tapetum, the conduit between the right and left hippocampi, were also associated with a decreased probability of remission. Analysis of conventional fractional anisotropy showed scattered abnormalities in the corona radiata, cerebral peduncles and mid-brain which were much lower in total volume compared to fixel-based analysis.
Conclusions
Fixel-based analysis appeared to identify different underlying abnormalities than conventional tensor-based metrics, with almost no overlap between significant regions. We show that MDD is associated with gender specific abnormalities in the genu of the corpus callosum (females) and in the anterior limb of the internal capsule (males), as well as gender-independent differences in the tapetum that predict remission. Diffusion MRI may play a key role in future guidance of clinical decision-making for MDD.
Open Access
How Female-Female Competition Affects Male-Male Competition: Insights into Postcopulatory Sexual Selection from Socially Polyandrous Species.
(The American naturalist, 2023-03) Lipshutz, Sara E; Torneo, Samuel J; Rosvall, Kimberly A
AbstractSexual selection is a major driver of trait variation, and the intensity of male competition for mating opportunities has been linked with sperm size across diverse taxa. Mating competition among females may also shape the evolution of sperm traits, but the effect of the interplay between female-female competition and male-male competition on sperm morphology is not well understood. We evaluated variation in sperm morphology in two species with socially polyandrous mating systems, in which females compete to mate with multiple males. Northern jacanas (Jacana spinosa) and wattled jacanas (J. jacana) vary in their degree of social polyandry and sexual dimorphism, suggesting species differences in the intensity of sexual selection. We compared mean and variance in sperm head, midpiece, and tail length between species and breeding stages because these measures have been associated with the intensity of sperm competition. We found that the species with greater polyandry, northern jacana, has sperm with longer midpieces and tails as well as marginally lower intraejaculate variation in tail length. Intraejaculate variation was also significantly lower in copulating males than in incubating males, suggesting flexibility in sperm production as males cycle between breeding stages. Our results indicate that stronger female-female competition for mating opportunities may also shape more intense male-male competition by selecting for longer and less variable sperm traits. These findings extend frameworks developed in socially monogamous species to reveal that sperm competition may be an important evolutionary force layered atop female-female competition for mates.
Open Access
Introduction to sex differences in neurotoxic effects.
(Neurotoxicology and teratology, 2021-01) Levin, Edward D; Dow-Edwards, Diana; Patisaul, Heather
Open Access
Let's talk about sex characteristics-As a risk factor for invasive fungal diseases.
(Mycoses, 2022-06) Egger, Matthias; Hoenigl, Martin; Thompson, George R; Carvalho, Agostinho; Jenks, Jeffrey D
Biological sex, which comprises differences in host sex hormone homeostasis and immune responses, can have a substantial impact on the epidemiology of infectious diseases. Comprehensive data on sex distributions in invasive fungal diseases (IFDs) are lacking. In this review, we performed a literature search of in vitro/animal studies, clinical studies, systematic reviews and meta-analyses of invasive fungal infections. Females represented 51.2% of invasive candidiasis cases, mostly matching the proportions of females among the general population in the United States and Europe (>51%). In contrast, other IFDs were overrepresented in males, including invasive aspergillosis (51% males), mucormycosis (60%), cryptococcosis (74%), coccidioidomycosis (70%), histoplasmosis (61%) and blastomycosis (66%). Behavioural variations, as well as differences related to biological sex, may only in part explain these findings. Further investigations concerning the association between biological sex/gender and the pathogenesis of IFDs are warranted.
Open Access
Morphometrics and growth in captive aye-ayes (Daubentonia madagascariensis).
(Folia Primatol (Basel), 1994) Glander, KE
Open Access
Perinatal diazinon exposure compromises the development of acetylcholine and serotonin systems.
(Toxicology, 2019-08) Slotkin, Theodore A; Skavicus, Samantha; Ko, Ashley; Levin, Edward D; Seidler, Frederic J
Organophosphate pesticides are developmental neurotoxicants. We gave diazinon via osmotic minipumps implanted into dams prior to conception, with exposure continued into the second postnatal week, at doses (0.5 or 1 mg/kg/day) that did not produce detectable brain cholinesterase inhibition. We evaluated the impact on acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT) systems in brain regions from adolescence through full adulthood. Diazinon produced deficits in presynaptic ACh activity with regional and sex selectivity: cerebrocortical regions and the hippocampus were affected to a greater extent than were the striatum, midbrain or brainstem, and females were more sensitive than males. Diazinon also reduced nicotinic ACh receptors and 5HT1A receptors, with the same regional and sex preferences. These patterns were similar to those of diazinon given in a much more restricted period (postnatal day 1-4) but were of greater magnitude and consistency; this suggests that the brain is vulnerable to diazinon over a wide developmental window. Diazinon's effects differed from those of the related organophosphate, chlorpyrifos, with regard to regional and sex selectivity, and more importantly, to the effects on receptors: chlorpyrifos upregulates nicotinic ACh receptors and 5HT receptors, effects that compensate for the presynaptic ACh deficits. Diazinon can thus be expected to have worse neurodevelopmental outcomes than chlorpyrifos. Further, the disparities between diazinon and chlorpyrifos indicate the problems of predicting the developmental neurotoxicity of organophosphates based on a single compound, and emphasize the inadequacy of cholinesterase inhibition as an index of safety.
Open Access
Putting together phylogenetic and ontogenetic perspectives on empathy.
(Dev Cogn Neurosci, 2012-01) Decety, Jean; Svetlova, Margarita
The ontogeny of human empathy is better understood with reference to the evolutionary history of the social brain. Empathy has deep evolutionary, biochemical, and neurological underpinnings. Even the most advanced forms of empathy in humans are built on more basic forms and remain connected to core mechanisms associated with affective communication, social attachment, and parental care. In this paper, we argue that it is essential to consider empathy within a neurodevelopmental framework that recognizes both the continuities and changes in socioemotional understanding from infancy to adulthood. We bring together neuroevolutionary and developmental perspectives on the information processing and neural mechanisms underlying empathy and caring, and show that they are grounded in multiple interacting systems and processes. Moreover, empathy in humans is assisted by other abstract and domain-general high-level cognitive abilities such as executive functions, mentalizing and language, as well as the ability to differentiate another's mental states from one's own, which expand the range of behaviors that can be driven by empathy.
Open Access
Relative growth of the limbs and trunk in sifakas: heterochronic, ecological, and functional considerations.
(Am J Phys Anthropol, 1993-12) Ravosa, MJ; Meyers, DM; Glander, KE
Limb, trunk, and body weight measurements were obtained for growth series of Milne-Edwards's diademed sifaka, Propithecus diadema edwardsi, and the golden-crowned sifaka, Propithecus tattersalli. Similar measures were obtained also for primarily adults of two subspecies of the western sifaka: Propithecus verreauxi coquereli, Coquerel's sifaka, and Propithecus verreauxi verreauxi, Verreaux's sifaka. Ontogenetic series for the larger-bodied P. d. edwardsi and the smaller-bodied P. tattersalli were compared to evaluate whether species-level differences in body proportions result from the differential extension of common patterns of relative growth. In bivariate plots, both subspecies of P. verreauxi were included to examine whether these taxa also lie along a growth trajectory common to all sifakas. Analyses of the data indicate that postcranial proportions for sifakas are ontogenetically scaled, much as demonstrated previously with cranial dimensions for all three species (Ravosa, 1992). As such, P. d. edwardsi apparently develops larger overall size primarily by growing at a faster rate, but not for a longer duration of time, than P. tattersalli and P. verreauxi; this is similar to results based on cranial data. A consideration of Malagasy lemur ecology suggests that regional differences in forage quality and resource availability have strongly influenced the evolutionary development of body-size variation in sifakas. On one hand, the rainforest environment of P. d. edwardsi imposes greater selective pressures for larger body size than the dry-forest environment of P. tattersalli and P. v. coquereli, or the semi-arid climate of P. v. verreauxi. On the other hand, as progressively smaller-bodied adult sifakas are located in the east, west, and northwest, this apparently supports suggestions that adult body size is set by dry-season constraints on food quality and distribution (i.e., smaller taxa are located in more seasonal habitats such as the west and northeast). Moreover, the fact that body-size differentiation occurs primarily via differences in growth rate is also due apparently to differences in resource seasonality (and juvenile mortality risk in turn) between the eastern rainforest and the more temperate northeast and west. Most scaling coefficients for both arm and leg growth range from slight negative allometry to slight positive allometry. Given the low intermembral index for sifakas, which is also an adaptation for propulsive hindlimb-dominated jumping, this suggests that differences in adult limb proportions are largely set prenatally rather than being achieved via higher rates of postnatal hindlimb growth.(ABSTRACT TRUNCATED AT 400 WORDS)
Open Access
Reproduction and population growth in free-ranging mantled howling monkeys.
(Am J Phys Anthropol, 1980-07) Glander, KE
Free-ranging mantled howling monkey (Alouatta palliata Gray) females experienced a regular estrus cycle averaging 16.3 days, demonstrated sexual skin changes, and participated in multiple matings before becoming pregnant. Gestation averaged 186 days. The average interval between births was 22.5 months. Sexual maturity occurred at approximately 36 and 42 months for females and males, respectively. Female age at first birth was about 3 1/2 years. Births were scattered during some years and clustered during others. The age, rank, and parity of the females affected infant survival. More female than male infants survived to one year of age. Increased population size was the result of immigration rather than births.
Open Access
Sex Differences in Biological Markers of Health in the Study of Stress, Aging and Health in Russia.
(PLoS One, 2015) Oksuzyan, Anna; Shkolnikova, Maria; Vaupel, James W; Christensen, Kaare; Shkolnikov, Vladimir M
BACKGROUND: The apparent contradiction that women live longer but have worse health than men, the so called male-female health-survival paradox, is very pronounced in Russia. The present study investigates whether men in Moscow are healthier than women at the level of biomarkers, and whether the associations between biomarkers and subjective health have sex-specific patterns. MATERIALS: Previously collected data in the study of Stress, Aging, and Health in Russia (SAHR, n = 1800) were used to examine sex differences in biomarkers and their associations with physical functioning and self-rated health. RESULTS: The present study found mixed directions and magnitudes for sex differences in biomarkers. Women were significantly disadvantaged with regard to obesity and waist circumference, whereas men had a tendency toward higher prevalence of electrocardiographic abnormalities. No sex differences were indicated in the prevalence of immunological biomarkers, and mixed patterns were found for lipid profiles. Many biomarkers were associated with physical functioning and general health. Obesity and waist circumference were related to lower physical functioning among females only, while major Q-wave abnormalities with high probabilities of myocardial infarction and atrial fibrillation or atrial flutter were associated with physical functioning and self-rated health among males only. CONCLUSION: No clear patterns of sex differences in prevalence of high-risk levels of biomarkers suggest that the male-female health-survival paradox is weaker at the level of health biomarkers. We found some evidence that certain biomarkers reflecting pathophysiological changes in the organism that do not possess acute health risks, but over many years may lead to physical disability, are associated with physical functioning and self-rated health in women, whereas others reflecting more serious life-threatening pathophysiological changes are associated with physical functioning and self-rated health in men.
Open Access
Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair.
(Cell reports, 2022-11) Ide, Shintaro; Ide, Kana; Abe, Koki; Kobayashi, Yoshihiko; Kitai, Hiroki; McKey, Jennifer; Strausser, Sarah A; O'Brien, Lori L; Tata, Aleksandra; Tata, Purushothama Rao; Souma, Tomokazu
In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. Using genetic and single-cell transcriptomic approaches in mice, we report that female sex confers striking protection against ferroptosis, which was experimentally induced in proximal tubular (PT) cells by deleting glutathione peroxidase 4 (Gpx4). Single-cell transcriptomic analyses further identify the NFE2-related factor 2 (NRF2) antioxidant protective pathway as a female resilience mechanism against ferroptosis. Genetic inhibition and pharmacological activation studies show that NRF2 controls PT cell fate and plasticity by regulating ferroptosis. Importantly, pharmacological NRF2 activation protects male PT cells from ferroptosis and improves cellular plasticity as in females. Our data highlight NRF2 as a potential therapeutic target to prevent failed renal repair after acute kidney injury in both sexes by modulating cellular plasticity.
Open Access
Sex differences in the level and rate of change of physical function and grip strength in the Danish 1905-cohort study.
(J Aging Health, 2010-08) Oksuzyan, Anna; Maier, Heiner; McGue, Matt; Vaupel, James W; Christensen, Kaare
OBJECTIVE: The study was conducted to examine sex differences in the initial level and rate of change in physical function and grip strength. METHOD: The baseline survey included 2,262 Danes born in 1905 and alive in 1998 and followed-up in 2000, 2003, and 2005. Hence, the authors fully used the power of having a cohort with multiple assessments in late life and virtually complete follow-up of lifespan (through December 2008). Latent growth curve modeling was used. RESULTS: Men had higher initial levels and rates of decline in strength score and grip strength. Lifespan was positively correlated with intercepts and slopes. DISCUSSION: The Danish data suggested that the longest-living individuals have higher initial levels of strength score and grip strength and smaller rate of change. The data further suggested that the initial level of strength score and grip strength was more predictive of mortality than the rate of change was, and the predictive effects were similar in men and women.

Browsing by Subject "Sex Characteristics"

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