Sexual Dimorphism In Response Research Articles

Plasticity in Sexual Dimorphism Enhances Adaptation of Dioecious Vallisneria natans Plants to Water Depth Change.

Sexual dimorphism in vegetative and reproductive traits is associated with contrasting strategies of males and females for response to varied environmental conditions, causing sex-specific reproduction success and consequently long-distance dispersal and colonization. Aquatic plants usually exhibit rich phenotypic plasticity and great diversity in reproductive systems, but the influence of aquatic conditions on the plasticity of sexual dimorphism has received less attention. Using a common garden experiment with dioecious submerged plant Vallisneria natans grown at various water depths simulating different light availability, we measured variations in 20 traits for females and 19 traits for males (total = 540 plants from 30 seed families) including morphology, reproductive traits and photosynthesis. We investigated sex-specific plastic responses and variation of sexual dimorphism in response to water depth change. Females displayed much greater leaf length, vegetative biomass and resource allocation to reproduction than males at all depths, whereas spathe number and gamete production per spathe displayed reverse pattern. Besides most traits in each sex (16 in female and 12 in male) showing striking phenotypic plasticity, the degree of sexual dimorphism increased significantly for total biomass and reproductive investment, but decreased for leaf length, spathe number and flowering ramet percentage in low light and deep water. Females varied more than males in leaf length, total biomass, reproductive investment, length and biomass of reproductive organs and rate of photosynthesis in response to decreased underwater light availability, suggesting that female has greater plasticity than male. These findings illustrated considerable plasticity in the degree of sexual dimorphism in a variety of vegetative and reproductive traits across different environments driven by the contrasting reproductive functions of the sexes in relation to pollen and seed dispersal. Females of V. natans responded more plastically than males to low light conditions resulted from water depth variation in either aboveground vegetative growth or reproduction. This study provides novel insight into adaptive strategies of submerged dioecious macrophytes to survive and increase fitness in freshwater habitats.

Sex-specific lipid molecular signatures in obesity-associated metabolic dysfunctions revealed by lipidomic characterization in ob/ob mouse

The response to overfeeding is sex dependent, and metabolic syndrome is more likely associated to obesity in men or postmenopausal women than in young fertile women. We hypothesized that obesity-induced metabolic syndrome is sex dependent due to a sex-specific regulation of the fatty acid (FA) synthesis pathways in liver and white adipose depots. We aimed to identify distinctive molecular signatures between sexes using a lipidomics approach to characterize lipid species in liver, perigonadal adipose tissue, and inguinal adipose tissue and correlate them to the physiopathological responses observed. Males had less total fat but lower subcutaneous on visceral fat ratio together with higher liver weight and higher liver and serum triglyceride (TG) levels. Males were insulin resistant compared to females. Fatty acid (FA) and TG profiles differed between sexes in both fat pads, with longer chain FAs and TGs in males compared to that in females. Remarkably, hepatic phospholipid composition was sex dependent with more abundant lipotoxic FAs in males than in females. This may contribute to the sexual dimorphism in response to obesity towards more metaflammation in males. Our work presents an exhaustive novel description of a sex-specific lipid signature in the pathophysiology of metabolic disorders associated with obesity in ob/ob mice. These data could settle the basis for future pharmacological treatment in obesity.

Abstract WMP76: Sexually Dimorphic Response to Stroke of miR-181a and miR-200c in Aged Mice

Background: Stroke is a sexually dimorphic disease with age-dependent sex differences in incidence, prevalence, and outcome. Delineating the molecular mechanisms that determine sexual dimorphism in stroke is necessary to overcome translational barriers and advance the development of novel stroke treatments. Non-coding RNAs, including microRNAs ( miRs ), are upstream regulators of genes that regulate cell survival. In young adult male animals, miR-181a and miR-200c have been established as central regulators in the cellular response to stroke, however their role in females or aged animal cohorts represents a critical knowledge gap. Therefore, in the present study we investigated the response of miR-181a and miR-200c in the brain after stroke in aged male and female mice. Methods: Aged (20 month old) male and female mice were subjected to 1h middle cerebral artery occlusion (MCAO) followed by 24h reperfusion. RT-qPCR, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) were used to quantify and localize post-MCAO cellular expression of miR-181a and miR-200c. Results: There was no baseline difference in miR-181a between sexes, however miR-200c expression was ~3-fold higher at baseline in female animals versus males. MCAO induced ~2-fold increase in miR-181a in male animals but post-MCAO expression remained unchanged in females. In contrast, miR-200c expression increased by ~16-fold in males and ~4-fold in females. At baseline, miR-181a and miR-200c primarily localized to cortical neurons (NeuN+). In response to MCAO astrocyte reactivity (GFAP+) coincided with robust expression of miR-200c in both males and females. Conclusions: MiR-181a and miR-200c exhibit sexual dimorphism in response to stroke. Augmented expression of miR-200c appears secondary to astrocyte reactivity. Future experiments will determine if inhibition of miR-181a and miR-200c are protective against ischemic stroke in aged animals.

Sexual dimorphism in response to herbivory and competition in the dioecious herb Spinacia oleracea

Sexual dimorphism is common in dioecious plant species and is usually attributed to different cost of reproduction associated with male and female functions. Differences in growth and performance between male and female plants may be accentuated under stress, potentially leading to sex-ratio biases and affecting population growth. Environmental stress involves multiple factors that often occur simultaneously. Among different stress combinations that occur in field conditions, competition and herbivory and their interaction are key biotic factors that can affect plant growth and performance. Here, we conducted a glasshouse experiment in Cardiff, UK, using the cultivated spinach, Spinacia oleracea, as a model system to study sexual dimorphism in intra- and inter-specific competitive ability and in response to herbivory by a generalist herbivore Helix aspersa. We found stronger inter- than intra-specific competition: growth (above-ground biomass) and chlorophyll content of male and female plants was reduced when growing with Brassica oleracea, but not when growing with conspecifics. In the absence of herbivory, females growing with same-sex neighbour had greater root biomass than males; whilst herbivory reduced root biomass significantly only in females competing with same sex neighbours. Plant damage caused by herbivores was similar when growing with male or female conspecifics but greater when growing with B. oleracea. Finally, plant damage caused by herbivores did not differ between male and female plants; however, males increased their allocation to roots and reduced their chlorophyll content after damage. Our results showed that sexual dimorphism occurs in S. oleracea, despite being a worldwide crop, selectively bred for its edible leaves. In particular, our results suggest stronger same-sex competition for females and greater tolerance to herbivory in males than in females of S. oleracea..

Sex-specific long-term blood pressure regulation: Modeling and analysis

Hypertension is a global health challenge: it affects one billion people worldwide and is estimated to account for >60% of all cases or types of cardiovascular disease. In part because sex differences in blood pressure regulation mechanisms are not sufficiently well understood, fewer hypertensive women achieve blood pressure control compared to men, even though compliance and treatment rates are generally higher in women. Thus, the objective of this study is to identify which factors contribute to the sexual dimorphism in response to anti-hypertensive therapies targeting the renin angiotensin system (RAS). To accomplish that goal, we develop sex-specific blood pressure regulation models. Sex differences in the RAS, baseline adosterone level, and the reactivity of renal sympathetic nervous activity (RSNA) are represented. A novel aspect of the model is the representation of sex-specific vasodilatory effect of the bound angiotensin II type two receptor (AT2R-bound Ang II) on renal vascular resistance. Model simulations suggest that sex differences in RSNA are the largest cause of female resistance to developing hypertension due to the direct influence of RSNA on afferent arteriole resistance. Furthermore, the model predicts that the sex-specific vasodilatory effects of AT2R-bound Ang II on renal vascular resistance may explain the higher effectiveness of angiotensin receptor blockers in treating hypertensive women (but not men), compared to angiotensin converting enzyme inhibitors.

Exposure to maternal obesity alters gene expression in the preimplantation ovine conceptus

BackgroundEmbryonic and fetal exposure to maternal obesity causes several maladaptive morphological and epigenetic changes in exposed offspring. The timing of these events is unclear, but changes can be observed even after a short exposure to maternal obesity around the time of conception. The hypothesis of this work is that maternal obesity influences the ovine preimplantation conceptus early in pregnancy, and this exposure will affect gene expression in embryonic and extraembryonic tissues.ResultsObese and lean ewe groups were established by overfeeding or normal feeding, respectively. Ewes were then bred to genetically similar rams. Conceptuses were collected at day 14 of gestation. Morphological assessments were made, conceptuses were sexed by genomic PCR analysis, and samples underwent RNA-sequencing analysis. While no obvious morphological differences existed between conceptuses, differentially expressed genes (≥ 2-fold; ≥ 0.2 RPKM; ≤ 0.05 FDR) were detected based on maternal obesity exposure (n = 21). Also, differential effects of maternal obesity were noted on each conceptus sex (n = 347). A large portion of differentially expressed genes were associated with embryogenesis and placental development.ConclusionsFindings reveal that the preimplantation ovine conceptus genome responds to maternal obesity in a sex-dependent manner. The sexual dimorphism in response to the maternal environment coupled with changes in placental gene expression may explain aberrations in phenotype observed in offspring derived from obese females.

Sex differences in lifespan extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling.

SummaryInterventions that extend lifespan in mice can show substantial sexual dimorphism. Here, we show that male‐specific lifespan extension with two pharmacological treatments, acarbose (ACA) and 17‐α estradiol (17aE2), is associated, in males only, with increased insulin sensitivity and improved glucose tolerance. Females, which show either smaller (ACA) or no lifespan extension (17aE2), do not derive these metabolic benefits from drug treatment. We find that these male‐specific metabolic improvements are associated with enhanced hepatic mTORC2 signaling, increased Akt activity, and phosphorylation of FOXO1a – changes that might promote metabolic health and survival in males. By manipulating sex hormone levels through gonadectomy, we show that sex‐specific changes in these metabolic pathways are modulated, in opposite directions, by both male and female gonadal hormones: Castrated males show fewer metabolic responses to drug treatment than intact males, and only those that are also observed in intact females, while ovariectomized females show some responses similar to those seen in intact males. Our results demonstrate that sex‐specific metabolic benefits occur concordantly with sexual dimorphism in lifespan extension. These sex‐specific effects can be influenced by the presence of both male and female gonadal hormones, suggesting that gonadally derived hormones from both sexes may contribute to sexual dimorphism in responses to interventions that extend mouse lifespan.

Sex- and structure-specific differences in antioxidant responses to methylmercury during early development

Methylmercury (MeHg) is a ubiquitous environmental contaminant and neurotoxin, particularly hazardous to developing and young individuals. MeHg neurotoxicity during early development has been shown to be sex-dependent via disturbances in redox homeostasis, a key event mediating MeHg neurotoxicity. Therefore, we investigated if MeHg-induced changes in key systems of antioxidant defense are sex-dependent. C57BL/6J mice were exposed to MeHg during the gestational and lactational periods, modeling human prenatal and neonatal exposure routes. Dams were exposed to 5ppm MeHg via drinking water from early gestational period until postnatal day 21 (PND21). On PND21 a pair of siblings (a female and a male) from multiple (5–6) litters were euthanized and tissue samples were taken for analysis. Cytoplasmic and nuclear extracts were isolated from fresh cerebrum and cerebellum and used to determine thioredoxin (Trx) and glutathione (GSH) levels, as well as thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities. The remaining tissue was used for mRNA analysis. MeHg-induced antioxidant response was not uniform for all the analyzed antioxidant molecules, and sexual dimorphism in response to MeHg treatment was evident for TrxR, Trx and GPx. The pattern of response, namely a decrease in males and an increase in females, may impart differential and sex-specific susceptibility to MeHg. GSH levels were unchanged in MeHg treated animals and irrespective of sex. Trx was reduced only in nuclear extracts from male cerebella, exemplifying a structure-specific response. Results from the gene expression analysis suggest posttranscriptional mechanism of sex-specific regulation of the antioxidant response upon MeHg treatment. The study demonstrates for the first time sex-and structure-specific changes in the response of the thioredoxin system to MeHg neurotoxicity and suggests that these differences in antioxidant responses might impart differential susceptibility to developmental MeHg exposure.

Sex and heavy metals: Study of sexual dimorphism in response to soil pollution

In dioecious plants, males and females often show distinct morphological, physiological and life history traits as result of their different demands for reproduction. Such sexual dimorphism is likely to be accentuated under stressful conditions, such as that imposed by exposure to heavy metals. However little is known about the response of dioecious plants to stress by heavy metals. Here we use the dioecious herb Silene latifolia to investigate the growth and reproduction of males and females growing in soil polluted with either Cu or Cd. We also examined whether the sexes differed in the patterns of metal accumulation in their tissues. Patterns of biomass allocation to reproduction, roots, leaves and shoots (stem and leaves) were compared in male and female S. latifolia plants that were harvested after growing for 14 weeks in different soil conditions (non-polluted soil, Cu-polluted soil and Cd-polluted soil). In addition, patterns of metal accumulation between the sexes were also compared post-harvest by analysing the metal content in their tissues. Overall, metals decreased plants’ total dry mass allocated to leaves and to roots- particularly in males. Females accumulated more Cu in their tissues. However, this did not seem to correspond with females performing worse (in terms of growth and reproduction) than males when growing in soil polluted with this metal. Despite males and females having similar levels of Cd in their tissues, males seemed to have lower tolerance to this metal, as indicated by a lower total and leaf dry mass than females, and also by a lower number of flowers when growing in Cd-polluted soil. We also found contrasting differences in female seed production due to heavy metals, with number of seeds (but not mass) decreasing with Cu and increasing with Cd. Our results indicate the presence of sexual dimorphism in response to heavy metals, with the sexes differing in both patterns of accumulation and tolerance.

Sexual dimorphism in biomedical research: a call to analyse by sex

Despite the huge body of evidence that males and females have very different immune systems and respond differently to immune challenge, few biomedical studies consider sex in their analyses. This editorial discusses the underlying biology behind immunological sex differences, their effects on immunity to infections and vaccines, and the reasons why sex differences are frequently overlooked in biomedical research. Readers are urged to design their future studies in order to analyse by sex, and to analyse existing datasets by sex. The information gained is likely to be of considerable importance in our current understanding of immune mechanisms. Sex refers to the intrinsic characteristics that distinguish males from females, whereas gender refers to the socially determined behaviour, roles or activities that males and females adopt. Male and female immune systems are not equal, leading to clear sexual dimorphism in response to infections and vaccination. In 2010, Nature featured a series of articles aimed at raising awareness regarding the inherent sex bias in modern day biomedical research and yet little has changed since that time. They comment that modern day medical practice is less evidencebased for women than for men due to a sex bias towards the study of males in biomedical research. They further suggest that journals and funders should insist on studies being conducted in both sexes, or that authors should state the sex of animals used in their studies. Unfortunately this was not widely adopted. This editorial will discuss the literature regarding sex differences in immunity to infections and vaccines and urge the readership to consider sex in their future biomedical studies. Even before they are born, intrauterine differences begin to differentially shape male and female immune systems. The male intrauterine environment is more inflammatory than that of females, male fetuses produce more androgens and have higher IgE levels, all of which lead to sexual dimorphism before birth. Furthermore, male fetuses have been shown to undergo more epigenetic changes than females with decreased methylation of many immune response genes, probably due to physiological differences. The X chromosome contains numerous immune response genes, such as toll-like receptors 7 and 8, multiple cytokine receptors, genes involved in T cell and B cell activity, and transcriptional and translational regulatory factors; while the Y chromosome encodes for a number of inflammatory pathway genes that can only be expressed in males. Females have two X chromosomes, one of which is inactivated, usually leading to expression of the wild type gene. X inactivation is incomplete or variable, which is thought to contribute to greater inflammatory responses among females. The immunological X and Y chromosome effects will begin to manifest in utero leading the sex differences in immunity from birth, which continue throughout life. MicroRNAs (miRNAs) regulate physiological processes, including cell growth, differentiation, metabolism and apoptosis. Males and females differ in their miRNA expression, even in embryonic stem cells; oestrogens and testosterone can regulate miRNAs expression, although testosterone is thought to work via its conversion to oestradiol; and the X chromosome is particularly enriched in miRNAs involved in immunity. All these sex-differential miRNA factors likely contribute to sex differences in the prevalence, pathogenesis and outcome of infections and vaccination. Females are born with higher oestriol concentrations than males, while males have more testosterone. Shortly after birth, male infants undergo a transient activation of the hypothalamo-pituitary-gonadal axis, characterised by a testosterone surge, while the female effect is variable. This so called ‘mini-puberty’ peaks at approximately 3 months of age. Once puberty begins, the ovarian hormones such as oestrogen dominate in females, while testicular-derived androgens dominate in males. Many immune cells express sex hormone receptors, allowing the sex hormones to influence immunity. Very broadly, oestrogens are Th2 biasing and pro-inflammatory, whereas testosterone is Th1 skewing and immunosuppressive. Thus sex steroids undoubtedly play a major role in sexual dimorphism in immunity throughout life. Numerous sex differences in susceptibility to infections have been described in the literature. Males fare worse during sepsis; they are more susceptible to certain bacterial infections such as invasive pneumococcal disease, group A streptococcal pharyngitis, and enterohaemorrhagic E. coli and campylobacter diarrhoea; and pulmonary tuberculosis is more prevalent among adult males. By contrast, females suffer more Mycoplasma pneumoniae and Bordetella pertussis infections. In general, viral infections are more prevalent

Bone plasticity in response to exercise is sex-dependent in rats.

PurposeTo characterize the potential sexual dimorphism of bone in response to exercise.MethodsYoung male and female Wistar rats were either submitted to 12 weeks of exercise or remained sedentary. The training load was adjusted at the mid-trial (week 6) by the maximal speed test. A mechanical test was performed to measure the maximal force, resilience, stiffness, and fracture load. The bone structure, formation, and resorption were obtained by histomorphometric analyses. Type I collagen (COL I) mRNA expression and tartrate-resistant acid phosphatase (TRAP) mRNA expression were evaluated by quantitative real-time PCR (qPCR).ResultsThe male and female trained rats significantly improved their maximum speed during the maximal exercise test (main effect of training; p<0.0001). The male rats were significantly heavier than the females, irrespective of training (main effect of sex; p<0.0001). Similarly, both the weight and length of the femur were greater for the male rats when compared with the females (main effect of sex; p<0.0001 and p<0.0001, respectively). The trabecular volume was positively affected by exercise in male and female rats (main effect of training; p = 0.001), whereas the trabecular thickness, resilience, mineral apposition rate, and bone formation rate increased only in the trained males (within-sex comparison; p<0.05 for all parameters), demonstrating the sexual dimorphism in response to exercise. Accordingly, the number of osteocytes increased significantly only in the trained males (within-sex comparison; p<0.05). Pearson’s correlation analyses revealed that the COL I mRNA expression and TRAP mRNA expression were positively and negatively, respectively, related to the parameters of bone remodeling obtained from the histomorphometric analysis (r = 0.59 to 0.85; p<0.05).ConclusionExercise yielded differential adaptations with respect to bone structure, biomechanical proprieties, and molecular signaling in male and female rats.

Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.

Selection in a fluctuating environment and the evolution of sexual dimorphism in the seed beetle Callosobruchus maculatus

Temperature changes in the environment, which realistically include environmental fluctuations, can create both plastic and evolutionary responses of traits. Sexes might differ in either or both of these responses for homologous traits, which in turn has consequences for sexual dimorphism and its evolution. Here, we investigate both immediate changes in and the evolution of sexual dimorphism in response to a changing environment (with and without fluctuations) using the seed beetle Callosobruchus maculatus. We investigate sex differences in plasticity and also the genetic architecture of body mass and developmental time dimorphism to test two existing hypotheses on sex differences in plasticity (adaptive canalization hypothesis and condition dependence hypothesis). We found a decreased sexual size dimorphism in higher temperature and that females responded more plastically than males, supporting the condition dependence hypothesis. However, selection in a fluctuating environment altered sex-specific patterns of genetic and environmental variation, indicating support for the adaptive canalization hypothesis. Genetic correlations between sexes (r(MF) ) were affected by fluctuating selection, suggesting facilitated independent evolution of the sexes. Thus, the selective past of a population is highly important for the understanding of the evolutionary dynamics of sexual dimorphism.

Gender, Brain-Derived Neurotrophic Factor Val66Met, and Frequency of Methamphetamine Use

Frequency of pretreatment methamphetamine (MA) use is an important predictor of outcomes of treatment for MA dependence. Preclinical studies suggest females self-administer more MA than males, but few clinical studies have examined potential sex differences in the frequency of MA use. Estrogen increases expression of brain-derived neurotrophic factor (BDNF), which has effects on MA-induced striatal dopamine release and protects against MA-induced neurotoxicity. We examined potential effects of sex, the Val66Met polymorphism in BDNF, and their interaction on frequency of MA use among 60 Caucasian MA-dependent volunteers screening for a clinical trial. Data was taken from 60 Caucasian MA-dependent volunteers screening for a clinical trial. Females reported significantly more pretreatment days with MA use in the past 30 days than males. There was a significant interaction between sex and BDNF Val66Met, with the highest frequency of MA use among females with Val/Val genotype. These results, although preliminary, add to the literature documenting sexual dimorphism in response to stimulants, including MA, and suggest a potential biological mechanism involving BDNF that might contribute to these differences. Additional research characterizing the biological basis of altered response to MA among females is warranted.

Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent

Context: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse.Objective: To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure.Materials and Methods: Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 µg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. Results: DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP.Conclusions: Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies.

Meiotic Checkpoints: Repair or Removal?

Defects in meiosis can produce different checkpoint responses in female and male animals, suggesting that meiotic checkpoints exhibit sexual dimorphism. A recent study in Caenorhabditis elegans indicates that meiotic checkpoint activation is similar between the sexes and the primary difference lies in the downstream consequences.

Sexual Dimorphism in Mouse Metanephroi Exposed to 17β-Estradiol in vitro

17β-Estradiol, the most potent circulating estrogen, has been shown to greatly impact on the development and formation of tissues of the urogenital tract. The adult kidney has previously been shown to be highly responsive to 17β-estradiol stimulation. However, the direct effect of 17β-estradiol on kidney development remains unclear. Aim: To investigate the direct effect of 17β-estradiol on male and female metanephric kidney development. Methods: Whole embryonic-day-12.5 (E12.5) C57Bl/6 male and female mouse metanephroi were cultured in the presence of varying concentrations of 17β-estradiol (0.1–5.0 nM) for 72 h. Metanephric development was assessed using immunofluorescence labeling techniques. The real-time polymerase chain reaction was used to investigate estrogen receptor-α (ERα), glial-cell-line-derived neurotrophic factor (GDNF) and its associated receptor cRET, transforming growth factor-β (TGFβ1), TGFβ2 and TGFβ3 mRNA expression levels. Results:ERα was present in developing metanephroi at E12.5; however, ERβ was absent. No significant sex difference in ERα mRNA expression was observed. Significant increases in the number of ureteric branch points, terminal tips and developing glomeruli were observed in female metanephroi cultured in the presence of 1.0 and 5.0 nM 17β-estradiol. Conversely, no significant effect was observed in male metanephroi cultured with 17β-estradiol. GDNF and cRET mRNA expression was increased in both male and female metanephroi, whilst TGFβ1 and TGFβ2 mRNA expression was decreased following culture in the presence of 17β-estradiol. Conclusion: This study is the first to establish that the mouse metanephros displays a sexual dimorphism in response to specific concentrations of estrogens.

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF- or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss

Aneuploidy, a chromosomal numerical abnormality in the conceptus or fetus, occurs in at least 5% of all pregnancies and is the leading cause of early pregnancy loss in humans. Accumulating evidence now suggests that the correct segregation of chromosomes is affected by events occurring in prophase during meiosis I. These events include homologous chromosome pairing, sister-chromatid cohesion, and meiotic recombination. In our current study, we show that mutations in SYCP3, a gene encoding an essential component of the synaptonemal complex that is central to the interaction of homologous chromosomes, are associated with recurrent pregnancy loss. Two out of 26 women with recurrent pregnancy loss of unknown cause were found to carry independent heterozygous nucleotide alterations in this gene, neither of which was present among a group of 150 fertile women. Analysis of transcripts from minigenes harboring each of these two mutations revealed that both affected normal splicing, possibly resulting in the production of C-terminally mutated proteins. The mutant proteins were found to interact with their wild-type counterpart in vitro and inhibit the normal fiber formation of the SYCP3 protein when coexpressed in a heterologous system. These data suggest that these mutations are likely to generate an aberrant synaptonemal complex in a dominant-negative manner and contribute to abnormal chromosomal behavior that might lead to recurrent miscarriage. Combined with the fact that similar mutations have been previously identified in two males with azoospermia, our current data suggest that sexual dimorphism in response to meiotic disruption occurs even in humans.

Renal Ischemia: Does Sex Matter?

Renal ischemia is a common complication in the perioperative period that leads to a high rate of morbidity and mortality. As in other forms of ischemia (i.e., cardiac, neurologic), the incidence and outcome of renal ischemia is strikingly sex-specific. Sexual dimorphism in response to renal injury has been noted for many years, but is now the subject of both clinical and experimental research. Clinically, women experience a lower incidence of perioperative acute renal failure, with the exception of cardiac surgery. Experimental science is now producing tantalizing clues that sex steroids, both male and female, play a role in the kidney's response to ischemia. In this review, we evaluated sex differences in perioperative renal failure and in the pathophysiology of renal ischemia/reperfusion injury. Although much work remains to characterize the biological mechanisms involved, the data are sufficient to support consideration of gender and the use of medications that impact steroid availability in the perioperative plan of care.