Higher Expression In Females Research Articles

Functional Analysis of CPSF30 in Nilaparvata lugens Using RNA Interference Reveals Its Essential Role in Development and Survival

The brown planthopper (Nilaparvata lugens) is a major pest threatening global rice production, significantly reducing yields annually. As N. lugens increasingly develops resistance to conventional control methods, such as chemical pesticides, there is an urgent need for innovative and sustainable pest management strategies. Cleavage and Polyadenylation Specificity Factor 30 (CPSF30) is a key protein involved in mRNA 3′ end processing, yet its function in N. lugens remains poorly understood. This study aims to elucidate the role of CPSF30 in the growth and development of N. lugens and evaluate its potential as a target for RNA interference (RNAi)-based pest control strategies. We cloned and characterized the cDNA sequence of NlCPSF30, which encodes a protein of 341 amino acids containing five CCCH zinc-finger domains and two CCHC zinc-knuckle domains. Sequence alignment revealed that NlCPSF30 is highly conserved among insect species, particularly in the zinc-finger domains essential for RNA binding and processing. Phylogenetic analysis showed that NlCPSF30 is closely related to CPSF30 proteins from other hemipteran species. Expression analysis indicated that NlCPSF30 is most highly expressed in the fat body and during the adult stage, with significantly higher expression in females than in males. RNAi-mediated silencing of NlCPSF30 in third-instar nymphs resulted in severe phenotypic abnormalities, including disrupted molting and increased mortality following injection of double-stranded RNA (dsRNA) targeting NlCPSF30. Moreover, it influenced the expression of genes associated with hormone regulation, namely NlHry, NlE93, and NlKr-h1. These results suggest that NlCPSF30 is integral to critical physiological processes, with its disruption leading to increased mortality. Our findings identify NlCPSF30 as an essential gene for N. lugens’ survival and a promising target for RNAi-based pest management strategies. This study provides a valuable molecular target and theoretical insights for developing RNAi-based control methods against N. lugens.

IGF1R and FLT1 in female endothelial cells and CHD2 in male microglia play important roles in Alzheimer's disease based on gender difference analysis

ObjectiveThis study investigated sex-specific pathogenesis mechanisms in Alzheimer's disease (AD) using single-nucleus RNA sequencing (snRNA-seq) data. MethodsData from the Gene Expression Omnibus (GEO) were searched using terms “Alzheimer's Disease”, “single cell”, and “Homo sapiens”. Studies excluding APOE E4 and including comprehensive gender information with 10× sequencing methods were selected, resulting in GSE157827 and GSE174367 datasets from human prefrontal cortex samples. Sex-stratified analyses were conducted on these datasets, and the outcomes of the analysis for GSE157827 were compared with those of GSE174367. The findings were validated using expression profiling from the mouse dataset GSE85162. Furthermore, real-time PCR experiments in mice further confirmed these findings. The Seurat R package was used to identify cell types, and batch effects were mitigated using the Harmony R package. Cell proportions by sex were compared using the Mann-Whitney-Wilcoxon test, and gene expression variability was displayed with an empirical cumulative distribution plot. Differentially expressed genes were identified using the FindMarkers function with the MAST test. Transcription factors were analyzed using the RcisTarget R package. ResultsSeven cell types were identified: astrocytes, endothelial cells, excitatory neurons, inhibitory neurons, microglia, oligodendrocytes, and oligodendrocyte progenitor cells. Additionally, five distinct subpopulations of both endothelial and microglial cells were also identified, respectively. Key findings included: (1) In endothelial cells, genes involved in synapse organization, such as Insulin Like Growth Factor 1 Receptor (IGF1R) and Fms Related Receptor Tyrosine Kinase 1(FLT1), showed higher expression in females with AD. (2) In microglial cells, genes in the ribosome pathway exhibited higher expression in males without AD compared to females (with or without AD) and males with AD. (3) Chromodomain Helicase DNA Binding Protein 2 (CHD2) negatively regulated gene expression in the ribosome pathway in male microglia, suppressing AD, this finding was further validated in mice. (4) Differences between Asians and Caucasians were observed based on sex and disease status stratification. ConclusionsIGF1R and FLT1 in endothelial cells contribute to AD in females, while CHD2 negatively regulates ribosome pathway gene expression in male microglia, suppressing AD in humans and mice.

Sex biased expression of Fem-1 in larval stages suggests its function in early sex differentiation of Litopeneaus vannamei

The Pacific white shrimp Litopenaeus vannamei (L. vannamei) is an economically important species worldwide. As females exhibit a faster growth rate than males, it is crucial to understand the mechanism of sex determination and differentiation for the purpose of mono-sex breeding in shrimp. The feminization-1 gene (Fem-1) serves as a sex-determining gene in Caenorhabditis elegans, and the Fem-1 family is implicated in sex development in several crustaceans. In this study, three Fem-1 family members, namely LvFem-1a, LvFem-1b, and LvFem-1c, were identified and characterized in L. vannamei. Based on genetic sex marker, individuals were separated by sex during the early developmental stages. The expression profiles of these genes were analyzed in female or male larvae. Significant differences between females and males were observed during the early stages of development. In Zoea III or earlier stages, the expressions levels in males were significantly higher than those in females. Intriguingly, there was a shift towards higher expression in females during the mysis and post-larval stages. These findings indicate that the Zoea III stage may be crucial for sex differentiation in shrimp. In addition, the analysis of gene expression across various ovarian stages and tissues was conducted. Results showed that all three genes were highly expressed in the ovary, with particularly elevated levels in ovarian development stage II. These findings suggest that the Fem-1 genes play a critical role in early ovary development. This study is the first research focusing on the sex-specific expression of sex differentiation genes in shrimp. The obtained results provide new insights into to the role of the Fem-1 gene family in sex differentiation and gonadal development.

Proteomic Characterization of Drosophila melanogaster Proboscis.

Drosophila melanogaster flies use their proboscis to taste and distinguish edible compounds from toxic compounds. With their proboscis, flies can detect sex pheromones at a close distance or by contact. Most of the known proteins associated with probosci's detection belong to gustatory receptor families. To extend our knowledge of the proboscis-taste proteins involved in chemo-detection, we used a proteomic approach to identify soluble proteins from Drosophila females and males. This investigation, performed with hundreds of dissected proboscises, was initiated by the chromatographic separation of tryptic peptides, followed by tandem mass spectrometry, allowing for femtomole detection sensitivity. We found 586 proteins, including enzymes, that are involved in intermediary metabolism and proteins dedicated to various functions, such as nucleic acid metabolism, ion transport, immunity, digestion, and organ development. Among 60 proteins potentially involved in chemosensory detection, we identified two odorant-binding proteins (OBPs), i.e., OBP56d (which showed much higher expression in females than in males) and OBP19d. Because OBP56d was also reported to be more highly expressed in the antennae of females, this protein can be involved in the detection of both volatile and contact male pheromone(s). Our proteomic study paves the way to better understand the complex role of Drosophila proboscis in the chemical detection of food and pheromonal compounds.

Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice

The variability of severity in hypoxia-ischemia (HI)-induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0–6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci’s rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using quantitative reverse transcription polymerase chain reaction. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.

Assessing how biological sex effects tissue-resident memory T cell responses to influenza infection

Abstract The severity and outcome of influenza virus infection are dependent on various host factors including sex. During the 1918 influenza pandemic, males succumbed to viral infections more than females. Following seasonal influenza vaccination, haemagglutination inhibition titers are significantly higher in females than males. Additionally, the Tlr7 gene that recognizes influenza viruses is located on the X chromosome, resulting in higher expression in females. It is not known whether sex influences non-lymphoid tissue residency of lymphocytes during influenza infection. To explore this, we infected male and female mice intratracheally with 20 PFU influenza virus (A/PR8/H1N1). No significant change was noted in weight loss; however, females displayed a higher survival rate and milder clinical disease nine days post-infection. Lungs of female mice contained greater numbers of influenza-specific tissue-resident CD4+ T-cells compared to males. To assess the role of extra-lymphoid tissues in tissue residency in both sexes, we infected male and female lymphotoxin-a knockout (LTa KO) splenectomized mice that resulted in a total lack of all lymphoid tissues. Physiological differences trended the same for both males and females, with no significant weight difference; however, LTa KO females generated more tissue-resident CD4+ T-cells, while males displayed greater numbers of tissue-resident CD8+ T-cells. Overall, females generated a stronger immune response in the absence of lymphoid tissues in response to the virus. Taken together, our data reveal a novel sex-based effect of viral infection on tissue-resident lymphocytes and non-lymphoid tissue immunity. Supported by a grant from the W.M. Keck Foundation

Temporal and Quantitative Transcriptomic Differences Define Sexual Dimorphism in Murine Postnatal Bone Aging.

ABSTRACTTime is a central element of the sexual dimorphic patterns of development, pathology, and aging of the skeleton. Because the transcriptome is a representation of the phenome, we hypothesized that both sex and sex‐specific temporal, transcriptomic differences in bone tissues over an 18‐month period would be informative to the underlying molecular processes that lead to postnatal sexual dimorphism. Regardless of age, sex‐associated changes of the whole bone transcriptomes were primarily associated not only with bone but also vascular and connective tissue ontologies. A pattern‐based approach used to screen the entire Gene Expression Omnibus (GEO) database against those that were sex‐specific in bone identified two coordinately regulated gene sets: one related to high phosphate–induced aortic calcification and one induced by mechanical stimulation in bone. Temporal clustering of the transcriptome identified two skeletal tissue‐associated, sex‐specific patterns of gene expression. One set of genes, associated with skeletal patterning and morphology, showed peak expression earlier in females. The second set of genes, associated with coupled remodeling, had quantitatively higher expression in females and exhibited a broad peak between 3 to 12 months, concurrent with the animals' reproductive period. Results of phenome‐level structural assessments of the tibia and vertebrae, and in vivo and in vitro analysis of cells having osteogenic potential, were consistent with the existence of functionally unique, skeletogenic cell populations that are separately responsible for appositional growth and intramedullary functions. These data suggest that skeletal sexual dimorphism arises through sex‐specific, temporally different processes controlling morphometric growth and later coupled remodeling of the skeleton during the reproductive period of the animal. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sexual dimorphism of monocyte transcriptome in individuals with chronic low-grade inflammation

Sexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjusted p value (FDR) < 0.1], including genes involved in immune cell activation (e.g., CEACAM1, FCGR2B, and SLAMF7) and antigen presentation (e.g., AIM2, CD1E, and UBA1) with a higher expression in females than males. Moreover, signaling pathways of immune or inflammatory responses, including interferon (IFN) signaling [z-score = 2.45, -log(p) = 3.88], were found to be more upregulated in female versus male monocytes, based on a set of genes exhibiting sex-biased expression (p < 0.03). The contribution of IFN signaling to the sexual transcriptional differences was further confirmed by direct comparisons of the monocyte sex-biased genes with IFN signature genes (ISGs) that were previously curated in mouse macrophages. ISGs showed a greater overlap with female-biased genes than male-biased genes and a higher overall expression in female than male monocytes, particularly for the genes of antiviral and inflammatory responses to IFN. Given the role of IFN in immune defense and autoimmunity, our results suggest that sexual dimorphism in immune functions may be associated with more priming of innate immune pathways in female than male monocytes. These findings highlight the role of sex on the human immune transcriptome.

Vitellogenin gene expression in marine mussels exposed to ethinylestradiol: No induction at the transcriptional level

Vitellogenin (Vtg), a large multidomain protein precursor of egg-yolk proteins, is used as an endocrine disruption biomarker in fish, and in the last decades, its use has been extended to invertebrates like mollusks. However, it remains unclear whether invertebrate endocrine system produces Vtg in response to estrogens, like it occurs in oviparous vertebrates. In a previous study, no evidence of induction of Vtg expression at protein level was found in gonads of the marine mussel Mytilus galloprovincialis after exposure to the estrogenic chemical 17α-ethinylestradiol (EE2). In the present follow-up study, it was investigated whether there is any effect of EE2 on Vtg abundance at transcriptional level in M. galloprovincialis gonads. To this aim, RT-qPCR analysis targeting three different domains of Vtg transcript was performed on gonads of mussels that were exposed either 4 or 24 days to 100 ng/L EE2. In addition, several reference genes were analysed and a selection of these for potential use in further RT-qPCR analyses on mussel male and female gonads is provided. Results showed higher expression in females than in males for the three analysed Vtg domains, and no evidence of Vtg mRNA induction due to EE2 either in females or males. The present results, together with those obtained from previous analysis at protein level, support that Vtg is not an adequate biomarker for xenoestrogenicity in marine mussels. Additionally, nucleotide sequences of Vtg transcripts of three closely-related species from Mytilus edulis complex (M. galloprovincialis, M. edulis and M. trossulus) are provided and compared with Vtg sequences from other mollusk species to assess the level of conservation and evolutionary relationships among species.

Host plants transfer induced regulation of the chemosensory genes repertoire in the alfalfa plant bug Adelphocoris lineolatus (Goeze)

The alfalfa plant bug Adelphocoris lineolatus, an economically important pest, has representative behavioral characteristics with host plants transfer. Olfactory system is essential for insects to perceive ever-changing chemical signals in the external environment, and chemosensory genes play crucial roles in signals reception and transduction. In this work, we compared the differences in chemosensory genes expression before and after host plants transfer by constructing 12 antennal transcriptomes of male and female bugs, respectively. The results showed that the expression levels of most chemosensory genes in A. lineolatus changed to adapt to the transformation of the hosts plant. More remarkable, female bugs had more up-regulated chemosensory genes than males. Differentially expressed genes (DEGs) analysis revealed three odorant binding proteins (OBPs), three chemosensory proteins (CSPs), eight odorant receptors (ORs) and one ionotropic receptor (IR) showed significant differences when the host plant transferred. There were complex characteristics of up- and down- regulated genes in male and female adults, among which OBP19 showed higher expression in females exposing to the new host plant alfalfa, suggesting this OBP may be associated with the localization of the oviposition site. The OR54 and OR82 were up-regulated in both genders, indicating their possible roles in recognizing some alfalfa-specific volatiles. These findings will provide valuable insights in biological functions of chemosensory genes in A. lineolatus and facilitate the development of new targets for novel strategies to control the alfalfa plant bug and other herbivores.

Biomarkers Associated With Aortic Valve Calcification: Should We Focus on Sex Specific Processes?

ObjectiveCirculating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex.MethodsBlood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC.ResultsIn the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16–6.70), p = 0.022; PAPPA: OR 0.30 (0.11–0.84), p = 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12–0.80), p = 0.015; FGF23: OR 0.41 (0.170–0.991), p = 0.048; MCP1: OR 2.64 (1.02–6.81), p = 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31–116.7), p = 0.028; ST2: OR13.64 (1.21–153.33), p = 0.034].ConclusionIn this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.

The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity.

Multiple sclerosis (MS) is a putative T cell-mediated autoimmune disease. As with many autoimmune diseases, females are more susceptible than males. Sexual dimorphisms may be due to differences in sex hormones, sex chromosomes, or both. Regarding sex chromosome genes, a small percentage of X chromosome genes escape X inactivation and have higher expression in females (XX) compared with males (XY). Here, high-throughput gene expression analysis in CD4+ T cells showed that the top sexually dimorphic gene was Kdm6a, a histone demethylase on the X chromosome. There was higher expression of Kdm6a in females compared with males in humans and mice, and the four core genotypes (FCG) mouse model showed higher expression in XX compared with XY. Deletion of Kdm6a in CD4+ T cells ameliorated clinical disease and reduced neuropathology in the classic CD4+ T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis (EAE). Global transcriptome analysis in CD4+ T cells from EAE mice with a specific deletion of Kdm6a showed upregulation of Th2 and Th1 activation pathways and downregulation of neuroinflammation signaling pathways. Together, these data demonstrate that the X escapee Kdm6a regulates multiple immune response genes, providing a mechanism for sex differences in autoimmune disease susceptibility.

Octopus maya white body show sex-specific transcriptomic profiles during the reproductive phase, with high differentiation in signaling pathways.

White bodies (WB), multilobulated soft tissue that wraps the optic tracts and optic lobes, have been considered the hematopoietic organ of the cephalopods. Its glandular appearance and its lobular morphology suggest that different parts of the WB may perform different functions, but a detailed functional analysis of the octopus WB is lacking. The aim of this study is to describe the transcriptomic profile of WB to better understand its functions, with emphasis on the difference between sexes during reproductive events. Then, validation via qPCR was performed using different tissues to find out tissue-specific transcripts. High differentiation in signaling pathways was observed in the comparison of female and male transcriptomic profiles. For instance, the expression of genes involved in the androgen receptor-signaling pathway were detected only in males, whereas estrogen receptor showed higher expression in females. Highly expressed genes in males enriched oxidation-reduction and apoptotic processes, which are related to the immune response. On the other hand, expression of genes involved in replicative senescence and the response to cortisol were only detected in females. Moreover, the transcripts with higher expression in females enriched a wide variety of signaling pathways mediated by molecules like neuropeptides, integrins, MAPKs and receptors like TNF and Toll-like. In addition, these putative neuropeptide transcripts, showed higher expression in females’ WB and were not detected in other analyzed tissues. These results suggest that the differentiation in signaling pathways in white bodies of O. maya influences the physiological dimorphism between females and males during the reproductive phase.

Visualisation of Kiss1 Neurone Distribution Using a Kiss1‐CRE Transgenic Mouse

Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE‐GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss‐CRE heterozygous mice with CRE‐activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80‐90% of tdTomato positive neurones in the ARC were co‐labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato‐labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre‐optic areas and to the lateral hypothalamus.

Bisphenol A Effects on Gonadotroph Function: Disruption of Pituitary Cell-Cell Communication?

Since the publication of a joint International Programme on Chemical Safety report in 2002 assessing the scientific knowledge of endocrine disruptors, there has been a dramatic increase in both awareness of the risk they may pose and studies of potential health implications for humans and wildlife (1). Of all the endocrine disruptors studied to date, there has been considerable focus on bisphenol A (BPA), in particular on its effects on the reproductive axis (2). BPA is a widely used industrial chemical, which has been found in 95% of urine samples from adults in the United States (3), with contaminated food and water accounting for 90% of exposure (4). Although most studies have focused on the estrogenic activity of BPA, it has also been shown to bind to androgen and thyroid hormone receptors, suggesting that it may disrupt multiple endocrine systems. In the reproductive axis, BPA has been reported to adversely affect several end points of fertility, advance puberty, and induce polycystic ovarian syndrome (2). In this edition of Endocrinology, Eckstrum et al (5) describe effects of BPA on gonadotrophs during an important pituitary developmental window in neonatal mice. The authors have found that the gene encoding intracellular adhesion molecule-5 (Icam5) (also known as telencephalin) is more highly expressed in the pituitary of day-old female mice compared with their male littermates. They go on to show that the RNA and protein are predominantly expressed in gonadotrophs, with increased expression during the early postnatal period (up to d 20), with a continued higher expression in females than males. The disrupting effect of BPA on this expression is demonstrated in females and males in ex vivo cultures, and in females in vivo, with lower expression of Icam5. This work builds on previous studies describing effects on BPA exposure in utero by the same group, where different effects on the reproductive axis were described, consistent with the concept that specific windows of the development of endocrine axes may be differentially affected by the same endocrine disruptor. What is the potential role of Icam5 in normal pituitary function? Expression of this gene has previously been considered to occur only in the telencephalon, where it has a role in the regulation of the interactions between axonal protrusions and dendritic spines, which form neuronal synapses. Loss of Icam5 in knockout mice leads to a reduction in filopodia, which develop into dendritic spines (6) and increased spinal maturation, overexpression the reverse. This kind of cell-cell interaction leading to functional connectivity has been described in the pituitary, where homotypic cell networks have been shown to exist, with important roles in the regulation of cell function at both the level of secretion (7) and gene expression (8). The proteins regulating this cell network formation have not been identified, but those with a function similar to that described for ICAM5 are likely to be mediators, making it a likely candidate. In the neonate, it is possible that ICAM5 mediates the formation of the gonadotroph network described by Budry et al (9). This network begins its development before birth, and it would be interesting to determine whether there is a window of Icam5 expression in these early gonadotrophs. In the adult, ICAM5 was only found in a subset of gonadotrophs, what could be its role

Gene expression analysis at the onset of sex differentiation in turbot (Scophthalmus maximus).

BackgroundControlling sex ratios is essential for the aquaculture industry, especially in those species with sex dimorphism for relevant productive traits, hence the importance of knowing how the sexual phenotype is established in fish. Turbot, a very important fish for the aquaculture industry in Europe, shows one of the largest sexual growth dimorphisms amongst marine cultured species, being all-female stocks a desirable goal for the industry. Although important knowledge has been achieved on the genetic basis of sex determination (SD) in this species, the master SD gene remains unknown and precise information on gene expression at the critical stage of sex differentiation is lacking. In the present work, we examined the expression profiles of 29 relevant genes related to sex differentiation, from 60 up to 135 days post fertilization (dpf), when gonads are differentiating. We also considered the influence of three temperature regimes on sex differentiation.ResultsThe first sex-related differences in molecular markers could be observed at 90 days post fertilization (dpf) and so we have called that time the onset of sex differentiation. Three genes were the first to show differential expression between males and females and also allowed us to sex turbot accurately at the onset of sex differentiation (90 dpf): cyp19a1a, amh and vasa. The expression of genes related to primordial germ cells (vasa, gsdf, tdrd1) started to increase between 75–90 dpf and vasa and tdrd1 later presented higher expression in females (90-105 dpf). Two genes placed on the SD region of turbot (sox2, fxr1) did not show any expression pattern suggestive of a sex determining function. We also detected changes in the expression levels of several genes (ctnnb1, cyp11a, dmrt2 or sox6) depending on culture temperature.ConclusionOur results enabled us to identify the first sex-associated genetic cues (cyp19a1a, vasa and amh) at the initial stages of gonad development in turbot (90 dpf) and to accurately sex turbot at this age, establishing the correspondence between gene expression profiles and histological sex. Furthermore, we profiled several genes involved in sex differentiation and found specific temperature effects on their expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2142-8) contains supplementary material, which is available to authorized users.

Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males.

Assessment of the Immunohistochemical expression of EBV in oral lichen planus

Background: Oral lichen planus (OLP) is a chronic immunologic disease. The etiology of OLP is unknown, viral antigens (for example EBV) have been proposed as etiologic agents. OLP may get transformation to malignancy so research on the presence of these in OLP lesions seems to be necessary. The aim of this study was to evaluate EBV expression immunohistochemically in OLP. Materials and Methods: Tissue specimens of 30 formalin fixed, paraffin-embedded tissue Blocks histologically diagnosed oral lichen planus was performed to evaluate EBV expression. Results: Expression of EBV was detected in epithelium of (46.6%) in the study samples in (OLP). no statistically significant correlation was found with clinical parameters except for a significantly higher expression in females. Conclusions: Epstein Barr viruses were present in considerable amounts in oral lichen planus. Taking into account the potential of viruses in OLP proving or disapproving or etiological role of viruses in OLP is continuously need to be examined in further studies.

X chromosome regulation of autosomal gene expression in bovine blastocysts.

Although X chromosome inactivation in female mammals evolved to balance the expression of X chromosome and autosomal genes in the two sexes, female embryos pass through developmental stages in which both X chromosomes are active in somatic cells. Bovine blastocysts show higher expression of many X genes in XX than XY embryos, suggesting that X inactivation is not complete. Here, we reanalyzed bovine blastocyst microarray expression data from a network perspective with a focus on interactions between X chromosome and autosomal genes. Whereas male-to-female ratios of expression of autosomal genes were distributed around a mean of 1, X chromosome genes were clearly shifted towards higher expression in females. We generated gene coexpression networks and identified a major module of genes with correlated gene expression that includes female-biased X genes and sexually dimorphic autosomal genes for which the sexual dimorphism is likely driven by the X genes. In this module, expression of X chromosome genes correlates with autosome genes, more than the expression of autosomal genes with each other. Our study identifies correlated patterns of autosomal and X-linked genes that are likely influenced by the sexual imbalance of X gene expression when X inactivation is inefficient.

Sex differences in activated corticotropin-releasing factor neurons within stress-related neurocircuitry and hypothalamic–pituitary–adrenocortical axis hormones following restraint in rats

Women may be more vulnerable to certain stress-related psychiatric illnesses than men due to differences in hypothalamic–pituitary–adrenocortical (HPA) axis function. To investigate potential sex differences in forebrain regions associated with HPA axis activation in rats, these experiments utilized acute exposure to a psychological stressor. Male and female rats in various stages of the estrous cycle were exposed to 30min of restraint, producing a robust HPA axis hormonal response in all animals, the magnitude of which was significantly higher in female rats. Although both male and female animals displayed equivalent c-fos expression in many brain regions known to be involved in the detection of threatening stimuli, three regions had significantly higher expression in females: the paraventricular nucleus of the hypothalamus (PVN), the anteroventral division of the bed nucleus of the stria terminalis (BSTav), and the medial preoptic area (MPOA). Dual fluorescence in situ hybridization analysis of neurons containing c-fos and corticotropin-releasing factor (CRF) mRNA in these regions revealed significantly more c-fos and CRF single-labeled neurons, as well as significantly more double-labeled neurons in females. Surprisingly, there was no effect of the estrous cycle on any measure analyzed, and an additional experiment revealed no demonstrable effect of estradiol replacement following ovariectomy on HPA axis hormone induction following stress. Taken together, these data suggest sex differences in HPA axis activation in response to perceived threat may be influenced by specific populations of CRF neurons in key stress-related brain regions, the BSTav, MPOA, and PVN, which may be independent of circulating sex steroids.