Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

Flower development and sexual dimorphism in Vernicia montana

The mu oil tree(Vernicia montana Lour.) is a dioecious species, but the genetic mechanisms underlying its phenotypic sexual dimorphism are unclear. In this study, we determined two pivotal phases of sex differentiation of mu oil tree via morphological and histological analyses of unisexual flowers:(Ⅰ) differentiation of male or female primordia to produce staminate flowers(SFs) or transient hermaphrodite flowers(HFs),and(Ⅱ) complete abortion of stamens in transient HFs to generate pistillate flowers(PFs). A total of 1621 sex-biased genes were identified by comparative transcriptome analysis which exhibited elevated rates of protein evolution than unbiased genes. The female-biased genes were enriched in the production of defense compounds while male-biased genes were focused on the production of viable pollens. Transcriptomebased analysis revealed that the differentially expressed genes(DEGs) between PFs and SFs in phase Ⅰ involved in abscisic acid(ABA), auxin(AUX), cytokinin(CK), ethylene(ET), and gibberellin(GA) biosynthesis and signaling showed higher expression levels in males than in females in general, whereas the DEGs involved in jasmonic acid(JA) and salicylic acid(SA) pathways displayed opposite expression patterns. Moreover,differentially expressed endogenous ABA, AUX, GAs, JA, and SA exhibited consistent biased expression patterns with the DEGs by UPLC-MSbased analysis. Exogenous application of an anti-ethylene plant growth regulator could promote the development of stamens in PFs and generated HFs. Comparative transcriptomic and hormonal analyses of PFs and SFs in phase Ⅱ indicated an increase in ET concentration when abortion of stamens in PFs occurred. This study suggested that phytohormones play key roles in sex dimorphism and ET may determine the development of stamens in PFs of mu oil tree, which provides an insight into plant sex differentiation mechanisms.

Epidemiological Profile of Men Who Have Sex with Men: First Data about Male Sex Workers in Central African Republic (CAR)

Objectives: Sex work is not well documented among African men. The aim of this study was to describe the epidemiological profile of men who have sex with men (MSM) and eventually to determine the proportion of sex workers (SW) among them, as well as the proportion of MSM who have been victims of gender-based violence (GBV). Material and Methods: A cross-sectional study coordinated by the Direction de la Médecine du Travail was carried out at the headquarters of the association ALTERNATIVES in Bangui Bangui from July 1 to October 31, 2021. Consenting MSM present during the study period were systematically included. Sociodemographic variables, those relating to the future vision of the activity and to GBV were collected and analyzed using Epi-Info version 7 software. Results: Forty MSM with an average age of 23 years and mainly secondary education (75.0%) were included. The vast majority of MSM were unemployed (85.0%). 45.0% had been victims of GBV and wanted to stop working as an MSM (47.5%), and almost 2/3 (65.0%) would accept another income-generating activity in exchange for the MSM. Violence was sexual (32.5%), economic (22.5%), physical (20.0%), verbal (12.5%) and psychological (12.5%). Conclusion: The MSM were mainly young, poorly educated, unemployed, and almost half were victims of GBV. The desire to change MSM activity to another income-generating activity alongside that of MSM shows that many of them are SW, workers in the informal sector. This must be taken into account in prevention activities, even if the data needs to be confirmed on a much larger sample.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Silencing transformer and transformer-2 in Zeugodacus cucurbitae causes defective sex determination with inviability of most pseudomales

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae(Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Hard life for sons in the nest?Sex-dependent offspring mortality in Great Tits in urban and forest areas

Sex-biased mortality can occur in birds during development,for example due to sexual differences in energy requirement and/or environmental sensitivity,or the effects of sex hormones or sex differences in the expression of mutations linked to sex chromosomes.The extent of sex-bias in mortality may also be related to environmental conditions that influence offspring development and survival.Urban areas often provide poorer conditions for nestling development resulting in higher offspring mortality compared to natural areas,which may accelerate sex differences in offspring mortality in cities.To test this hypothesis,we examined the sex ratio of dead offspring in Great Tits(Parus major),using 427 samples of unhatched eggs and dead nestlings collected in two urban and two forest sites between 2013 and 2019.The ratio of males in the whole sample of dead offspring(56.9%)was significantly higher than expected by an 1:1 ratio,and the strongest sex biases were detected in urban areas(57.6%males)and in young nestlings(<14 days old,59.0%males).However,the sex ratios of dead offspring did not differ significantly among study sites and between offspring developmental stages.29.3%of unhatched eggs contained a visible embryo,and the proportion of embryo-containing unhatched eggs did not differ significantly between urban and forest study sites.These results suggest male-biased offspring mortality in Great Tits,and highlight the need of large datasets to detect subtle differences between habitats and developmental stages.

The interventional effect of Polygonatum cyrtonema Hua polysaccharide on atherosclerosis in mice of different sexes

In the present study,we investigated the intervention effects of a purified Polygonatum cyrtonema polysaccharide(PCP)on high-fat diet(HFD)-induced atherosclerosis in male and female LDLr-/-mice.Results showed that HFD caused severe dyslipidemia,atherosclerotic lesions,oxidative damages and inflammation in male and female mice,and these effects seemed to be more pronounced in males than in females.However,the above variations could be dose-dependently reversed by PCP treatment,and the intervention effects on males were greater than those on females.Nuclear factor kappa-B(NF-κB),mitogen-activated protein kinase(MAPKs)and protein kinase B(Akt)are 3 pivotal signaling pathways mediating the development of atherosclerosis.Consistently,PCP was also found to significantly decrease the phosphorylation of p65,p38,extracellular-regulated kinase 1/2(ERK1/2)and Akt,and increase the protein expression of inhibitor of NF-κB(IκB)in the aortas of male and female mice induced by HFD.Taken together,these findings indicated that PCP could be effective for the prevention of atherosclerosis,and the intervention effect of PCP on male mice was more obvious than that of female mice.

Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various factors.However,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent conclusions.AIM To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical surgery.METHODS We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic reconstruction.Specific anatomical points were carefully marked and measured using advanced 3D modeling software.To analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation analysis.RESULTS The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue parameters.Males demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal diameter.By contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat tissue.However,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal diameter.CONCLUSION The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue parameters.This study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical outcomes.Further research and utilization of these parameters could lead to enhanced surgical methods and patient care in laparoscopic rectal cancer radical surgery.

Keep in mind sex differences when prescribing psychotropic drugs

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Effect of TSH Suppression Therapy on Sex Hormone Levels after Thyroid Cancer Surgery

Objective:To analyze the effect of thyroid-stimulating hormone(TSH)suppression therapy on sex hormone levels in patients undergoing postoperative treatment for thyroid cancer.Methods:A total of 40 patients undergoing postoperative thyroid cancer treatment were selected for data analysis.TSH suppression therapy was implemented during the postoperative period.Patients were grouped according to the TSH level:TSH<0.1,0.1≤TSH<0.5,and TSH≥0.5.Results:Among male patients,there were no significant differences in sex hormone levels at different dosing times and TSH levels(P>0.05).For female patients,testosterone levels at different dosing times showed no significant differences under the same circumstances(P>0.05).The comparison of testosterone levels at different TSH levels over 5 years of TSH suppression therapy did not yield significant differences(P>0.05).However,the comparison of testosterone levels within 5 years of TSH suppression therapy yielded significant differences(P<0.05),with the lowest levels observed at 0.1≤TSH<0.5.Conclusion:The use of TSH suppression therapy in postoperative thyroid cancer treatment minimally affects sex hormone levels in male patients.However,it has a significant impact on female patients.Therefore,preoperative sex hormone testing is recommended,and postoperative monitoring should include regular sex hormone testing.

Sex effect on growth performance and marker-aided sex discrimination of seedlings of Populus deltoides

Sex has a significant effect on various traits among dioecious plants.In this analysis of the sex effect on the radial growth and wood density of numerous 20-yearold trees of Populus deltoides growing in a common garden,male trees performed better than the females in radial growth,but sex did not significantly affect wood density.Growth rate and wood density were weakly negatively correlated.Sex selection is also critical for controlling seed-hair pollution from P.deltoides plantations.However,because the juvenile period of P.deltoides lasts for years,a reliable technique to determine the sex of juveniles has been needed.Here we developed a marker-aided technique to discriminate the sexes of P.deltoides seedlings.This study provides essential information on target traits and a highly desirable genetic toolkit for accelerate breeding programs for this important tree species.

Maleness-on-the-Y(MoY) orthologue is a key regulator of male sex determination in Zeugodacus cucurbitae(Diptera:Tephritidae)

The initiation of sex differentiation in insects is regulated by primary sex determination signals.In the Medfly Ceratitis capitata and other tephritids,Maleness-on-the-Y(MoY) is the master gene for male sex determination.However,the primary signal in Zeugodacus cucurbitae(Coquillett),a very destructive tephritid pest across the world,remains ambiguous.In this study,we have isolated and characterized the Medfly MoY homolog in Z.cucurbitae,ZcMoY.ZcMOY protein shows high sequence conservation to its homologs in Bactrocera species.ZcMoY transcription begins and peaks at very early embryonic stages and then becomes undetectable except the testes and heads of day 1 male adults.Silencing ZcMoY in early embryos by RNAi causes abnormal external genitalia and interior reproductive organs,giving rise to intersexes and feminization of XY individuals.The expression pattern and knockdown phenotypes of ZcMoY indicate that ZcMoY plays a key role in regulating sex determination of Z.cucurbitae males.Our findings will help the understanding of sex determination in Z.cucurbitae and facilitate the development of genetic sexing strains in its biological control.

Development of a high-efficiency sex pheromone formula to control Euproctis pseudoconspersa

The tea tussock moth(Euproctis pseudoconspersa)is one of the most destructive chewing pests in tea plantations and causes a serious allergic reaction on the skin of tea plantation workers.The sex pheromone components of its Japanese population were first identified as 10,14-dimethylpentadecyl isobutyrate(10Me14Me-15:iBu)and 14-methylpentadecyl isobutyrate(14Me-15:iBu),with a stereogenic center.Only 10Me14Me-15:iBu has been identified in the Chinese E.pseudoconspersa population.However,field tests have shown that 10Me14Me-15:iBu cannot meet the demand of effective pest control in China.To develop a high-efficiency E.pseudoconspersa sex pheromone formula,electroantennogram(EAG)recordings of(S)-and(R)-enantiomers of 10Me14Me-15:iBu and 14Me-15:iBu were obtained in the present study.The results demonstrated that the EAG responses of male antennae to(R)-enantiomers were significantly higher than responses to the(S)-enantiomers,and 14Me-15:iBu also elicited EAG activity.Field tests showed that the catch numbers of male moths by(R)-enantiomers were significantly higher(P<0.05)than those of(S)-enantiomers.Addition of 14Me-15:iBu significantly increased the catch numbers of both the(S)-and(R)-enantiomers.The efficient pheromone formula containing 0.75 mg(R)-10Me14Me-15:iBu and 0.1 mg 14Me-15:iBu showed significantly higher attractiveness than commercial pheromone products.Our study demonstrated that(R)-10Me14Me-15:iBu was the major sex pheromone component of E.pseudoconspersa,and 14Me-15:iBu might be the minor sex pheromone component.Furthermore,a high-efficiency sex pheromone formula for E.pseudoconspersa control was defined in this study.

Analysis of sex pheromone production and field trapping of the Asian corn borer(Ostrinia furnacalis Guenée)in Xinjiang,China

Identifying the sex pheromone systems of local pest populations facilitates their management,especially for moth species that show significant geographic variation in sex pheromone communication.We investigated the pheromone production and behavioral responses of the Asian corn borer(Ostrinia furnacalis Guenée;ACB)in Xinjiang,China.The ACB produces three compounds:(Z)-12-tetradecenyl acetate(Z12-14:Ac)and(E)-12-tetradecenyl acetate(E12-14:Ac)which are two sex pheromone compounds,and n-tetradecyl acetate(14:Ac)which has variable roles in mediating behavioral responses.The ratios of these three compounds produced in female gland are geographically distinct among different populations.Quantitative analysis of pheromone production showed that the proportions of Z12-14:Ac in the E/Z isomers(i.e.,Z and E12-14:Ac)and the proportions of 14:Ac in the ternary blend respectively averaged 60.46%(SD=5.26)and 25.00%(SD=7.37),with their probabilities normally or near-normally distributed.Trapping experiments in a cornfield indicated that deploying the E/Z isomers and the three compounds in rubber septa close to their gland ratios yielded the most captured males,while other ratios that deviated from the gland ratios showed reduced field captures.The ternary blend was significantly more attractive to males than the E/Z isomers in the field,indicating a functional role of 14:Ac as the third pheromone component used by the local population.Additionally,the dose-response test demonstrated that the application of the three compounds at dosages between 200 and 350μg attracted significantly more males compared to other dosages.Therefore,the characterization of this local ACB pheromone system provides additional information about its geographic variation and serves as a basis for optimizing the pheromone-mediated control of this pest in Xinjiang.

Sex dimorphism and metabolic profiles in management of metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease(MAFLD)refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide.Although metabolism is highly influenced by the effects of sex hormones,studies of sex differences in the incidence and progression of MAFLD are scarce.Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms.First,metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time.Second,metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers.Some studies demonstrate associations between circulating metabolites and early and established MAFLD,but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management.In this review,we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD,the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers,and how this evidence may help in the future management of the disease.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Expression of Sex-Related Genes in Chicken Embryos During Male-to-Female Sex Reversal Exposure to Diethylstilbestrol

Sex emerges out of a delicate dance between a variety of promale, anti-male, and possibly profemale genes. To investigate the role that sex-related genes play in sex determination and gonadal differentiation of fowl, we constructed a male-to- female sex-reversal model of chick induced by diethylstilbestrol （DES） at onset of incubation （E0）. The results of semi- quantitative PCR showed that the expression of Sf1, the orphan nuclear receptor steroidogenic factor-1 gene, was put forward from E7d to E5d and up-regulated during E5-7d; the Dmrt1, the double sex and the Mab-3 related to transcription factor 1 gene, was down-regulated during E3-7d. Meanwhile, anti-Müllerian hormone gene （Amh） expressed at a similar level in the genetic females and sex-reversal females before E7d, while no expression products of the three female-specific genes Wpkci, Fet1 and Foxl2 were detected in male-to-female embryos. These findings suggest that the expression of some certain sex-related genes, induced by the exogenous estrogen during period of sex determination and gonadal differentiation, results in the male-to-female sex reversal. Moreover, high activity of Sf1 gene during E5-7d might be related to the profemale process, while low activity of Dmrt1 gene during E3-5d might be anti-male. The expression activity of Amh gene might only contribute to the promale process after E7d, however, it is possibly not an anti-female gene in chick embryos.

Eccentric exercise-induced muscle weakness abolishes sex differences in fatigability during sustained submaximal isometric contractions

Background:Females are typically less fatigable than males during sustained isometric contractions at lower isometric contraction intensities.This sex difference in fatigability becomes more variable during higher intensity isometric and dynamic contractions.While less fatiguing than isometric or concentric contractions,eccentric contractions induce greater and longer lasting impairments in force production.However,it is not clear how muscle weakness influences fatigability in males and females during sustained isometric contractions.Methods:We investigated the effects of eccentric exercise-induced muscle weakness on time to task failure(TTF)during a sustained submaximal isometric contraction in young(18-30 years)healthy males(n=9)and females(n=10).Participants performed a sustained isometric contraction of the dorsiflexors at 35°plantar flexion by matching a 30%maximal voluntary contraction(MVC)torque target until task failure(i.e.,falling below 5%of their target torque for>2 s).The same sustained isometric contraction was repeated 30 min after 150 maximal eccentric contractions.Agonist and antagonist activation were assessed using surface electromyography over the tibialis anterior and soleus muscles,respectively.Results:Males were~41%stronger than females.Following eccentric exercise both males and females experienced an~20%decline in maximal voliuntary contraction torque.TTF was-34%longer in females than males prior to eccentic exercise-induced muscle weakness.However,following eccentric exercise-induced muscle weakness,this sex-related difference was abolished,with both groups having an"45%shorter TTF.Notably,there was~100%greater antagonist activation in the female group during the sustained isometric contraction following exercise-induced weakness as compared to the males.Conclusion:This increase in antagonist activation disadvantaged females by decreasing their TTF,resulting in a blunting of their typical fatigability advantage over males.