The expression of Hoxa10 and its regulation by sex steroids andHB-EGF at the time of implantation in the human endometrium

Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.

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.

Sex steroids of black scabbardfish,Aphanopus carbo,in relation to reproductive and migratory dynamics

Black scabbardfish,Aphanopus carbo,is a commercially important species that takes distant migrations throughout its life cycle.Sex steroids were measured by radioimmunoassay in the blood plasma of specimens caught off the Madeira Archipelago and mainland Portugal to link this species migratory path with its reproductive cycle.Furthermore,a pilot study using Mozambique tilapia(Oreochromis mossambicus)was designed to evaluate the effect of sample freshness on steroid levels because black scabbardfish blood was collected at separate times after specimens were caught.The changes in T and 11-KT concentrations between the time of blood extraction and the time after preservation did not statistically differ among the different methods applied.Therefore,measured black scabbardfish steroid concentrations were directly used in the subsequent data analyses.In females,E2 and in T concentrations peaked at a late stage of vitellogenesis.E2 concentration was significantly different between females caught off each area.Clustering E2 and T concentrations from all developing females resulted in the separation of two distinct groups,independently of their geographical area.In males,T and 11-KT were not significantly different between maturity stages.The hepatosomatic index of males caught off mainland Portugal was relatively high.This may reflect a mechanism for storing energy that will later be consumed during migration to the spawning grounds.The trend of sex steroids concentrations throughout the sexual maturation of the species is consistent with the morphological indicators and shows evidence of the reproductive and migratory pattern hypothesised for the black scabbardfish in NE Atlantic.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Hydroxylation and sulfation of sex steroid hormones in inflammatory liver

Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450,glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, and O-methylation by catechol Omethyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic inflammatory response in vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N mice were induced with hepatic inflammation by diethylnitrosamine(DEN) exposure. We observed upregulation of Cyp19a1, Hsd17b1, Cyplal, Sult1e1 in the DEN-treated livers compared to the control-treated livers using real time PCR. Moreover, the increased Cyp19a1 and Hsd17b1 levels support the possibility that estrogen biosynthesis from androgens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyp1a1 and Cyp1b1 in the hydroxylation of estrogen facilitated the conversion of estrogen to 2-or 4-hydroxyestrogen,respectively. In addition, the substantial increase in the Sultlel enzyme levels could lead to sulfate conjugation of hydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfate conjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to their receptors in the whole body.

Study on two steroidal sex hormones in rice

Steroidal sex hormones including androgensand estrogens are important in the reproduc-tive development of mammals. A number ofstudies suggested that these steroids mighthave similar functions in plants. A latest re-search on Nongken 58s, a photoperiod-sensi-tire genie male-sterile rice (PGMR), showed

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Successful Production of an All-Female Common Carp (Cyprinus carpio L.) Population Using cyp17a1-Deficient Neomale Carp

Due to sexual dimorphism in the growth of certain cultured fish species,the production of monosex fishes is desirable for the aquaculture industry.Nowadays,the most widely practiced technique available for the mass production of monosex fish populations is sex steroid-induced sex reversal.Here,a novel strategy for the successful production of all-female(AF)common carp(Cyprinus carpio L.),to take advantage of the sexual dimorphism in growth documented in this species,has been developed using genetic engineering via single gene-targeting manipulation without any exogenous hormone treatments.Male and female heterozygous cyp17a1-deficient common carp were first obtained using the clustered regularly interspaced short palindromic repeats/CRISPR-associated endonuclease 9(CRISPR/Cas9)technique.An all-male phenotype for homozygous cyp17a1-deficient carp,regardless of the individuals’sexdetermination genotypes(XY or XX),has been observed.A male-specific DNA marker newly identified in our laboratory was used to screen the neomale carp population with the XX genotype from the cyp17a1-deficient carp.These neomale carp develop a normal testis structure with normal spermatogenesis and sperm capacity.The neomale common carp were then mated with wild-type(WT)females(cyp17a1^(+/+)XX genotype)using artificial fertilization.All the AF offspring sample fish from the neomale-WT female mating were confirmed as having the cyp17a^(1+/-)XX genotype,and normal development of gonads to ovaries was observed in 100.00%of this group at eight months post-fertilization(mpf).A total of 1000 carp fingerlings,500 from the WT male and female and 500 from the neomale and WT female mating,were mixed and reared in the same pond.The average body weight of cyp17a1^(+/-)XX females was higher by 6.60%(8 mpf)and 32.66%(12 mpf)than that of the control common carp.Our study demonstrates the first successful production of a monosex teleost population with the advantages of sexual dimorphism in growth using genetic manipulation targeting a single locus.

Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents

In the recent decades,obesity rates among children and adolescents,especially males,have increased significantly.This worldwide phenomenon is thought to significantly affect the levels of sex hormones.However,the association between waist circumference(a marker of abdominal obesity)and sex hormone levels in children and adolescents is unknown.In this study,4031 participants aged 6–19 years from the United States National Health and Nutrition Examination Survey(NHANES)in the USA were enrolled in this study.The common confounders of age,race,body mass index,educational level,family income,diabetes,and time of sample collection were also collected.The participants missing any of the above information were excluded from the study.We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone,estradiol,sex hormone-binding globulin(SHBG),free androgen index(FAI),and testosterone/estradiol ratio(T/E2).Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates.As waist circumference increases,testosterone levels in children and adolescents show an overall decline after a brief increase,with the inflection point for waist circumference of 65–66 cm.In addition,waist circumference positively correlates with estradiol levels in male children(β=0.007,95%confidence interval:0.004–0.009).Moreover,circulating SHBG decreases in children and adolescents as waist circumference increases.In conclusion,this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

Sexual plasticity in bony fishes:Analyzing morphological to molecular changes of sex reversal

Sex reversal is one of the characteristic properties of sexual plasticity in bony fishes wherein both natural and induced sex change happens at various stages of life cycle in different species.Sex determination in gonochoristic species is genetically regulated,wherein the same sex is retained throughout their life span whereas hermaphrodites change their sex during development or adulthood.In sequential hermaphrodites,serial sex change occurs at different points of life cycle.Concurrently,synchronous hermaphrodites function as both the sexes during spawning.Other variables like temperature,pH and social factors can trigger sex reversal in teleost.Sex reversal through gene mutations and chemicals/hormones,including sex steroids,can be induced mostly at early developmental stages but natural sex reversal can occur at any time.Sex reversal mechanism shows morphological to molecular changes,which are ideal for identification of sex-specific gene markers.In fact,gonadal transdifferentiation occurs at the molecular level through differential expression of transcription factors and steroidogenic enzyme genes vis-a-vis hormones,thereby imparting phenotypic or structural changes.In addition,brain shows sexual dimorphism which is mostly consequential to gonadal sex development and occasionally either causative.The major breakthrough in this line is the identification of sex determining genes such as dmy/dmrt1Yb,gsdfY,sox3 in the Japanese medaka and amhY in Patagonian pejerrey.Incidentally,the induction of mono-sex population by favouring one sex due to sex-specific differences in growth is an important economic boom for aquaculture.This review comprehensively highlights key molecular factors involved in natural and induced sex reversal conditions to illustrate teleostean sexual plasticity and its application perspectives.

Isolation and characterization of a bacterial strain that efficiently degrades sex steroid hormones

A bacterial strain,ZY3,growing on sex steroid hormones as the sole source of carbon and energy was isolated from the sewage treatment plant of a prophylactic steroids factory.ZY3 degrades the 3-methoxy-17b-hydroxy-1,3,5(10),8(9)-d-4-estren(MHE).This strain was preli-minarily identified as Raoultella sp.ZY3 according to its morphology and its 16S rRNA gene sequence.During the experimental period(72 h),the optimum temperature,pH and 3-MHE concentration for the degradation of hydride by the strain ZY3 were 35°C,10 and 10 mg/L,respectively.The degradation rate of the sex steroid hormones increased to 87%and 85% after the addition of maltose and peptone,respectively.

Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone(T)and sex hormone-binding globulin(SHBG)levels.Several mechanisms for this have been proposed,but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization,this study investigates whether severity and histological components of nonalcoholic fatty liver disease(NAFLD)are associated with sex steroid levels in obese men.This cross-sectional study included 80 obese men(age:46±11 years;body mass index:42.2±5.5 kg m^-2).Serum levels of total T and estradiol(E.)were measured using liquid chromatography coupled with tandem mass spectroscopy(LC/MS-MS)and SHBG and gonadotropins by immunoassay.Liver biopsies were evaluated using Steatosis.Activity,and Fibrosis scoring.Participants with steatohepatitis had similar median(1st quartile-3rd quartile)total T levels(7.6[5.0-11.0]nmol l^-1 vs 8.2[7.2-10.9]nmol l^-1;P=0.147),lower calculated free T(cFT)levels(148.9[122.9-188.8]pmol 1-1 s 199.5[157.3-237.6] pmol l^-1;P=0.006),and higher free E.T ratios(10.0[6.4-13.9]×10^-3 vs 7.1[5.7-10.7]×10^-3;P=0.026)compared to men with only nonalcoholic fatty liver.Among the histological components of NAFLD.only steatosis was independently associated with total T(r=-0.331.P=0.003)and cFT levels(r=-0.255.P=0.025).Obese men with.steatohepatitis have even lower cFT levels compared to those without,an association mainly driven by grade of steatosis.Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.

Adaptive hearing in the vocal plainfin midshipman fish:getting in tune for the breeding season and implications for acoustic communication

The plainfin midshipman fish(Porichthys notatus Girard,1854)is a vocal species of batrachoidid fish that gen-erates acoustic signals for intraspecific communication during social and reproductive activity and has become a good model for investigating the neural and endocrine mechanisms of vocal-acoustic communication.Reproduc-tively active female plainfin midshipman fish use their auditory sense to detect and locate“singing”males,which produce a multiharmonic advertisement call to attract females for spawning.The seasonal onset of male adver-tisement calling in the midshipman fish coincides with an increase in the range of frequency sensitivity of the female’s inner ear saccule,the main organ of hearing,thus leading to enhanced encoding of the dominant frequency components of male advertisement calls.Non-reproductive females treated with either testosterone or 17β-estradiol exhibit a dramatic increase in the inner ear’s frequency sensitivity that mimics the reproductive fe-male’s auditory phenotype and leads to an increased detection of the male’s advertisement call.This novel form of auditory plasticity provides an adaptable mechanism that enhances coupling between sender and receiver in vocal communication.This review focuses on recent evidence for seasonal reproductive-state and steroid-dependent plasticity of auditory frequency sensitivity in the peripheral auditory system of the midshipman fish.The potential steroid-dependent mechanism(s)that lead to this novel form of auditory and behavioral plasticity are also dis-cussed.

Hypothalamic-Pituitary-End-Organ Axes:Hormone Function in Female Patients with Major Depressive Disorder

Classic hypothalamic-pituitary-end-organ feedback loops–the hypothalamic-pituitary-adrenal axis(HPAA),hypothalamic-pituitary-thyroidal axis(HPTA),and hypothalamic-pituitary-gonadal axis(HPGA)–are associated with the neuroendocrine and immune systems in major depressive disorder(MDD).Female patients with MDD present with evident neuroendocrine and immunological changes.Glucocorticoid,thyroid hormone,and reproductive steroid levels fluctuate with menstrual cycles,which might lead to glucocorticoid receptor resistance,impairment of triiodothyronine conversion,and sex hormone secretion disorders.In this review,we summarize the independent and interactive functions of these three axes in female MDD patients.The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level,especially when considering the HPAA and HPGA.