Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes (DMRT, VTG, GnRHR, FSHR, CYP1...Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes (DMRT, VTG, GnRHR, FSHR, CYP17A, CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations ofBisphenol A (BPA) and 17[3-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects orE2 as a model estrogen were stronger. Among the 7 genes, VTG, CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.展开更多
Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually rega...Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21-34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1,0±0.7 IU 1-1 vs 0.4±0.4 IU 1-1, P 〈 0.05) and stimulated LH (28.3 ± 22.6 IU 1-1 vs 1.9 ±1.1 IU 1-1, P 〈 0.01) levels, as well as larger testicle size (5.1 ±2.6 ml vs 1.5± 0.3 ml, P〈 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.展开更多
Peroxisome proliferator-activated receptor gamma (PPARy) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARy acts as an important molecule for regulating energy homeo...Peroxisome proliferator-activated receptor gamma (PPARy) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARy acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally regulated by HPG. In the human, PPARγprotein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells (spermatocytes). Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARy signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.展开更多
The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a la...The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone level<12 nmol l−1.Testicular volume was measured by orchidometer,testosterone by liquid chromatography/tandem mass spectrometry,and body composition by dual-energy X-ray absorptiometry.Men completed the Aging Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer testing.Eighty-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−1.Median testicular volume was 18(IQR:10,20)ml.Testicular volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and testosterone.When BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular volume.Testicular volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or AMS.In obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis action.From a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.展开更多
The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pit...The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.展开更多
One of the emerging hot topics in biosciences is the intriguing link between gut microbial communities and its influences outside the gastrointestinal tract, such as the central nervous system (CNS), including its cog...One of the emerging hot topics in biosciences is the intriguing link between gut microbial communities and its influences outside the gastrointestinal tract, such as the central nervous system (CNS), including its cognitive activities and immune responses. Beyond its neuroprotective properties, microglia are also critical for neuronal synaptic pruning and neural remodeling during CNS development. Prolonged microglia activation and neuroinflammation are considered key contributors to neurological disorders. In this regard, it is becoming increasingly important to consider the potential influences underlying the crosstalk between the intestinal microbiota ecosystem and host when determining biomarkers of disease and treatment efficacy. The commensal microbiota is critical for immune development and continuous function through the recognition of bacteria-produced and regulated metabolites. In cases of microbial dysbiosis and microglial dysfunction, chronic neuroinflammation may persist, leading to the propagation of neurological disorders. To address potential mechanisms, this review focuses on the microbiota-gut-brain axis as it relates to communication pathways that have been linked to aberrant CNS immune activity and pathology. We also address anti-inflammatory and neuroprotective mediators which may counteract these detrimental activities. Finally, we explore the potential benefits of current and novel microbiome-targeted approaches to treat neuroinflammation and consequential neurological disease.展开更多
基金Supported by the special funds for the Basic R&D Program in the Central Non-profit Research Institutes(No.2060302)
文摘Endocrine disrupting chemicals (EDCs) are increasingly viewed as persistent pollutants, similar to natural hormones in function. This paper describes the expression profiles of 7 genes (DMRT, VTG, GnRHR, FSHR, CYP17A, CYP19A, and CYP19B) involved in sex steroid synthesis and action as well as sexual development in adult male and female Cynoglossus semilaevis, after exposure to different concentrations ofBisphenol A (BPA) and 17[3-estradiol (E2). Both BPA (1, 10, 50, 125, and 250 mg/kg) and E2 (0.5, 5, and 10 mg/kg) induced changes in target gene expression, although the estrogenic effects orE2 as a model estrogen were stronger. Among the 7 genes, VTG, CYP17A and CYP19 responded strongly to BPA or E2 exposure and can thus serve as reference biomarkers for estrogenic EDCs exposure in marine teleosts. These data will provide a window to establish a hypothalamic-pituitary-gonadal model in C. semilaevis to better understand the effect pathways of EDCs.
文摘Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21-34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1,0±0.7 IU 1-1 vs 0.4±0.4 IU 1-1, P 〈 0.05) and stimulated LH (28.3 ± 22.6 IU 1-1 vs 1.9 ±1.1 IU 1-1, P 〈 0.01) levels, as well as larger testicle size (5.1 ±2.6 ml vs 1.5± 0.3 ml, P〈 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis.
文摘Peroxisome proliferator-activated receptor gamma (PPARy) is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARy acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal (HPG) axis, and is reciprocally regulated by HPG. In the human, PPARγprotein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells (spermatocytes). Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARy signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.
基金MNTF was supported an ESA-RACP research establishment fellowship and MG by a career Developm ent Fellow(1024139)from the NHM RCBayer Pharm a AG(Berlin,G erm any)provided testosterone,placebo and financial support to conduct investigation during the RCT phase.
文摘The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic–pituitary–testicular(HPT)axis function.This was a cross-sectional substudy of a larger randomized controlled trial including obese men,body mass index(BMI)≥30 kg m−2,with a total testosterone level<12 nmol l−1.Testicular volume was measured by orchidometer,testosterone by liquid chromatography/tandem mass spectrometry,and body composition by dual-energy X-ray absorptiometry.Men completed the Aging Males'Symptoms(AMS)score,International Index of Erectile Function-5(IIEF-5),physical function,and handgrip dynamometer testing.Eighty-nine men participated with a median(interquartile range[IQR])age of 53.1(47.6,59.2)years,BMI of 37.0(34.6,40.5)kg m−2,and a total testosterone of 7.0(6.1,7.9)nmol l−1.Median testicular volume was 18(IQR:10,20)ml.Testicular volume was negatively correlated with BMI(τ=−0.1952,P=0.010)and total fat mass(τ=−0.2115,P=0.005)independent of age and testosterone.When BMI,testosterone,sex hormone-binding globulin(SHBG),and luteinizing hormone(LH)were present in a multivariable model,only BMI(-0.38 ml change in testicular volume per 1 kg m-2BMI;95%CI:−0.74,−0.02;P=0.04)and LH(-0.92 ml change in testicular volume per 1 IU l-1 LH;95%CI:−1.75,−0.095;P=0.03)remained independent significant predictors of testicular volume.Testicular volume was positively correlated with IIEF-5(τ=0.2092,P=0.021),but not related to handgrip strength,physical function tests,or AMS.In obese men,testicular volume is inversely and independently associated with measures of adiposity,but not with most clinical or biochemical markers of HPT axis action.From a clinical perspective,this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men.
文摘The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.
文摘One of the emerging hot topics in biosciences is the intriguing link between gut microbial communities and its influences outside the gastrointestinal tract, such as the central nervous system (CNS), including its cognitive activities and immune responses. Beyond its neuroprotective properties, microglia are also critical for neuronal synaptic pruning and neural remodeling during CNS development. Prolonged microglia activation and neuroinflammation are considered key contributors to neurological disorders. In this regard, it is becoming increasingly important to consider the potential influences underlying the crosstalk between the intestinal microbiota ecosystem and host when determining biomarkers of disease and treatment efficacy. The commensal microbiota is critical for immune development and continuous function through the recognition of bacteria-produced and regulated metabolites. In cases of microbial dysbiosis and microglial dysfunction, chronic neuroinflammation may persist, leading to the propagation of neurological disorders. To address potential mechanisms, this review focuses on the microbiota-gut-brain axis as it relates to communication pathways that have been linked to aberrant CNS immune activity and pathology. We also address anti-inflammatory and neuroprotective mediators which may counteract these detrimental activities. Finally, we explore the potential benefits of current and novel microbiome-targeted approaches to treat neuroinflammation and consequential neurological disease.