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1.
Gene ; 740: 144535, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32156529

RESUMO

Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways.


Assuntos
Compostos Benzidrílicos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Fenóis , Maturidade Sexual/efeitos dos fármacos , Animais , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Estrogênios/sangue , Estrogênios/metabolismo , Feminino , Perfilação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Ovário/ultraestrutura , Fenóis/sangue , Fenóis/metabolismo , Fenóis/toxicidade
2.
Environ Pollut ; 256: 112957, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672375

RESUMO

Parabens are class of preservatives used in vast majority of commercial products, and a potential Endocrine Disrupting Chemical (EDC). The present study was undertaken to delineate the effects of n-butylparaben on F1 male progeny exposed maternally through gestation and lactation via subcutaneous route. The F0 dams were given subcutaneous injections of n-butylparaben from gestation day (GD) 6 to postnatal day (PND) 21 with doses of 10, 100, 1000 mg/kg Bw/day in corn oil. The F1 male rats were monitored for pubertal development and sexual maturation; these were sacrificed on PND 30, 45 and 75. On PND 75, these F1 male rats were subjected for fertility assessment with unexposed female rats. A delayed testicular descent at 100 and 1000 mg/kg Bw dose and delayed preputial separation at 10 mg/kg Bw dose was observed in exposed F1 male rats. Decreased sperm count, motility and Daily Sperm Production was observed at 100 mg/kg Bw dose at PND 75. Interestingly, the sperm transit time in the epididymis was accelerated at this dose. Significant perturbed testicular expression of steroid receptors (ERα and ß, AR), INSL3 and StAR genes with increased T and LH levels indicates direct effect on spermatogenesis and steroidogenesis. These F1 generation adult rats were sub-fertile with increased (%) pre- and post-implantation loss at 100 and 1000 mg/kg Bw/day dose. This is the first report on n-butylparaben highlighting the involvement of testicular leydig cells with accelerated sperm transit time leading to reduced fertility in the maternally exposed F1 male rats through estrogenic/anti-androgenic action.


Assuntos
Disruptores Endócrinos/toxicidade , Fertilidade/efeitos dos fármacos , Parabenos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Receptores de Esteroides/metabolismo , Espermatogênese/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lactação , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Receptores de Esteroides/genética , Maturidade Sexual/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/crescimento & desenvolvimento
3.
Toxicol Lett ; 319: 1-10, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689472

RESUMO

Chlorocholine chloride (CCC), a plant growth retardant, may act as an endocrine disruptor. Our previous study showed that pubertal CCC exposure in rats might decrease testosterone (T) synthesis. This study observed the changes in pubertal development and reproduction of male rats exposed to CCC and its underlying mechanisms. Rats were exposed to CCC (0, 75, 137.5 and 200 mg/kg bw/day) from postnatal day 23 to 60. The results showed that CCC treatment delayed the onset of puberty and reduced the relative organ weight of prostate. Seminiferous tubules with deciduous spermatogenic cells were observed in the 200 mg/kg bw/day group. Sexual behavior was inhibited in the 137.5 and 200 mg/kg bw/day groups. Sperm motility, litter size and normalized anogenital distance (AGD) of male pups were decreased in the 137.5 and 200 mg/kg bw/day groups. Serum kisspeptin level and serum and testicular levels of T were reduced in all CCC treated groups. Crucial hormones in hypothalamic-pituitary-testicular (HPT) axis were reduced subsequently after CCC treatment. Collectively, our results demonstrated that CCC might disturb HPT axis through suppressing the secretion of kisspeptin and subsequently lead to delayed puberty onset and impaired reproductive functions.


Assuntos
Clormequat/toxicidade , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Genitália/anatomia & histologia , Genitália/efeitos dos fármacos , Genitália/crescimento & desenvolvimento , Hormônios Esteroides Gonadais/sangue , Kisspeptinas/metabolismo , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Ratos , Ratos Sprague-Dawley , Túbulos Seminíferos/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/sangue
4.
Protein Expr Purif ; 166: 105510, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31628987

RESUMO

GnRH is a neuropeptide known to regulate reproduction in vertebrates. The purpose of this study was to design and produce recombinant gonadotropin-releasing hormone associated peptide (rGnRH/GAP) as an alternative of the previous GnRHs and native extracted hormone from tissue, to induce final maturation in fish. Decapeptide as well as GAP area sequences were compared between GnRH1, GnRH2, and mGnRH from Acipenser sp and Huso huso, respectively. Considering the conserved amino acids and the replacement of un-stable amino acids with those that were more stable against proteolytic digestion as well as had a longer half-life, the sequence was designed. The sequences of decapeptide and GAP region were synthesized and then cloned on pET28a expression vector and transformed into expression host Escherichia coli BL21(DE3). The supernatant of cultured recombinant bacteria was used for purification using TALON Metal affinity resin. The purity of the GnRH/GAP was confirmed by single 8 kDa band on SDS-PAGE and Western blot. Bioinformatics studies were performed for evaluation of homology between GnRH protein sequences and prediction of 3D protein structure using Swiss Model. The result showed that the structure prediction of the recombinant GnRH decapeptide was relatively similar to decapeptide of GnRH2 from Beluga (Huso huso). The GAP structure was similar to GAP1 of Nile tilapia (Oreochromis niloticus) and sturgeon and GnRH2 of Chinese sturgeon (Acipenser sinensis). The mass analysis showed that the sequence was exactly the same as designated sequence. Biology activity of rGnRH/GAP was tested in mature goldfish (Carassius auratus) and results showed that rGnRH/GAP had a positive effect in final maturation. Indeed 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) was increased 17 h and 24 h after injection with rGnRH/GAP and spawning stemmed from that injection. These novel findings introduce the potential of utilizing rGnRH/GAP in aquaculture.


Assuntos
Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/genética , Oligopeptídeos/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Sequência de Aminoácidos , Animais , Cromatografia de Afinidade , Clonagem Molecular , Escherichia coli/genética , Peixes , Vetores Genéticos , Estabilidade Proteica , Maturidade Sexual/efeitos dos fármacos
5.
Ecotoxicol Environ Saf ; 188: 109898, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31711775

RESUMO

Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABAA receptor (GABAAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats. First, female rats received daily dose of MnCl2 0 (saline), 2.5, 5 and 10 mg/kg b.w by oral gavage during postnatal day (PND) 21-32. Animals administered with 10 mg/kg MnCl2 exhibited earlier puberty onset age and advanced ovary and uterus development than these in saline-treatment group. Furthermore, we found that decrease of GABAAR result in elevated production of nitric oxide synthase1 (NOS1), NO and GnRH in the POA-AH. Second, we recorded the neuronal spikes alternation after perfusion with GABAAR inhibitor bicuculline (BIC), GABAAR agonist isoguvacine (isog), and MnCl2 from the POA-AH in acute brain slices of PND21 rats. Spontaneous firing revealed a powerful GABAAR-mediated action on immature POA-AH and confirm that MnCl2 has a significant effect on GABAAR. Third, we revealed that decrease in NOS1 and NO production by treatment with isog-alone or isog+MnCl2 contribute to the decrease of GnRH in the POA-AH and a delayed puberty onset age compared to treatment with MnCl2-alone. Together, these results suggested that excessive exposure to MnCl2 stimulates NO production through decreased GABAAR in the POA-AH to advance puberty onset in immature female rats.


Assuntos
Envelhecimento/efeitos dos fármacos , Cloretos/toxicidade , Disruptores Endócrinos/toxicidade , Óxido Nítrico/metabolismo , Área Pré-Óptica/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Maturidade Sexual/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Compostos de Manganês , Neurônios/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Área Pré-Óptica/crescimento & desenvolvimento , Área Pré-Óptica/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Útero/diagnóstico por imagem , Útero/efeitos dos fármacos , Desmame
6.
J Anim Sci ; 97(10): 4334-4340, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31504639

RESUMO

Brassica carinata is a new oilseed crop in Florida with the potential of producing high-quality jet biofuel. A high-protein meal (~40% crude protein; CP) is obtained as a byproduct of oil extraction; however, limited research is available on the utilization of this meal as a protein supplement for beef cattle. A generalized randomized block design was used to evaluate the effects of supplementation with B. carinata meal pellets on performance and attainment of puberty in growing beef heifers consuming bermudagrass hay (Cynodon dactylon) ad libitum. Sixty-four Angus crossbred heifers (240 ± 39 kg initial body weight; BW) were stratified and blocked (2 blocks: light and heavy) by initial BW and randomly allocated into 18 pens over 2 consecutive years (10 in year 1 and 8 in year 2). Within block, pens were randomly assigned to 1 of 2 treatments: 0 (CTL) or 0.3% of BW/d (as fed) of B. carinata meal pellets (BCM). Blood samples and BW were collected weekly for 70 d, before daily supplementation. Data were analyzed using PROC MIXED of SAS with repeated measures. Model included the fixed effects of treatment, day, treatment × day interactions, block, and block × treatment interactions, with the random effect of year. Plasma was analyzed for concentrations of progesterone, triiodothyronine (T3), thyroxine (T4), ceruloplasmin (Cp), and haptoglobin (Hp). An effect of treatment was observed (P ˂ 0.01) for ADG between CTL (0.14 kg) and BCM (0.42 kg). There was no treatment or block (P > 0.05) effect for concentrations of T3, T4, or Hp; however, there was an effect of day (P < 0.01) for T3, T4, and Cp. An effect of treatment (P ˂ 0.01) was observed for Cp, with CTL having greater concentrations compared with BCM. Time to attainment of puberty did not differ (P = 0.93) between treatments. Feeding B. carinata meal as a protein supplement at 0.3% of BW/d is a viable option for increasing ADG of growing beef heifers, without affecting attainment of puberty, thyroid hormone status, or eliciting an acute phase response.


Assuntos
Brassica , Bovinos/fisiologia , Proteínas na Dieta/farmacologia , Suplementos Nutricionais/análise , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Cynodon , Dieta/veterinária , Feminino , Progesterona/sangue , Distribuição Aleatória , Maturidade Sexual/efeitos dos fármacos
7.
Sci Total Environ ; 686: 1229-1237, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31412519

RESUMO

Underground drinking water is commonly contaminated with arsenite (As) and fluoride (F) associated with chronic kidney diseases in humans; however, the combined renal toxicity of these pollutants and the underlying mechanisms are still unclear. The aim of the present study was to investigate the interaction between As and F regarding toxic effects on the kidney of rat offspring exposed to pollutants during prenatal and postnatal development. Pregnant rats were randomly divided into four groups that received NaAsO2 (50 mg/L), NaF (100 mg/L), NaAsO2 (50 mg/L) and NaF (100 mg/L) in drinking water, or clean water, respectively, during gestation and lactation. After weaning, six male pups were randomly selected from each group and continued on the same treatment as their mothers for up to three months. The results revealed that subchronic exposure to high-dose As and/or F decreased the organ coefficient of the kidneys and disrupted kidney ultrastructure, moreover inhibited the activity of antioxidant enzymes and increased the generation of malondialdehyde in the kidney. As exposure alone or combined with F led to an upregulation of nuclear factor erythroid 2-related factor-2 (Nrf2) and its regulatory targets (Ho-1, Gclc, and Nqo1), whereas the effect of F alone was not significant. These results suggest that the renal toxicity of As and F is associated with the induction of mitochondrial damage and oxidative stress, and alters the expression of Nrf2 and its regulatory targets. Furthermore, variance analysis results showed that an interaction between As and F in the toxicity process.


Assuntos
Arsenitos/efeitos adversos , Fluoretos/efeitos adversos , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Feminino , Rim/ultraestrutura , Masculino , Exposição Materna/efeitos adversos , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Subcrônica
8.
Exp Neurol ; 321: 113039, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31442443

RESUMO

Neonatal hypoxic-ischemic brain damage (HIBD) survivors present with long-term neurological disorders affecting their quality of life, and there remains a lack of effective treatment. Toll-like receptor 4 (TLR4) is widely distributed in nerve cells and its inhibition has a neuroprotective effect against brain injury. The present study aimed to evaluate the long-term neuroprotective effects of early inhibition of TLR4 during HIBD. Seven-day-old rat pups were subjected to left carotid artery ligation followed by 2 h of hypoxia (8.0% O2). A single dose of TAK-242 (0.5 mg/kg), a TLR4-specific antagonist, was intraperitoneally injected half an hour prior to hypoxic ischemia (HI). The long-term effects of TAK-242 inhibition on the induced hippocampal injury were investigated by assessing behaviour at P28, and then using a variety of methods to exploring the mechanism, including immunofluorescence, Golgi silver staining, Western blotting and real-time polymerase chain reaction (RT-PCR). TAK-242 treatment significantly reduced the expression levels of TLR4 and its downstream signalling molecules in the ipsilateral lesion of the hippocampus 24 h after HIBD. The Morris water maze (MWM) test demonstrated that TAK-242 treatment reduced the loss of HI-induced learning and memory functions. Immunofluorescence experiments showed that TAK-242 administration attenuated HI-induced loss of neurons, prevented the activation of microglia and astrocytes, and increased the expression of the glutamate receptor subtype, N-methyl d-aspartate 2A (NR2A) in the ipsilateral hippocampus region. Golgi silver staining revealed that TAK-242 prevented an HI-induced decline in spine density in the ipsilateral hippocampus. Western blot and RT-PCR results indicated that the expression of NR2A protein and mRNA in the ipsilateral hippocampi of adolescent rats decreased after neonatal HIBD; early TAK-242 administration may reverse these effects. In conclusion, our findings indicate that early inhibition of TLR4 signalling may improve the long-term prognosis of neonatal HIBD. The mechanisms contributing to this improvement involve reductions in neuronal loss, a decrease in glial cell activation, and an improvement in synaptic plasticity.


Assuntos
Hipocampo/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Plasticidade Neuronal/fisiologia , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Hipóxia-Isquemia Encefálica/complicações , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/efeitos dos fármacos , Sulfonamidas/farmacologia
9.
BMC Endocr Disord ; 19(1): 72, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296213

RESUMO

BACKGROUND: Further knowledge about the pubertal development mode of girls with Turner syndrome (TS) who have undergone hormone replacement therapy (HRT) is beneficial to the proposal of an optimal HRT regimen. This study examined the pubertal development mode of girls with TS who underwent HRT and evaluated the characteristics of optimal sex induction therapy in girls with TS. METHOD: We conducted a retrospective, longitudinal study over the past two decades at The First Affiliated Hospital, Sun Yat-sen University. PATIENTS: Seventy-one patients with TS and two groups of normal Chinese girls. RESULTS: The total investigation time was 3.00 (2.00, 4.66) years. The interval of each stage was significantly longer (P < 0.001) in the girls with TS than that in the normal Chinese girls, except for B2-3 (P = 0.011). The uterine volumes of the girls with TS in stages B2 and 3 were greater than those of the control group (P = 0.046), whereas the uterine volume of the control group was inversely greater than that of the TS group among those who reached stages B4 and 5 (P = 0.034). During HRT, the uterine volume grew significantly from all previous stages except for breast stage 5 (B3 vs.2: Z = - 2.031; P = 0.042; B4 vs. 3: Z = - 2.273; P = 0.023; B5 vs. 4: Z = - 1.368; P = 0.171). The paired data of 27 girls with TS showed that the uterine volume (17.93 ± 9.31 ml vs. 13.75 ± 6.67 ml) and width (2.54 ± 0.66 cm vs. 2.22 ± 0.36 cm) increased significantly during artificial cycles compared with before artificial cycles (t = - 2.79 and - 2.51, P = 0.01 and 0.018). CONCLUSION: HRT led to normal breast development in girls with TS; half of the girls with TS in our study reached Tanner stage B5, although the uterus ultimately developed suboptimally. The girls' breasts and uteruses grew quickly at the beginning of HRT (stages B2-4). An optimal HRT regimen for girls with TS may specifically focus on Tanner stages B2-4 and artificial cycles.


Assuntos
Mama/crescimento & desenvolvimento , Terapia de Reposição Hormonal , Maturidade Sexual/efeitos dos fármacos , Síndrome de Turner/tratamento farmacológico , Mama/efeitos dos fármacos , China , Feminino , Humanos , Estudos Longitudinais , Análise Multivariada , Estudos Retrospectivos
10.
Theriogenology ; 138: 9-15, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31279051

RESUMO

The aim of the study was to evaluate the effect on selenium supplementation on attainment of puberty in Saanen male goat kids. Forty Saanen male goats kids were divided into two groups: selenium supplemented (n = 20) and control (n = 20). The treatment group received sodium selenite at a ninety days interval for an experimental period of 150 days. All experimental Saanen male goat kids were fed Lucerne hay deficient in selenium. The development of the reproductive functions of the male goat kids was monitored until puberty. At the age of 5.5 months motile spermatozoa were collected from 65% of the supplemented group compared to 35% of the control. At 140 days following supplementation the treated group showed significantly higher semen volume per ejaculate and improved semen quality in the form of improved spermatozoa motility and concentration and a decreased percentage of dead spermatozoa, spermatozoa abnormalities and acrosome damage compared to the control. Supplementation with selenium significantly (P < 0.05) improved body weight, testicular measurements and decreased age at puberty. Selenium supplementation also led to higher (P < 0.05) LH and testosterone concentrations. It is concluded that selenium supplementation hastened age at attainment of puberty to 5.5 months in male Saanen kids as the control group attained puberty at 6 months. It also improved semen quality and reproductive hormones concentration of Saanen kids.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Cabras/crescimento & desenvolvimento , Selênio/administração & dosagem , Maturidade Sexual/efeitos dos fármacos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Masculino , Selênio/farmacologia , Análise do Sêmen/veterinária , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento
11.
Anim Reprod Sci ; 207: 21-35, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31266599

RESUMO

Organotypic culture of testicular fragments from 7-day-old male pigs (Polish White Large) was used. Tissues were treated with an antagonist of G-protein coupled estrogen receptor (GPER) (G-15; 10 nM), and bisphenol A (BPA), and its analogs (TBBPA, TCBPA; 10 nM) alone or in combination and analyzed using electron and light (stainings for collagen fibers, lipid droplet and autophagy markers) microscopes. In addition, mRNA and protein abundances and localization of molecules required for miRNA biogenesis and function (Drosha, Exportin 5; EXPO5, Dicer, and Argonaute 2; AGO2) were assessed together with calcium ion (Ca2+) and estradiol concentrations. Regardless of GPER blockade and/or treatment with BPA, TBBPA and TCBPA, there were no changes in Leydig cell morphology. Also, there were no changes in lipid droplet content and distribution but there were changes in lipid and autophagy protein abundance. In the interstitial tissue, there was an increase of collagen content, especially after treatment with BPA analogs and G-15 + BPA. Independent of the treatment, there was downregulation of EXPO5 and Dicer genes but the Drosha and AGO2 genes were markedly upregulated as a result of treatment with G-15 + BPA and TCBPA, respectively. There was always a lesser abundance of EXPO5 and AGO2 proteins regardless of treatment. There was markedly greater abundances of Drosha after G-15 + BPA treatment, and this also occurred for Dicer after treatment with G-15 + TCBPA. Immunolocalization of miRNA proteins indicated there was a cytoplasmic-nuclear pattern in control and treated cells. There was an increase of Ca2+ concentrations after treatment with G-15 and BPA analogs. Estradiol secretion decreased after antagonist and chemical treatments when these were administered alone, however, there was an increase in estradiol secretion after treatment with combinations of these compounds.


Assuntos
Compostos Benzidrílicos/farmacologia , Epigênese Genética/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Fenóis/farmacologia , Receptores Estrogênicos/fisiologia , Receptores Acoplados a Proteínas-G/fisiologia , Testículo/efeitos dos fármacos , Animais , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Interação Gene-Ambiente , Células Intersticiais do Testículo/metabolismo , Masculino , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Estrogênicos/genética , Receptores Acoplados a Proteínas-G/genética , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/genética , Suínos , Testículo/metabolismo
12.
Theriogenology ; 138: 47-51, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31284221

RESUMO

To test the hypothesis that postnatal sexual steroids induce an impairment of domestic male cat reproductive function, this study describes the physical, endocrine, steroidogenical and histological effects of a single, high dose of a postnatal sexual steroid in this species. Twenty male kittens were randomly assigned within the first 24 h of birth to: Testosterone enanthate 12.5 mg sc (TE; n = 8), medroxyprogesterone acetate 10 mg sc (MA; n = 6), or Placebo sc (PL; n = 6). The cats were followed until puberty when they were castrated. Kittens achieved puberty without age differences among groups (P > 0.05). Two MA cats presented abnormal testicular descent. Histological evaluation of the MA (P < 0.01), but not of TE testes revealed decreased diameter (P < 0.01) and epithelial height (P < 0.01) of the seminiferous tubules. Leydig cell nuclear area was also reduced in this group. Conversely, tubular/intertubular ratio was increased in TE animals (P < 0.01). Quantitative real-time PCR analysis of mRNA expression of testicular tissue revealed no significant differences among groups for StAR, CYP17A1 and androgen receptors. TE animals showed decreased CYP19A1 mRNA expression (P < 0.05). In the first 4 postnatal weeks, fecal testosterone (T) values were high, basal and intermediate in TE, MA and PL (P < 0.05), respectively. These differences progressively diminished and the three groups presented basal T concentrations from the 7th week on (P > 0.05). It was concluded that the postnatal progestagen initially suppressed the gonadal axis and caused an impairment of spermatogenesis and testicular descent at puberty. Androgen treatment caused downregulation of the final steroidogenic cascade.


Assuntos
Disruptores Endócrinos/farmacologia , Reprodução/efeitos dos fármacos , Esteroides/farmacologia , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testosterona/análogos & derivados , Animais , Animais Recém-Nascidos , Constituição Corporal/efeitos dos fármacos , Gatos , Anticoncepção/métodos , Anticoncepção/veterinária , Hormônios Esteroides Gonadais/farmacologia , Masculino , Reprodução/fisiologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/farmacologia
13.
BMC Genomics ; 20(1): 597, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331264

RESUMO

BACKGROUND: The impossibility of closing the life cycle of the European eel (Anguilla anguilla) in captivity troubles the future of this critically endangered species. In addition, the European eel is a highly valued and demanded resource, thus the successful closing of its life cycle would have a substantial economic and ecological impact. With the aim of obtaining the highest gamete quality, the study of the effects of environmental factors, such as temperature, on reproductive performance may prove valuable. This is especially true for the exposure to cold water, which has been reported to improve sexual development in multiple other Actinopterygii species. RESULTS: European eel males treated with cold seawater (10 °C, T10) for 2 weeks showed an increase in the proliferation and differentiation of spermatogonial cells until the differentiated spermatogonial type A cell stage, and elevated testosterone and 11-ketotestosterone plasma levels. Transcriptomes from the tissues of the brain-pituitary-gonad (BPG) axis of T10 samples revealed a differential gene expression profile compared to the other experimental groups, with clustering in a principal component analysis and in heat maps of all differentially expressed genes. Furthermore, a functional analysis of differentially expressed genes revealed enriched gene ontology terms involved in the regulation of circadian rhythm, histone modification, meiotic nuclear division, and others. CONCLUSIONS: Cold seawater treatment had a clear effect on the activity of the BPG-axis of European eel males. In particular, our cold seawater treatment induces the synchronization and increased proliferation and differentiation of specific spermatogonial cells. In the transcriptomic results, genes related to thermoception were observed. This thermoception may have caused the observed effects through epigenetic mechanisms, since all analysed tissues further revealed differentially expressed genes involved in histone modification. The presented results support our hypothesis that a low temperature seawater treatment induces an early sexual developmental stage in European eels. This hypothesis is logical given that the average temperature experienced by eels in the early stages of their oceanic reproductive migration is highly similar to that of this cold seawater treatment. Further studies are needed to test whether a cold seawater treatment can improve the response of European eels to artificial hormonal treatment, as the results suggest.


Assuntos
Anguilla/crescimento & desenvolvimento , Encéfalo/efeitos dos fármacos , Temperatura Baixa , Hipófise/efeitos dos fármacos , Água do Mar/química , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Anguilla/genética , Anguilla/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Masculino , Anotação de Sequência Molecular , Hipófise/metabolismo , Hipófise/fisiologia , Testículo/metabolismo , Testículo/fisiologia , Fatores de Tempo , Transcriptoma/efeitos dos fármacos
14.
Nutrients ; 11(7)2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31337124

RESUMO

Alterations in pubertal timing have been associated with long-term health outcomes. While a few reports have shown that dietary intake of selenium is associated with fertility and testosterone levels in men, no human studies have considered the association between selenium and pubertal development in children. We examined the cross-sectional association of childhood dietary intake of selenium with pubertal development among 274 girls and 245 boys aged 10-18 years in Mexico City. Multiple logistic and ordinal regression models were used to capture the association between energy-adjusted selenium intake (below Recommended Dietary Allowance (RDA) vs. above RDA) and stages of sexual maturity in children, adjusted for covariates. We found that boys with consumption of selenium below the RDA had lower odds of a higher stage for pubic hair growth (odds ratio (OR) = 0.51, 95% confidence interval (95% CI): 0.27-0.97) and genital development (OR = 0.53, 95% CI: 0.28-0.99) as well as a lower probability of having matured testicular volume (OR = 0.37, 95% CI: 0.15-0.88) compared with boys who had adequate daily dietary intake of selenium (above RDA). No associations were found in girls. According to our results, it is possible that inadequate consumption of selenium may be associated with later pubertal development in boys, suggesting a sex-specific pattern. Future work with a larger sample size and measures of selenium biomarkers is needed to confirm our findings and improve understanding of the role of this mineral in children's sexual development.


Assuntos
Dieta , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Selênio/administração & dosagem , Maturidade Sexual/efeitos dos fármacos , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México , Recomendações Nutricionais , Selênio/deficiência , Fatores Sexuais , Maturidade Sexual/fisiologia
15.
Environ Pollut ; 249: 1049-1059, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146311

RESUMO

Tebuconazole is a widely used fungicide that has been detected in water ecosystems, of which the concentrations may affect the endocrine function of aquatic organisms. At present study, tissue-specific bioaccumulation of tebuconazole was found in ovary of adult zebrafish, indicating a potential risk of endocrine disruption. In order to evaluate the potential endocrine disrupting effects, three life stages (2 hpf (hours post-fertilization) -60 dpf (days post-fertilization), Stage I; 60-120 dpf, Stage II; 180-208 dpf, Stage III) of zebrafish (Danio rerio) were chronically exposed to tebuconazole at the concentrations ranging from 0.05 mg/L to 1.84 mg/L. Result showed that exposed to tebuconazole could lead to a male-biased sex differentiation in juvenile zebrafish and significant decrease of the percentage of germ cells in sexually-mature zebrafish. Egg production was significantly inhibited by 57.8% and 19.2% after Stage II- and Stage III-exposures, respectively. The contents of 17ß-estradiol in gonad decreased by 63.5% when exposed to 0.20 mg/L tebuconazole at Stage II and by 49.5% after exposed to 0.18 mg/L tebuconazole at Stage III, respectively. For all stages exposure, reductions in 17ß-estradiol/testosterone ratio were observed, indicating an imbalance in steroids synthesis. Additionally, tebuconazole reduced the expression of cyp19a, which was consistent with the decrease of E2 level. In overall, the present findings indicated that, playing as an anti-estrogen-like chemical, tebuconazole inhibited the expression of Cyp19, thereby impairing steroid hormones biosynthesis, leading to a diminished fecundity of zebrafish.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Gônadas/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Aromatase/metabolismo , Embrião não Mamífero/metabolismo , Disruptores Endócrinos/metabolismo , Feminino , Fungicidas Industriais/metabolismo , Gônadas/embriologia , Diferenciação Sexual/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Triazóis/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo
16.
J Vet Sci ; 20(3): e30, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161748

RESUMO

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.


Assuntos
Flagelina/imunologia , Hormônio Liberador de Gonadotropina/imunologia , Infertilidade Masculina/induzido quimicamente , Orquiectomia/veterinária , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Vacinas Anticoncepcionais/normas , Animais , Anticorpos/sangue , Gatos , Escherichia coli/genética , Flagelina/genética , Hormônio Liberador de Gonadotropina/genética , Masculino , Orquiectomia/métodos , Proteínas Recombinantes/farmacologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Vacinas Anticoncepcionais/farmacologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
17.
Horm Res Paediatr ; 91(3): 153-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31167218

RESUMO

BACKGROUND: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17ß-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17ß-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. ANALYSIS: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. CONCLUSION: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions.


Assuntos
Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Maturidade Sexual/efeitos dos fármacos , Administração Cutânea , Administração Oral , Adolescente , Criança , Feminino , Humanos , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/metabolismo , Síndrome de Turner/fisiopatologia
18.
Gen Comp Endocrinol ; 282: 113209, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226256

RESUMO

The highly conserved brain-pituitary-gonadal (BPG) axis controls reproduction in all vertebrates, so analyzing the regulation of this signaling cascade is important for understanding reproductive competence. The protein kinase mechanistic target of rapamycin (mTOR) functions as a conserved regulator of cellular growth and metabolism in all eukaryotes, and also regulates the reproductive axis in mammals. However, whether mTOR might also regulate the BPG axis in non-mammalian vertebrates remains unexplored. We used complementary experimental approaches in an African cichlid fish, Astatotilapia burtoni, to demonstrate that mTOR is involved in regulation of the brain, pituitary, and testes when males rise in rank to social dominance. mTOR or downstream components of its signaling pathway (p-p70S6K) were detected in gonadotropin-releasing hormone (GnRH1) neurons, the pituitary, and testes. Transcript levels of mtor in the pituitary and testes also varied when reproductively-suppressed subordinate males rose in social rank to become dominant reproductively-active males, a transition similar to puberty in mammals. Intracerebroventricular injection of the mTORC1 inhibitor, rapamycin, revealed a role for mTOR in the socially-induced hypertrophy of GnRH1 neurons. Rapamycin treatment also had effects at the pituitary and testes, suggesting involvement of the mTORC1 complex at multiple levels of the reproductive axis. Thus, we show that mTOR regulation of BPG function is conserved to fishes, likely playing important roles in regulating reproduction and fertility across all male vertebrates.


Assuntos
Ciclídeos/fisiologia , Reprodução/fisiologia , Predomínio Social , Serina-Treonina Quinases TOR/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclídeos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/genética , Testículo/efeitos dos fármacos , Testículo/metabolismo
19.
PLoS Biol ; 17(5): e3000254, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31067225

RESUMO

Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.


Assuntos
Técnicas de Cultura de Células/métodos , Parasitos/crescimento & desenvolvimento , Schistosoma mansoni/crescimento & desenvolvimento , Animais , Ácido Ascórbico/farmacologia , Colesterol/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Haploidia , Humanos , Masculino , Camundongos , Óvulo/efeitos dos fármacos , Óvulo/fisiologia , Partenogênese/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Reprodução/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos
20.
Int J Toxicol ; 38(3): 209-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31113312

RESUMO

The objective of this study was to evaluate male pubertal changes associated with environmental low-level lead (Pb) exposure. The study was conducted on 180 boys aged 15 years divided into 3 equal size groups: group 1 from El-Newayrat village, group 2 from Al-Shorafaa (0.5 and 10 km, respectively, from an industrialized area), and group 3 from Talla (25 km). Blood Pb levels (BLLs) were measured and pubertal changes evaluated by measurement of testicular volume (TV), and estimation of the follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin. Blood Pb levels of children of El-Newayrat and Al-Shorafaa were significantly higher (6.38 [1.32] and 3.84 [0.79] µg/dL, respectively) than that of Talla children (1.85 [0.72]; P < 0.001), while height, weight, and TV were lower in boys in groups 1 and 2, compared to group 3. Genitalia and pubarche staging showed greatest retardation and marked bone growth delay in boys of group 1. Hormonal assays reported significant differences in boys of the industrialized areas when compared to that of Talla. Low-level Pb exposure in boys located near an industrial area was accompanied with altered male puberty indicators.


Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Adolescente , Egito , Poluentes Ambientais/sangue , Hormônios/sangue , Humanos , Chumbo/sangue , Masculino , Maturidade Sexual/efeitos dos fármacos
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