Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.797
Filtrar
1.
Life Sci ; 246: 117432, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32061867

RESUMO

Our previous studies have shown that prenatal cold stress leads to placental inflammatory response and induces anxiety-like behavior reduced in offspring rats. However, the role and mechanisms by which prenatal cold stress affects offspring remain unclear. The aim of this study was to determine the metabolic profiles from the maternal serum and helpful in understanding the role and mechanisms by which prenatal cold stress affects the offspring. In this study, liquid chromatography-mass spectrometry (LC/MS) was used to analyze serum metabolites, and PCA, PLS-DA, and OPLS-DA were performed to analyze changes in metabolites in the maternal serum after cold stress of 3 or 7 days. The results showed that 19 metabolites in the CS (cold stress 7 days)-NS (control) group and 23 metabolites in the CT (cold stress 3 days)-NT (control) group were significantly altered. These metabolites were mainly associated with unsaturated fatty acid synthesis, and arachidonic acid, linoleic acid, and glutamine and glutamate metabolism. The data indicated that prenatal cold stress not only affected the maternal neuroendocrine system, but also affected the immune system, and lipid and amino acid metabolism. These results further supported the findings of our previous studies on the effects of prenatal cold stress on the mother and offspring. A more comprehensive understanding of these data may lead to maternal intervention that can reverse the damage of prenatal stressors.


Assuntos
Resposta ao Choque Frio , Metabolômica , Efeitos Tardios da Exposição Pré-Natal/etiologia , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar
2.
Gene ; 731: 144354, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935513

RESUMO

BACKGROUND AND AIMS: Maternal obesity predispose offspring to metabolic disorders and obesity, but the mechanisms are not fully understood, especially during early life. Circular RNA (circRNA) can regulate the expression of target genes through the regulatory pathways of competing endogenous RNA (ceRNA). We hypothesized that the offspring of obese dams exhibit impaired metabolic health through the dysregulated expression of hepatic circRNA. METHODS AND RESULTS: A high-fat diet (HFD) or standard chow diet (CD) were randomized to dams for 12 weeks before mating. Specific diets continued for each dam throughout pregnancy and lactation. Then, lipid metabolic parameters were assessed in dams and female offspring. We performed liver RNA sequencing (RNA-seq) for the offspring of HFD- and CD-dams to comprehensively identify differentially expressed (DE) circRNA and messenger RNA (mRNA). Further, ceRNA networks combining DE circRNA, mRNA, and microRNA were predicted based on MiRanda and TargetScan databases combined with the lipid metabolism-related pathway. As a result, the circRNA_0000660-miR_693-Igfbp1 regulatory pathway was selected from liver and AML12 cell line. Quantitative real-time polymerase chain reaction, dual luciferase reporter gene system, and Small interfering RNA for circRNA_0000660 transfection experiment were applied to validate. CONCLUSIONS: Our work investigated new mechanisms of the effect of maternal obesity on offspring's lipid metabolism. Several novel targets were uncovered to reverse the effect.


Assuntos
Fígado/metabolismo , MicroRNAs/genética , Efeitos Tardios da Exposição Pré-Natal/genética , /genética , Animais , Animais Lactentes , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , /metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Desmame
3.
Food Chem Toxicol ; 135: 110897, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654709

RESUMO

The mechanisms of prenatal cadmium (Cd) exposure cause adverse effect transmission to future generations that remain unclear. In this study, pregnant SD rats were orally dosed with Cd (0, 0.5, 2.0, and 8.0 mg/kg/day) from gestation day 1 until birth. F1 female rats were mated with untreated males for F2 generation. In both generations, after prenatal Cd exposure, histopathological examinations showed testicular development disorder. A significant decrease in serum testosterone (T) was observed in the F1 rats, but a significant increase in serum T was observed in the F2 rats. Moreover, both the F1 and F2 rats had different patterns of mRNA and protein expression for testicular steroidogenic factor 1 (SF-1) and steroidogenic enzymes at postnatal days (PNDs) 21 and 56. We also found that rno-miR-328a-5 and rno-miR-10b-5p significantly changed and TargetScan software showed that both of these microRNAs targeted SF-1 and steroidogenic acute regulatory (StAR), respectively. Overall, the results indicate that prenatal Cd exposure causes male reproductive problems in a multigenerational manner. In addition, SF-1 signaling was disrupted and the expressions of microRNAs were affected, which may be an important target for Cd-induced reproductive toxicity in offspring.


Assuntos
Cádmio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Exposição Materna/efeitos adversos , MicroRNAs/metabolismo , Gravidez , Progesterona/metabolismo , Ratos Sprague-Dawley , Testículo/patologia
4.
J Sci Food Agric ; 100(4): 1486-1494, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756772

RESUMO

BACKGROUND: We reported previously that maternal betaine promotes hepatic insulin-like growth factor (IGF2) expression in F1 offspring rats through hypermethylation of the IGF2/H19 imprinting control region (ICR). It remains unknown whether this acquired trait can be transmitted to the F2 generation. This study aimed to determine whether dietary betaine supplementation to grand dams affects the hepatic IGF2 expression in F2 rat offspring and how it is related to alterations in DNA methylation. F2 rat offspring derived from grand dams fed basal or betaine-supplemented diet (10 g kg-1 ) were examined at weaning. Serum IGF2 concentration was measured with enzyme-linked immunosorbent assay (ELISA). Hepatic expression of IGF2, together with other proliferation and apoptosis markers, was determined by using quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry. The methylation status of the IGF2/H19 ICR and the promoters of IGF2 gene were detected by methylated DNA immunoprecipitation quantitative polymerase chain reaction (MeDIP-qPCR). RESULTS: The maternal betaine-induced up-regulation of hepatic IGF2 expression in F1 rat offspring was transmitted to the F2 generation. The F2 rats from the betaine group demonstrated enhanced hepatic IGF2 expression at both mRNA and protein levels, in association with higher serum IGF2 concentration. No alterations were observed in the ICR methylation of the IGF2/H19 locus, and hypomethylation was detected in promoters of IGF2 gene in betaine group. CONCLUSION: These results indicate that maternal betaine enhances hepatic IGF2 expression in F2 rat offspring through modification of DNA methylation on IGF2 promoters. © 2019 Society of Chemical Industry.


Assuntos
Betaína/administração & dosagem , Metilação de DNA/efeitos dos fármacos , Fator de Crescimento Insulin-Like II/genética , Fígado/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Animais , Suplementos Nutricionais/análise , Feminino , Fator de Crescimento Insulin-Like II/metabolismo , Fígado/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Linhagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley
5.
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
6.
Endocrinology ; 161(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875912

RESUMO

Changes in gonadotropin-releasing hormone (GnRH) release frequency from the brain help drive reproductive cycles. In polycystic ovary syndrome (PCOS), persistent high GnRH/luteinizing hormone (LH) frequency disrupts cycles and exacerbates hyperandrogenemia. Adult prenatally-androgenized (PNA) mice exhibit increased GnRH neuron firing rate, elevated ovarian androgens, and disrupted cycles, but before puberty, GnRH neuron activity is reduced in PNA mice compared with controls. We hypothesized that ovarian feedback mediates the age-dependent change in GnRH neuron firing rate in PNA vs control mice. Extracellular recordings of green fluorescent protein (GFP)-identified GnRH neurons were made 5 to 7 days after sham-surgery, ovariectomy (OVX), or, in adults, after OVX plus replacement of sub-male androgen levels with dihydrotestosterone implants (OVX + DHT). In 3-week-old mice, OVX did not affect GnRH neuron firing rate in either group. In adult controls, OVX increased GnRH neuron firing rate, which was further enhanced by DHT. In adult PNA mice, however, OVX decreased GnRH neuron firing rate, and DHT restored firing rate to sham-operated levels. In contrast to the differential effects of ovarian feedback on GnRH neuron firing rate, serum LH increased after OVX in both control and PNA mice and was not altered by DHT. Pituitary gene expression largely reflected changes expected with OVX, although in PNA but not control mice, DHT treatment increased Lhb expression. These results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback. PNA lowers GnRH neuron activity in low-steroid states (before puberty, OVX), and renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens.


Assuntos
Androgênios/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/fisiologia , Ovário/metabolismo , Animais , Di-Hidrotestosterona/farmacologia , Eletrofisiologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ovariectomia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Maturidade Sexual/fisiologia
7.
Environ Toxicol ; 35(1): 15-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31454150

RESUMO

The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Finasterida/toxicidade , Genitália Feminina/efeitos dos fármacos , Gerbillinae/embriologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Próstata/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Genitália Feminina/embriologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Próstata/embriologia , Receptores Androgênicos/metabolismo , Reprodução/efeitos dos fármacos , Testosterona/metabolismo
8.
Ecotoxicol Environ Saf ; 188: 109918, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31753310

RESUMO

Hormonal regulation controls mammary gland (MG) development. Therefore some hormone-related factors can disrupt the early phases of MGs development, making the gland more susceptible to long term modifications in its response to circulating hormones. Endocrine disruptors, such as bisphenol A (BPA), are able to cause alterations in hormone receptor expression, leading to changes in the cell proliferation index, which may expose the tissue to neoplastic alterations. Thus, we evaluated the variations in hormone receptor expression in the MG of 6-month old Mongolian gerbils exposed to BPA and 17ß estradiol during the perinatal period. Receptors for estrogen alpha (ERα), beta (ERß), progesterone (PGR), prolactin (PRL-R), and co-localization of connexin 43 (Cx43) and ERα in gerbils were analyzed, and serum concentrations of estradiol and progesterone were assessed. No alterations in body, liver, and ovary-uterus complex weights were observed. However, there was an increase in epithelial ERα expression in the 17ß estradiol (E2) group and in PGR in the BPA group. Although immunohistochemistry did not show alterations in ERß expression, western blotting revealed a decrease in this protein in the BPA group. PRL-R was more present in epithelial cells in the vehicle control (VC), E2, and BPA groups in comparison to the intact control group. Cx43 was more frequent in E2 and BPA groups, suggesting a protective response from the gland against possible malignancy. Serum concentration of estradiol reduced in VC, E2, and BPA groups, confirming that alterations also impacts steroid levels. Consequently, perinatal exposure to BPA and the reference endogenous estrogen, 17ß estradiol, are able to increase the tendency of endocrine disruption in MG in a long term manner, since repercussions are observed even 6 months after exposure.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Gerbillinae , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
9.
Environ Pollut ; 255(Pt 1): 113366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668954

RESUMO

Air pollution is one of the leading preventable threats to public health. Emerging evidence indicates that exposure to environmental stressors is associated with abnormal foetal development. However, how prenatal exposure to diesel exhaust PM2.5 (DEP) predisposes adult offspring to the development of non-alcoholic fatty liver disease (NAFLD) remains unclear. To examine this, C57BL/6J mice were exposed to DEP or a vehicle before conception and during pregnancy and fed normal chow or a high-fat diet. Then, the hepatic fatty accumulation in the adult male offspring and possible molecular mechanisms were assessed. Our data showed that prenatal exposure to DEP on normal chow led to hepatic steatosis in adult male offspring with normal liver function. However, prenatal DEP exposure relieved the hepatic steatosis and liver function in offspring of mice fed a high-fat diet. Furthermore, prenatal exposure to DEP on normal chow increased lipogenesis and worsened fatty acid oxidation. The counteractive effect of prenatal DEP exposure on high-fat-diet-induced hepatic steatosis was produced through upregulated adenosine 5'-monophosphate-activated protein kinase, and this improved lipogenesis and fatty acid oxidation. Collectively, prenatal exposure to DEP programmed the development of NAFLD differently in the adult male offspring of mice fed normal chow and a high-fat diet, showing the pleotrophic effects of exposure to adverse environmental factors in early life.


Assuntos
Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Crianças Adultas , Poluição do Ar , Animais , Feminino , Desenvolvimento Fetal , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo
10.
J Agric Food Chem ; 67(48): 13269-13281, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31725275

RESUMO

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Pâncreas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Animais , Diabetes Gestacional/metabolismo , Gorduras/metabolismo , Feminino , Humanos , Masculino , Metabolômica , Pâncreas/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Telômero/metabolismo
11.
Life Sci ; 239: 117038, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730868

RESUMO

AIM: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia. MAIN METHODS: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively. KEY FINDINGS: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both). SIGNIFICANCE: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Pré-Eclâmpsia/dietoterapia , Vitamina E/uso terapêutico , Animais , Apoptose/fisiologia , Biomarcadores/metabolismo , Caspase 3/análise , Caspase 3/sangue , Caspase 8/análise , Caspase 8/sangue , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/metabolismo , Feminino , Masculino , Fenômenos Fisiológicos da Nutrição/fisiologia , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Vitamina E/metabolismo , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/sangue
12.
Nat Neurosci ; 22(12): 1975-1985, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31611707

RESUMO

The increased legal availability of cannabis has led to a common misconception that it is a safe natural remedy for, among others, pregnancy-related ailments such as morning sickness. Emerging clinical evidence, however, indicates that prenatal cannabis exposure (PCE) predisposes offspring to various neuropsychiatric disorders linked to aberrant dopaminergic function. Yet, our knowledge of how cannabis exposure affects the maturation of this neuromodulatory system remains limited. Here, we show that male, but not female, offspring of Δ9-tetrahydrocannabinol (THC)-exposed dams, a rat PCE model, exhibit extensive molecular and synaptic changes in dopaminergic neurons of the ventral tegmental area, including altered excitatory-to-inhibitory balance and switched polarity of long-term synaptic plasticity. The resulting hyperdopaminergic state leads to increased behavioral sensitivity to acute THC exposure during pre-adolescence. The neurosteroid pregnenolone, a US Food and Drug Administration (FDA) approved drug, rescues synaptic defects and normalizes dopaminergic activity and behavior in PCE offspring, thus suggesting a therapeutic approach for offspring exposed to cannabis during pregnancy.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Dronabinol/efeitos adversos , Dronabinol/farmacologia , Pregnenolona/farmacologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Dronabinol/antagonistas & inibidores , Endofenótipos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Atividade Motora/efeitos dos fármacos , Inibição Neural/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Gravidez , Inibição Pré-Pulso/efeitos dos fármacos , Inibição Pré-Pulso/fisiologia , Ratos , Assunção de Riscos , Filtro Sensorial/efeitos dos fármacos , Filtro Sensorial/fisiologia , Caracteres Sexuais , Área Tegmentar Ventral/metabolismo
13.
Food Funct ; 10(11): 7216-7226, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31612177

RESUMO

Offspring of dams exposed to excess folic acid during the perigestational period have been shown by us to be predisposed to metabolic dysfunction revealed by hyperglycemia, glucose intolerance, increased insulin and decreased adiponectin in late adulthood. This work aims to characterize adipocyte phenotype and expression profile of genes in the regulation of lipid and glucose metabolism in visceral adipose tissue and in skeletal muscle. From mating until weaning, a recommended dose of folic acid for pregnancy (C, 2 mg of folic acid per kg of diet) or a high folic acid dose (HFA, 40 mg of folic acid per kg of diet) was administered to Sprague-Dawley females. At 10 months of age progeny were divided into groups fed the standard chow (C/STD and HFA/STD) and groups fed the standard chow plus drinking water with 10% fructose (C/FRU and HFA/FRU), as an additional metabolic challenge. Adipocyte morphology and quantification of key genes involved in lipid and glucose metabolism were studied in visceral adipose tissue and skeletal muscle of 13 months old offspring. HFA exposure led to an enlargement of visceral adipose cells most likely mediated by an upregulation of lipoprotein lipase, and it tended to downregulate Glut4 in visceral adipose tissue and skeletal muscle. Fructose exposure in a background of perigestational excess folic acid, but not in controls, induced an upregulation of lipogenesis pathway genes and it decreased jejunal expression of the proton-coupled folate transporter (Pcft1). In addition, fructose exposure led to a downregulation of jejunal Sglt1 in control animals. Our data suggest that high folic acid exposure during the perigestational period caused morphologic and genic alterations related to insulin resistant states indicating that this intervention may act as an effective programmer of long-term metabolic dysfunction.


Assuntos
Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Doenças Metabólicas/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Animais , Suplementos Nutricionais/análise , Feminino , Ácido Fólico/administração & dosagem , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Músculo Esquelético/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transportador de Folato Acoplado a Próton/genética , Transportador de Folato Acoplado a Próton/metabolismo , Ratos , Ratos Sprague-Dawley
14.
J Physiol Pharmacol ; 70(3)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31539886

RESUMO

A balanced maternal diet is necessary for the proper health and development of offspring. Recent clinical and preclinical studies have strongly indicated that maternal exposure to a high-fat diet (HFD) can have an irreversible impact on the structure and function of the offspring's brain and affect the immune system, which may predispose the offspring to brain disorders, including depression. The irisin/brain-derived neurotrophic factor (BDNF) axis is a pathway that influences several neurobehavioral mechanisms involved in the pathogenesis of mental disorders. The aim of the present study was to evaluate the influence of a maternal HFD during pregnancy and lactation on depressive-like behavior, serum irisin concentration and hippocampal levels of irisin, BDNF and inflammatory factors (interleukin-1α, interleukin-6 and tumor necrosis factor-α) in adolescent and adult male and female offspring. The main findings indicate that offspring exposed to a maternal HFD are characterized by an increased immobility time in the forced swimming test at both stages of life. Our results showed that a maternal HFD decreased serum and hippocampal irisin levels in females on postnatal day (PND) 28 and decreased the level of interleukin-1α at postnatal days 28 and 63 in the hippocampus. Interestingly, significant age-dependent changes were observed in irisin, BDNF and interleukin levels. To summarize, our study indicates that a maternal HFD during pregnancy and lactation provokes depressive-like behaviour in the offspring. However, despite the observed changes in the levels of irisin and IL-1α in females, further investigations are required to identify the underlying molecular mechanism associated with depressive-like behavior in the offspring of HFD-fed dams.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lactação/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Comportamento Animal , Feminino , Hipocampo/metabolismo , Masculino , Gravidez , Ratos
15.
Acta Histochem ; 121(7): 841-851, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31431301

RESUMO

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disease characterized by defect in verbal and nonverbal communications. As, the cerebellum has the greatest number of neurons and synapses in the central nervous system so, the cerebellum has emerged as one of the target brain areas affected in autism. The aim of this work was to study the biochemical, immunohistochemical and ultrastructural characteristics of autism and the possible neuroprotective role of grape seed extract. In this study 28 male pups were divided into Control groups; Group I (saline), Group II (GSE 400 mg/kg), Group III (VPA 500 mg/kg) and Group IV (VPA and GSE). Cerebellar hemispheres were dissected out and prepared to determine the oxidative stress markers, histological, immunohistochemical and morphometric study were done. A significant elevation in oxidative stress markers in off spring of VPA treated rats in comparison to control group was detected. A significant decrease in the Purkinje cell count and nuclear size were observed. Numerous shrunken cells with hyperchromatic nuclei and ultrastructural degeneration of cytoplasmic organelles were detected. A significant rise in the area percentage of GFAP-positive immune stained cells in comparison to that of the control groups was seen. Strikingly, GSE revealed significant improvement in the oxidative stress markers and then the histological and morphometric picture of the cerebellum. GSE has neuroprotective effect on the cerebellum of VPA treated rats through its potent antioxidant effect.


Assuntos
Transtorno Autístico , Córtex Cerebelar , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Sementes/química , Ácido Valproico/efeitos adversos , Vitis/química , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Transtorno Autístico/prevenção & controle , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Modelos Animais de Doenças , Feminino , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos , Ácido Valproico/farmacologia
16.
PLoS Biol ; 17(8): e3000086, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31433818

RESUMO

Lengthy use of general anesthetics (GAs) causes neurobehavioral deficits in the developing brain, which has raised significant clinical concerns such that the United States Food and Drug Administration (FDA) is warning on the use of GAs in children younger than 3 years. However, the molecular and cellular mechanisms for GAs-induced neurotoxicity remain largely unknown. Here, we report that sevoflurane (Sevo), a commonly used GA in pediatrics, caused compromised astrocyte morphogenesis spatiotemporally correlated to synaptic overgrowth, with reduced synaptic function in developing cortex in a regional-, exposure-length-, and age-specific manner. Sevo disrupted astrocyte Ca2+ homeostasis both acutely and chronically, which led to the down-regulation of Ezrin, an actin-binding membrane-bound protein, which we found was critically involved in astrocyte morphogenesis in vivo. Importantly, overexpression of astrocyte Ezrin rescued astrocytic and neuronal dysfunctions and fully corrected deficits in social behaviors in developing mice with lengthy Sevo exposure. Our data uncover that, in addition to neurons, astrocytes may represent important targets for GAs to exert toxic effects and that astrocyte morphological integrity is crucial for synaptogenesis and neurological behaviors.


Assuntos
Astrócitos/efeitos dos fármacos , Sevoflurano/efeitos adversos , Sinapses/efeitos dos fármacos , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Proteínas do Citoesqueleto/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Comportamento Social
17.
Niger J Physiol Sci ; 34(1): 11-16, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449266

RESUMO

Monosodium glutamate (MSG) is a widely-consumed taste enhancer which has been implicated in the aetiology of renal and hepatic dysfunction in adults and their offspring. There is increasing evidence on the therapeutic properties of Coconut Water (CW) in kidney and liver disorders. This study investigated the effects of CW on renal and hepatic functions in offspring of MSG-fed dams. Twelve female Wistar rats (120 - 140 g) were grouped into four as follows; Control (10 ml/Kg distilled water), MSG (0.08 mg/Kg), CW (10 ml/Kg) and MSG+CW. Treatments were given orally daily commencing two weeks prior to mating, throughout mating and gestation until parturition. All dams received standard rodent diet and drinking water ad libitum throughout the study. After weaning on Post-Natal Day (PND) 28, serum was obtained from offspring for assay of liver and renal function. Histological analysis of the livers and kidneys were performed on both dams and offspring. There was no significant difference in liver enzymes, urea, creatinine and albumin levels amongst the offspring on PND 28. However, liver and kidney sections from MSG dams and their offspring showed early degenerative changes which were not evident in renal and hepatic tissues from CW and MSG+CW dams and offspring. These observations suggest that coconut water protects against monosodium glutamate-induced renal and hepatic dysfunction in dams and offspring.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cocos , Aromatizantes/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Glutamato de Sódio/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Feminino , Aromatizantes/administração & dosagem , Nefropatias/metabolismo , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Glutamato de Sódio/administração & dosagem
18.
Genesis ; 57(7-8): e23326, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31299141

RESUMO

While common in the general population, the developmental origins of "normal" anatomic variants of the aortic arch remain unknown. Aortic arch development begins with the establishment of the second heart field (SHF) that contributes to the pharyngeal arch arteries (PAAs). The PAAs remodel during subsequent development to form the mature aortic arch and arch vessels. Retinoic acid signaling involving the biologically active metabolite of vitamin A, plays a key role in multiple steps of this process. Recent work from our laboratory indicates that the E3 ubiquitin ligase Hectd1 is required for full activation of retinoic acid signaling during cardiac development. Furthermore, our study suggested that mild alterations in retinoic acid signaling combined with reduced gene dosage of Hectd1, results in a benign aortic arch variant where the transverse aortic arch is shortened between the brachiocephalic and left common carotid arteries. These abnormalities are preceded by hypoplasia of the fourth PAA. To further explore this interaction, we investigate whether reduced maternal dietary vitamin A intake can similarly influence aortic arch development. Our findings indicate that the incidence of hypoplastic fourth PAAs, as well as the incidence of shortened transverse arch are increased with reduced maternal vitamin A intake during pregnancy. These studies provide new insights as to the developmental origins of these benign aortic arch variants.


Assuntos
Aorta Torácica/embriologia , Síndromes do Arco Aórtico/etiologia , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Deficiência de Vitamina A/metabolismo , Vitamina A/metabolismo , Animais , Aorta Torácica/anormalidades , Aorta Torácica/anatomia & histologia , Feminino , Camundongos , Gravidez , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
19.
Part Fibre Toxicol ; 16(1): 27, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266526

RESUMO

BACKGROUND: Obesity is an uncontrolled global epidemic and one of the leading global public health challenges. Maternal exposure to ambient fine particulate matter (PM2.5) may adversely program offspring's adiposity, suggesting a specialized role of PM2.5 pollution in the global obesity epidemic. However, the vulnerable window for this adverse programming and how it is cross-generationally transmitted have not been determined. Therefore, in the present study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during different periods, and the development and adulthood adiposity of their four-generational offspring were assessed. RESULTS: Our data show that the pre-conceptional but not gestational exposure to CAP was sufficient to cause male but not female offspring's low birth weight, accelerated postnatal weight gain, and increased adulthood adiposity. These adverse developmental traits were transmitted into the F2 offspring born by the female but not male F1 offspring of CAP-exposed dams. In contrast, no adverse development was noted in the F3 offspring. CONCLUSIONS: The present study identified a pre-conceptional window for the adverse programming of adiposity by maternal exposure to PM2.5, and showed that it was maternally transmitted into the third generation. These data not only call special attention to the protection of women from exposure to PM2.5, but also may facilitate the development of intervention to prevent this adverse programming.


Assuntos
Adiposidade/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Exposição Materna/efeitos adversos , Obesidade/induzido quimicamente , Material Particulado/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adiposidade/genética , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Predisposição Genética para Doença , Recém-Nascido de Baixo Peso , Masculino , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Tamanho da Partícula , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores Sexuais , Ganho de Peso
20.
Hypertension ; 74(3): 518-525, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327271

RESUMO

Although maternal high-fructose intake induces cardiometabolic syndrome in adult offspring, whether it induces hypertension in successive multiple generations has not yet been studied. We hypothesized that maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Pregnant mice were offered 20% fructose in drinking water, of which subsequent first to fourth generation offspring were raised without being offered fructose. Blood pressure was measured via the tail-cuff method, mRNA expression was determined using the quantitative polymerase chain reaction, and fibrosis was evaluated using trichrome staining. Maternal high-fructose intake statistically significantly increased blood pressure in the first and second, but not the third and fourth, generation offspring as compared to the control group, with maximal increases in serum renin, angiotensin II, and aldosterone in the third generation offspring. It increased the mRNA expression of renin-angiotensin-aldosterone system genes as well as the expression of renin in the kidneys in the first to third generation offspring, with the exception of the vasodilatory Mas1 gene, the mRNA expression of which was the lowest in the second generation offspring. Moreover, it maximally increased fibrosis and the mRNA expression of inflammatory cytokines in the second generation offspring and increased the mRNA expression of oxidative factors in the first to third generation offspring, but maximally decreased the mRNA expression of antioxidant-encoding Sod1 in the second generation offspring. Maternal high-fructose intake induces multigenerational activation of renin-angiotensin-aldosterone system, and the results of this study implicate that it epigenetically induces cardiometabolic syndrome in multiple generations of offspring.


Assuntos
Frutose/efeitos adversos , Hipertensão/etiologia , Prenhez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , RNA Mensageiro/genética , Sistema Renina-Angiotensina/genética , Animais , Animais Recém-Nascidos , Biópsia por Agulha , Modelos Animais de Doenças , Características da Família , Feminino , Frutose/administração & dosagem , Predisposição Genética para Doença/genética , Hipertensão/fisiopatologia , Imuno-Histoquímica , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Distribuição Aleatória , Valores de Referência , Medição de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA