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1.
Adv Exp Med Biol ; 1191: 523-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002944

RESUMO

Exposure therapy, a key treatment for anxiety disorders, can be modelled in the laboratory using Pavlovian fear extinction. Understanding the hormonal and neurobiological mechanisms underlying fear extinction in females, who are twice more likely than males to present with anxiety disorders, may aid in optimising exposure therapy outcomes in this population. This chapter will begin by discussing the role of the sex hormones, estradiol and progesterone, in fear extinction in females. We will also propose potential mechanisms by which these hormones may modulate fear extinction. The second half of this chapter will discuss the long-term hormonal, neurological and behavioural changes that arise from pregnancy and motherhood and how these changes may alter the features of fear extinction in females. Finally, we will discuss implications of this research for the treatment of anxiety disorders in women with and without prior reproductive experience.


Assuntos
Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/terapia , Ansiedade/metabolismo , Ansiedade/terapia , Estradiol/metabolismo , Progesterona/metabolismo , Reprodução , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Extinção Psicológica , Medo , Feminino , Humanos , Gravidez
2.
Sci Total Environ ; 701: 134930, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726410

RESUMO

Natural and synthetic progestogens in livestock environments have become a concern due to the frequent presence and potential adverse effects on aquatic organisms. Here we investigated the biotransformation of progestogens by wastewater-borne bacteria in the field and laboratory under oxic and anoxic conditions. The results showed that all progestogens dissipated faster under oxic conditions than under anoxic conditions, and natural progesterone transformed faster than synthetic progestogens. Meanwhile, dozens of bacterial strains capable of degrading progestogens were successfully isolated from the swine wastewater, and Bacillus sp. P19 and Bacillus sp. DGT2 were found the best for progesterone and dydrogesterone transformation, respectively. In the degradation experiments using a single bacterial strain, progesterone and dydrogesterone dissipated under oxic conditions with half-lives of 11.6 h and 18.2 h, respectively. The transformation pathways were proposed based on the identified transformation products. The findings from this study showed that progestogens can be biotransformed, but not fully mineralized in the environment.


Assuntos
Didrogesterona/metabolismo , Progesterona/metabolismo , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Cinética , Eliminação de Resíduos Líquidos , Águas Residuárias/química
3.
J Sci Food Agric ; 100(1): 92-101, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435952

RESUMO

BACKGROUND: Oyster polypeptides have various biofunctions, such as anti-cancer and anti-oxidative stress, but whether it has the protective effects to primary ovarian failure (POF) remains poorly understand. To address this issue, daily gavage of oyster polypeptides was performed to investigate their protective effect, basing on d-galactose-induced POF model in C57BL/6 female mice. RESULTS: Oyster polypeptides restored the irregular estrous cycles and the abnormal serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P) levels as well as the decreased mRNA expression level of Amh that were induced by d-galactose. The follicle development of POF mice was improved by increasing the primordial follicle ratio and decreasing the atretic follicle number after oral administration of oyster polypeptides. Moreover, in the oyster polypeptides treated mice, the total superoxide dismutase (T-SOD) activity was significantly increased, while the malondialdehyde levels were significantly decreased. The mRNA expression levels of stress-related genes (SOD2, SIRT1 and FOXO3a) were remarkably up-regulated after d-galactose induction, but the up-regulation was weakened or disappeared by the gavage of oyster polypeptides. In addition, oyster polypeptides treatment also reduced the apoptosis of the ovarian granulosa cells and down-regulated the mRNA expression levels of apoptosis-related genes (p53 and Bad but not Bcl-2). CONCLUSION: This study reveals that oyster polypeptides may protect ovary against d-galactose-induced POF by their anti-oxidative stress activity to rescue d-galactose-induced ovarian oxidative damage and therefore to prevent ovarian cells apoptosis, thereby tipping the abnormality trigged by POF to get close to the normal levels. © 2019 Society of Chemical Industry.


Assuntos
Ostreidae/química , Peptídeos/administração & dosagem , Insuficiência Ovariana Primária/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Feminino , Galactose/efeitos adversos , Humanos , Hormônio Luteinizante/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/metabolismo , Progesterona/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
4.
Eat Behav ; 35: 101337, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726420

RESUMO

OBJECTIVE: Eating disorder symptoms change in a predictable pattern over the menstrual cycle such that changes in symptoms are triggered by changes in the ovarian hormones estradiol (E2) and progesterone (P4). To date, work in this area has focused exclusively on young adult women. The objective of this pilot study was to examine the effect of E2 and P4 on eating disorder symptom change in midlife women during early perimenopause. METHOD: Participants included women aged 42-52 in early perimenopause (n=8). In-home self-assessments were completed for one menstrual cycle or 40-days, whichever occurred first. In-home self-assessments included collecting saliva samples each morning for E2 and P4 assays and completing online study questionnaires at the end of each day. Multilevel regression models examined the associations of E2 and P4 with daily symptoms of binge eating and body dissatisfaction. RESULTS: E2 was positively associated with binge eating when P4 was high, but not when P4 was low. E2 was inversely associated with body dissatisfaction when P4 was low, but positively associated with body dissatisfaction when P4 was high. However, the simple slopes for the effect of E2 at both high and low P4 were not significant for body dissatisfaction. CONCLUSIONS: Despite the pilot nature of this study, results are broadly consistent with the young adult literature indicating that P4 levels shape the impact of E2 on eating disorder symptoms. Larger studies with the inclusion of key moderators to account for individual heterogeneity are needed to confirm and extend these findings.


Assuntos
Bulimia/metabolismo , Estradiol/metabolismo , Menopausa/fisiologia , Ovário/metabolismo , Progesterona/metabolismo , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto
5.
J Dairy Sci ; 102(11): 10514-10529, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521363

RESUMO

The objectives of this study were to investigate the carryover effects of differing pre- and postweaning planes of nutrition on prepubertal reproductive tract development and postpubertal estrous cycle characteristics in Holstein heifers. Heifer calves (n = 36) were randomly assigned to receive either a low or a high (5 or 10 L of whole milk/d, respectively) preweaning diet from 1 to 7 wk of age and either a low or a high (70 or 85% of concentrate dry total mixed ration, respectively) postweaning diet from 11 to 25 wk of age. Starting at wk 26 of age, heifers were subjected to weekly transrectal ultrasonography until wk 33 or until first ovulation to assess endometrial thickness and ovarian follicular count and size in the prepubertal phase. In a subset of heifers (n = 28), ovarian ultrasonography continued weekly until at least the second ovulation was confirmed; thereafter, ovarian dynamics (through ultrasonography) and blood progesterone (P4) were assessed every 2 d throughout 1 complete estrous cycle in the postpubertal phase. In the prepubertal phase, endometrial thickness (12.0 ± 0.4 vs. 10.8 ± 0.3 mm) and largest follicle size (11.8 ± 0.3 vs. 10.9 ± 0.2 mm) were greater in heifers fed the high postweaning diet than in those fed the low postweaning diet. Furthermore, the number of class 2 (6-9 mm) follicles was greater in heifers fed the high preweaning diet than in those fed the low preweaning diet (1.6 ± 0.1 vs. 1.1 ± 0.1), whereas the number of class 3 (>9 mm) follicles was greater in heifers fed the high postweaning diet than in those fed the low postweaning diet (1.2 ± 0.1 vs. 1.0 ± 0.1). In the postpubertal phase, overall corpus luteum and P4 dynamics did not differ among pre- or postweaning treatments; however, P4 at 4 d preceding luteolysis was lesser in heifers fed the high postweaning diet than in those fed the low postweaning diet (6.1 ± 0.4 vs. 7.7 ± 0.4 ng/mL). In addition, compared with heifers fed the low postweaning diet, those fed the high postweaning diet had a greater number of antral follicles (31.4 ± 2.2 vs. 21.4 ± 2.3) and tended to have more class 3 follicles (3.6 ± 0.3 vs. 2.7 ± 0.3). Results indicate positive carryover effects of increasing the preweaning plane of nutrition from 5 to 10 L of whole milk/d on prepubertal follicular growth in Holstein heifers. Furthermore, an increased postweaning plane of nutrition (85 vs. 70% of concentrate dry total mixed ration) advanced reproductive development through greater endometrial thickness and follicular growth in the prepubertal phase and increased the population of antral follicles in the postpubertal estrous cycle.


Assuntos
Bovinos/fisiologia , Dieta/veterinária , Ciclo Estral/fisiologia , Leite/fisiologia , Ovário/crescimento & desenvolvimento , Animais , Bovinos/crescimento & desenvolvimento , Corpo Lúteo/crescimento & desenvolvimento , Feminino , Estado Nutricional , Folículo Ovariano/crescimento & desenvolvimento , Ovário/diagnóstico por imagem , Progesterona/metabolismo , Distribuição Aleatória , Ultrassonografia/veterinária , Desmame , Ganho de Peso
6.
Anim Reprod Sci ; 208: 106110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405469

RESUMO

Adiponectin is an adipocyte derived cytokine implicated in energy homeostasis, insulin resistance and is involved in the regulation of reproduction both centrally and peripherally in animals. The present study was conducted to investigate adiponectin (ADIPOQ) and its receptors ADIPOR1 and ADIPOR2 abundance of mRNA transcript and protein in different stages of corpora lutea (CL) development during the estrous cycle of water buffalo and to determine the effect of adiponectin on cultured luteal cells of water buffalo (Bubalus bubalis). The results indicate adiponectin, ADIPOR1, and ADIPOR2 were present in buffalo corpora lutea (CL) throughout the estrous cycle. The abundance of adiponectin and its receptors was greater in the early and regressing and was less in mid- and late-stages of CL functionality. Adiponectin and its receptors were localized in the cytoplasm of small and large luteal cells. Furthermore, luteal cells were cultured in the in-vitro culture system and were treated with 1 and 10 µg/mL dose of adiponectin for 48 h. Adiponectin at both doses decreased (P < 0.05) progesterone (P4) secretion from cultured luteal cells and also suppressed the abundance of factors involved in P4productionv [Steroidogenic Acute Regulatory Protein (STAR), cytochrome P45011A1 (CYP11A1) and 3ß-hydroxysteroid dehydrogenase (HSD3B1) at the 10 µg/mL dose as compared to adiponectin non-supplemented cells]. In conclusion, results of the present study indicate adiponectin and its receptors are present in bubaline CL and adiponectin inhibits P4 production in cultured luteal cells. The findings indicate adiponectin affects luteal dynamics and reproductive functions in water buffalo.


Assuntos
Adiponectina/metabolismo , Búfalos/fisiologia , Corpo Lúteo/metabolismo , Ciclo Estral/fisiologia , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/metabolismo , Adiponectina/genética , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Feminino , Imuno-Histoquímica , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Progesterona/metabolismo , Progesterona Redutase/genética , Progesterona Redutase/metabolismo , RNA Mensageiro/genética , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Esteroide Isomerases/genética , Esteroide Isomerases/metabolismo
7.
J Steroid Biochem Mol Biol ; 194: 105460, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31470110

RESUMO

The bile acid receptor Farnesoid-X-Receptor alpha (FXRα), a member of the nuclear receptor superfamily, is well known for its roles in the enterohepatic tract. In addition, FXRα regulates testicular physiology through the control of both endocrine and exocrine functions. The endocrine function of the Leydig cells is mainly controlled by the hypothalamo-pituitary axis viaLH/chorionic gonadotropin (CG). If FXRα was demonstrated to control the expression of the Lhcgr gene, encoding the LH receptor; the impact of the LH/CG signaling on the Fxrα expression has not been defined so far. Here, we demonstrate that hCG increases the Fxrα gene expression through the protein kinase-A signaling pathway. Fxrα is then involved in a negative feedback of steroid synthesis. These data improve our knowledge of the local control of the testicular steroidogenesis with the identification of the link between the hypothalamo-pituitary axis and the FXRα signaling pathway.


Assuntos
Gonadotropina Coriônica/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Testículo/efeitos dos fármacos , Animais , Linhagem Celular , Masculino , Camundongos Endogâmicos C57BL , Fosfoproteínas/genética , Progesterona/metabolismo , Receptores do LH/genética , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Testosterona/sangue , Testosterona/metabolismo
8.
Int J Mol Sci ; 20(15)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387263

RESUMO

In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects.


Assuntos
Endométrio/metabolismo , Estrogênios/metabolismo , Progesterona/metabolismo , Transdução de Sinais , Animais , Endometriose/tratamento farmacológico , Endometriose/etiologia , Endometriose/metabolismo , Feminino , Hormônios/metabolismo , Hormônios/uso terapêutico , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Esteroides/metabolismo
9.
Hypertension ; 74(3): 678-686, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327274

RESUMO

Compelling clinical evidence indicates that obesity and its associated metabolic abnormalities supersede the protective effects of female sex-hormones and predisposes premenopausal women to cardiovascular disease. The underlying mechanisms remain poorly defined; however, recent studies have implicated overactivation of the aldosterone-MR (mineralocorticoid receptor) axis as a cause of sex-specific cardiovascular risk in obese females. Experimental evidence indicates that the MR on endothelial cells contributes to obesity-associated, leptin-induced endothelial dysfunction in female experimental models, however, the vascular-specific mechanisms via which females are predisposed to heightened endothelial MR activation remain unknown. Therefore, we hypothesized that endogenous expression of endothelial MR is higher in females than males, which predisposes them to obesity-associated, leptin-mediated endothelial dysfunction. We found that endothelial MR expression is higher in blood vessels from female mice and humans compared with those of males, and further, that PrR (progesterone receptor) activation in endothelial cells is the driving mechanism for sex-dependent increases in endothelial MR expression in females. In addition, we show that genetic deletion of either the endothelial MR or PrR in female mice prevents leptin-induced endothelial dysfunction, providing direct evidence that interaction between the PrR and MR mediates obesity-associated endothelial impairment in females. Collectively, these novel findings suggest that progesterone drives sex-differences in endothelial MR expression and predisposes female mice to leptin-induced endothelial dysfunction, which indicates that MR antagonists may be a promising sex-specific therapy to reduce the risk of cardiovascular diseases in obese premenopausal women.


Assuntos
Endotélio Vascular/patologia , Regulação da Expressão Gênica , Obesidade/fisiopatologia , Progesterona/metabolismo , Receptores de Mineralocorticoides/genética , Animais , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Feminino , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Obesidade/genética , Distribuição Aleatória , Medição de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Regulação para Cima
10.
Gen Comp Endocrinol ; 282: 113221, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301283

RESUMO

Progesterone has received substantial attention for the essential role it plays in establishing and maintaining pregnancy in placental vertebrates. Despite the prevalence of progesterone during development, relatively little is known about how embryos respond to progesterone. This is true of placental vertebrates as well as egg-laying vertebrates where levels of progesterone in the yolk tend to be higher than most other steroids in the yolk. Bird eggs provide an opportunity to investigate the effects of progesterone on embryonic development because progesterone can be easily manipulated without any confounding effects on maternal physiology. To understand how progesterone might influence embryonic development, it is important to characterize the metabolic fate of progesterone given its potential to be converted to a wide range of steroids. We investigated the metabolic fate of tritiated progesterone over the first four days of development using chicken eggs (Gallus gallus) and identified 5ß-pregnanedione as the primary metabolite during this period. After only one day of development, 5ß-pregnanedione could be detected within the yolk. Levels of 5ß-pregnanedione in both the yolk and albumen tended to rise early in development but conjugated metabolites began to accumulate towards the end of our sampling period. Additionally, in vitro assays using embryo homogenates collected after 72 h of development demonstrated that embryos were capable of carrying out the conversion of progesterone to 5ß-pregnanedione. Overall these results have important implications for deciphering the mechanisms through which yolk progesterone might influence embryonic development. Effects could arise via progesterone receptors or receptors capable of binding 5ß-pregnanedione but we found no evidence that progesterone is serving as a precursor for androgen or estrogen production.


Assuntos
Galinhas/metabolismo , Desenvolvimento Embrionário , Pregnanodionas/metabolismo , Progesterona/metabolismo , Animais , Embrião de Galinha , Gema de Ovo/metabolismo , Feminino , Metaboloma , Gravidez , Fatores de Tempo
11.
BMC Womens Health ; 19(1): 92, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288815

RESUMO

BACKGROUND: Uterine Fibroids (UFs) growth is ovarian steroid-dependent. Previous studies have shown that estrogen and progesterone play an important role in UF development. However, the mechanism underlying progesterone induced UF pathogenesis is largely unknown. In this study, we determined the expression of progesterone receptor and compared the expression level of progesterone-regulated genes (PRGs) in human myometrial cells from normal uteri (MyoN) versus uteri with UFs (MyoF) in response to progesterone. METHODS: Primary human myometrial cells were isolated from premenopausal patients with structurally normal uteri (PrMyoN). Primary human myometrial cells were also isolated from uterus with UFs (PrMyoF). Isolated tissues were excised at least 2 cm from the closest UFs lesion(s). Progesterone receptor (PR) expression was assessed using Western blot (WB). Expression levels of 15 PRGs were measured by qRT-PCR in PrMyoN and PrMyoF cells in the presence or absence of progesterone. RESULTS: WB analysis revealed higher expression levels of PR in PrMyoF cells as compared to PrMyoN cells. Furthermore, we compared the expression patterns of 15 UF-related PRGs in PrMyoN and PrMyoF primary cells in response to progesterone hormone treatment. Our studies demonstrated that five PRGs including Bcl2, FOXO1A, SCGB2A2, CYP26a1 and MMP11 exhibited significant progesterone-hyper-responsiveness in human PrMyoF cells as compared to PrMyoN cells (P < 0.05). Another seven PRGs, including CIDEC, CANP6, ADHL5, ALDHA1, MT1E, KIK6, HHI showed gain in repression in response to progesterone treatment (P > 0.05). Importantly, these genes play crucial roles in cell proliferation, apoptosis, cell cycle, tissue remodeling and tumorigenesis in the development of UFs. CONCLUSION: These data support the idea that progesterone acts as contributing mechanism in the origin of UFs. Identification and analysis of these PRGs will help to further understand the role of progesterone in UF development.


Assuntos
Leiomioma/metabolismo , Miométrio/metabolismo , Progesterona/metabolismo , Receptores de Progesterona/metabolismo , Feminino , Expressão Gênica , Humanos , Leiomioma/patologia , Miométrio/citologia , Fatores de Risco , Útero/citologia
12.
Animal ; 13(S1): s11-s19, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31280748

RESUMO

Milk production by the sow is a major factor limiting the growth and survival of her litter. Understanding the process of morphogenesis of the sow's mammary gland and the factors that regulate mammary development are important for designing successful management tools that may enhance milk production. Primordia of the mammary glands are first observable in the porcine embryo at approximately 23 days of gestation. The glands then progress through a series of morphologically distinct developmental stages such that, at birth, each mammary gland is composed of the teat, an organized fat pad and two separate lactiferous ducts each with a few ducts branching into the fat pad. The glands continue to grow slowly until about 90 days of age when the rate of growth increases significantly. The increased rate of mammary gland growth coincides with the appearance of large ovarian follicles and an increase in circulating estrogen. After puberty, the continued growth of the gland and elongation and branching of the duct system into the fat pad takes place in response to the elevated levels of estrogen occurring as part of the estrous cycles. After conception, parenchymal mass of each gland increases slowly during early pregnancy and then grows increasingly rapidly during the final trimester. This growth is in response to estrogen, progesterone, prolactin and relaxin. Lobuloalveolar development occurs primarily during late pregnancy. By parturition, the fat pad of the mammary gland has been replaced by colostrum-secreting epithelial cells that line the lumen of the alveoli, lobules and small ducts. All mammary glands develop during pregnancy, however, the extent of development is dependent on the location of the mammary gland on the sow's underline. The mammary glands undergo significant functional differentiation immediately before and after farrowing with the formation of colostrum and the transition through the stages of lactogenesis. Further growth of the glands during lactation is stimulated by milk removal. Individual glands may grow or transiently regress in response to the intensity of suckling during the initial days postpartum. Attempts to enhance milk production by manipulation of mammary development at stages before lactation generally have met with limited success. A more in depth understanding of the processes regulating porcine mammary gland morphogenesis at all stages of development is needed to make further progress.


Assuntos
Colostro/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Leite/metabolismo , Suínos/crescimento & desenvolvimento , Animais , Células Epiteliais/metabolismo , Estrogênios/metabolismo , Ciclo Estral , Feminino , Desenvolvimento Fetal , Lactação , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/fisiologia , Parto , Gravidez , Progesterona/metabolismo , Prolactina/metabolismo , Suínos/embriologia , Suínos/fisiologia
13.
Animal ; 13(S1): s4-s10, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31280752

RESUMO

Historically, pre-pubertal development of the bovine mammary gland (MG) has received little attention compared to later development. Recent evidence suggests not only that this period represents a very active time in the development of the MG but also that the first 90 days of life can partially dictate future productivity of the lactating cow. The MG, often considered quiescent during early life (first 3 months), is now known to increase in size by over 60-fold in the same period. The importance of sex steroids in MG development is well classified, but a complex signaling network exists among estrogen, progesterone and other growth factors and hormones. Complicating our understanding of this developmental period further is the discovery that pre-weaning nutrition of the calf not only influences the growth of the mammary parenchyma but may also alter the way in which it responds to mammogenic stimuli. Recent data suggest that feeding calves a higher plane of nutrition improves the ability of the mammary epithelium to respond to estradiol and also alters the way in which the mammary parenchyma and fat pad communicate. It is clear that early life nutrition, although able to influence the MG, is still poorly understood mechanistically. For example, additional evidence suggests that increased feeding rates in early life alter the morphology of myoepithelial cells in the mammary epithelium. Further data have also suggested a role for other cell types, such as immune cells, in the penetration of the mammary parenchyma into the fat pad during the early life development of the MG suggesting that mammary development is not only controlled by the local tissue population (parenchyma and fat pad) but perhaps systemically by other tissue types (i.e., immune system). Understanding the roles of these various stimuli and signaling pathways as they relate to the development of the MG in early life may hold the key to unlocking the potential for the optimal development of this crucial organ and, in turn, may lead to improvements in other phases of mammary development and milk yield potential.


Assuntos
Bovinos/crescimento & desenvolvimento , Hormônios Esteroides Gonadais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Leite/metabolismo , Tecido Adiposo/metabolismo , Animais , Bovinos/fisiologia , Células Epiteliais/metabolismo , Estradiol/metabolismo , Estrogênios/metabolismo , Feminino , Lactação , Glândulas Mamárias Animais/fisiologia , Estado Nutricional , Progesterona/metabolismo , Desmame
14.
Exp Parasitol ; 204: 107721, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288023

RESUMO

BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan able to infect humans and it is common in pregnant women. During pregnancy and lactation, there are changes in the concentration of 17ß-estradiol (E2), progesterone (Prg), and prolactin (PRL). It is known that a proinflamatory response reduces the susceptibility to be infected, and this response may change according to hormonal impairment. Monocytes and macrophages are the main barrier against many intracellular microorganisms, due to their ability to produce cytokines. The aim of this work was to determine the effect of E2, progesterone, and PRL on the infective capacity of T. gondii, proinflamatory immune response modulation and the expression of hormonal receptors on THP-1 cell stimulated with T. gondii. METHODS: The THP-1 cells were infected with 1500 T. gondii tachyzoites, of RH strain. Stimuli were conducted with recombinant PRL (200 ng/mL), E2 (40 nM) y Prg (40 nM). MTT assays were performed to evaluate cellular viability. Western blot assays were carried out to evaluate the expression of the hormonal receptors (PRLR, ERα, and ERß). Cytokines produced were measured with a magnetic bead kit directed to 17 cytokines. RESULTS: Stimuli with E2 and Prg increased T. gondii infection in monocytes after 48 h; however, no differences in infection were observed in PRL stimulus. The E2 decreased the secretion of IL-12 and IL-1ß and PRL did not modify the production of these cytokines in THP-1 cells stimulated with T. gondii; however, both hormones increased the production of IL-10. Besides, PRL augmented the production of IL-4 and IL-13. In contrast, Prg reduced these cytokines. Our results show that T. gondii induces the expression of ERα and ERß and lowers PRLR. The hormones modify the expression of the receptors of other hormones: Prg decreases PRLR, ERß and increases ERα; E2 diminishes PRLR; and PRL decreases ERα and ERß expression. CONCLUSION: The hormones can increase T. gondii infection and could be mediating an anti-inflammatory response in THP-1 cells. T. gondii induces changes in the expression of hormonal receptors.


Assuntos
Citocinas/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Receptores da Prolactina/metabolismo , Células THP-1/metabolismo , Toxoplasma/fisiologia , Animais , Corantes , Estradiol/metabolismo , Feminino , Humanos , Camundongos , Progesterona/metabolismo , Prolactina/metabolismo , Isoformas de Proteínas/metabolismo , Células THP-1/imunologia , Células THP-1/parasitologia , Sais de Tetrazólio , Tiazóis , Toxoplasma/crescimento & desenvolvimento
15.
Eur J Pharmacol ; 860: 172560, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31344364

RESUMO

Plants, fruits, and vegetables containing the bioflavonoid quercetin are widely used in food, beverages, and medicines; however, the effects of quercetin on reproductive processes and the possible mechanisms of quercetin action require extensive investigation. The aim of our study was to examine the direct effects of quercetin on basic ovarian cell functions and their response to follicle-stimulating hormone (FSH) and insulin-like growth factor I (IGF-I), known hormonal stimulators of reproduction. We analyzed the effects of quercetin alone (0, 1, 10, and 100 ng/ml) on cultured porcine ovarian granulosa cells or isolated ovarian follicles; or of quercetin (10 ng/ml) in combination with FSH (0, 0.01, 0.1, or 1 IU/ml) or IGF-I (0, 1, 10, or 100 ng/ml) on cultured porcine granulosa cells. The expression of proliferative (PCNA, cyclin B1) and apoptotic (BAX) markers, as well as markers for release of progesterone (P4), testosterone (T), and leptin (L), were measured by quantitative immunocytochemistry, Western immunoblotting, RT-qPCR, and EIA/RIA. Addition of quercetin reduced the accumulation of PCNA and cyclin B1, as well as their transcript levels, promoted the accumulation of BAX, decreased the release of P4 and L, and increased the release of T in cultured granulosa cells. In ovarian follicles, quercetin reduced the levels of both P4 and T. Exposure to FSH stimulated PCNA and decreased BAX accumulation, and increased the release of P4, T, and L. Quercetin inhibited and even reversed the effects of FSH. Like FSH, IGF-I also promoted granulosa cell proliferation and suppressed apoptosis. Quercetin did not modify IGF-I effects. These data suggest that the plant molecule quercetin can directly down-regulate basal ovarian cell functions (proliferation, apoptosis, and release of ovarian steroid and peptide hormones) and their response to the stimulatory activity of the upstream hormonal stimulator FSH.


Assuntos
Hormônio Foliculoestimulante/farmacologia , Células da Granulosa/citologia , Células da Granulosa/efeitos dos fármacos , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina B1/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Leptina/metabolismo , Progesterona/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , RNA Mensageiro/genética , Suínos , Testosterona/metabolismo
16.
Int Immunopharmacol ; 74: 105669, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176046

RESUMO

Neuroinflammation and autophagy dysfunction are known to be involved in the pathological procession of Alzheimer's disease (AD). Progesterone (PG), neuroactive steroids, exerts a characteristic neuroprotective function in improving AD syndrome. The NOD-like receptor pyrin 3 (NLRP3)-Caspase-1 inflammasome has specific relevance to AD pathological procession. However, the exact role of PG in regulating NLRP3-Caspase-1 inflammasome remains to be elucidated. We demonstrated Aß up-regulated IL-1ß expression in astrocytes by activating NLRP3-Caspase-1 inflammasome. However, pharmacological activation of autophagy by Rapamycin (RAPA) efficiently suppressed Aß-, lipopolysaccharides (LPS)-induced IL-1ß expression via regulating NLRP3-Caspase-1 inflammasome in astrocytes. Remarkably, PG significantly inhibited Aß-induced NLRP3-Caspase-1 inflammasome activation. Autophagy inhibitor 3-MA blocked the protective effects of PG in mediating NLRP3 inflammasome and IL-1ß processing. Taken together, our observations suggest that autophagy-lysosome pathway is one specific molecular mechanism in regulating Aß-induced NLRP3-Caspase-1 inflammasome activation in astrocytes, particularly uncover the potential neuroprotection of PG in regulating upstream signaling leading to the sequence events of neuroinflammation. That neuroprotective mechanism of PG in regulating NLRP3-Caspase-1 inflammasome can be a potential therapeutic target for ameliorating the pathological procession of AD.


Assuntos
Peptídeos beta-Amiloides , Astrócitos/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroproteção , Progesterona/metabolismo , Animais , Autofagia , Células Cultivadas , Interleucina-1beta/metabolismo , Camundongos
17.
Toxicol In Vitro ; 60: 272-280, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195090

RESUMO

Epidemiological studies have shown strong deterioration in male reproductive health globally due to compromised testosterone production leading to altered spermatogenesis and poor sperm quality. However, the effects and mechanisms through which mycotoxins and persistent organochloride pesticides contribute to poor reproductive health in males remain unclear. The effects of single and binary combinations of ochratoxin A, deoxynivalenol, zearalenone, alpha-zearalenol, beta-zearalenol and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane on testicular steroidogenesis were evaluated using the MA-10 Leydig cell line after 48 h of exposure. Zearalenone exposure, especially at 16 µM, had a stimulatory effect on progesterone secretion (4.7 ±â€¯0.48 ng/mL compared to 0.60 ±â€¯0.07 ng/mL in control), but inhibited testosterone production after 48 h compared to the solvent control. Ochratoxin A treatment significantly increased both progesterone and testosterone levels. Combination of alpha-zearalenol with beta-zearalenol showed a synergistic stimulation of progesterone hormone level at 1 and 8 µM. The results presented here show that the MA-10 Leydig cell line is a useful model for assessing the effects of xenoestrogens on testicular steroidogenesis. In addition, the inhibitory effects of zearalenone, alpha-zearalenol and beta-zearalenol on testosterone production was enhanced by co-exposure with 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane, further compounding the threat posed by these mycotoxins to male reproductive health.


Assuntos
DDT/toxicidade , Hidrocarbonetos Clorados/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Micotoxinas/toxicidade , Praguicidas/toxicidade , Progesterona/metabolismo , Testosterona/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células Intersticiais do Testículo/metabolismo , Masculino
18.
Nat Commun ; 10(1): 2851, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253786

RESUMO

Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structure and function are unknown. Here we show that neuronal chromatin organization in the female ventral hippocampus of mouse fluctuates with the oestrous cycle. We find chromatin organizational changes associated with the transcriptional activity of genes important for neuronal function and behaviour. We link these chromatin dynamics to variation in anxiety-related behaviour and brain structure. Our findings implicate an immediate-early gene product, Egr1, as part of the mechanism mediating oestrous cycle-dependent chromatin and transcriptional changes. This study reveals extreme, sex-specific dynamism of the neuronal epigenome, and establishes a foundation for the development of sex-specific treatments for disorders such as anxiety and depression.


Assuntos
Encéfalo/fisiologia , Cromatina/fisiologia , Ciclo Estral/fisiologia , Neurônios/fisiologia , Animais , Comportamento Animal , Encéfalo/citologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Epigenômica , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Progesterona/metabolismo , Ligação Proteica , RNA/genética , RNA/metabolismo
19.
Poult Sci ; 98(11): 6063-6070, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31149725

RESUMO

Egg production in different goose breeds vary significantly, which is related with the physiology of reproduction. However, the knowledge of physiology of goose reproduction is not well documented. In the present study, the 3 breeds with significantly different egg production were selected to investigate the histological characteristics of follicles and reproductive hormone secretion during follicle development, which included Carlos geese (Anser anser), Zhejiang geese (Anser cygnoides), and Yangzhou geese (Anser cygnoides). The results indicated that there were significant differences in the morphology of ovary and follicles among different goose breeds. The mode of hierarchical follicles in Yangzhou geese was 5, and those were 3 and 4 in Zhejiang and Carlos geese, respectively. The numbers of prehierarchical follicles were 61 to 70, 69 to 75, and 28 to 39 in Yangzhou geese, Zhejiang geese, and Carlos geese, respectively. The thickness of granulosa layer of follicles was higher in the large yellow follicle than those in the other prehierarchical and hierarchical follicles, and Yangzhou geese were the highest among the 3 breeds. The concentration of follicle stimulating hormone (FSH) ranged from 12.17 to 28.06 U/L, and 17ß-Estradiol ranged from 27.01 to 49.39 pmol/L by the enzyme-linked immuno sorbent assay. The level of FSH of Yangzhou geese reached to the highest in the hierarchical follicle (F1), while the other 2 geese did not show the similar feature. In addition, the level of luteinizing hormone (LH) and progesterone (PROG) in the prehierarchical follicles of Yangzhou geese was higher than those in Carlos and Zhejiang geese. In summary, the difference of histological characteristics of follicles and reproductive hormone in different goose breeds was not only reflected in the number of follicles and the thickness of the granulose cell layer, but also embodied the secretion LH and PROG. The more thickness of the granulose cell layer and high secretions of LH and PROG contributed to the development of prehierarchical follicles to hierarchical follicles, which may be due to the fact that Yangzhou geese (Anser cygnoides) has more egg production.


Assuntos
Gansos/fisiologia , Hormônios/metabolismo , Ovário/fisiologia , Reprodução/fisiologia , Animais , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/fisiologia , Hormônio Luteinizante/metabolismo , Tamanho do Órgão , Folículo Ovariano/fisiologia , Progesterona/metabolismo , Especificidade da Espécie , Fatores de Tempo
20.
Gen Comp Endocrinol ; 282: 113206, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201799

RESUMO

Measuring reproductive hormones in feces has become an important tool in the endocrine characterization of wild animals' reproduction. However, several factors may influence its success, such as fecal collection and storage techniques, knowledge of steroid hormone metabolism, the extraction procedure, immunoassay selection, inherent factors, and the distribution of steroid hormones in the feces. It is known that the distribution of these hormones in the feces is not homogeneous, and prior to the extraction of the steroidal metabolites, homogenization of the feces is recommended. Hormonal analysis is based on only a small fraction of the feces, which in theory should be representative of the total. In the case of cervids and other ruminants, feces consist of pellets. Here, the concentration of the steroid metabolites of each pellet was measured in order to evaluate the distribution of the fecal progesterone metabolites concentration in 10 pellets/fecal mass from five female Mazama gouazoubira. There were large variations in fecal progesterone metabolites concentrations between the pellets of the same feces/female, showing the following amplitude variations: Animal A: 112%; Animal B: 164%; Animal C: 115%; Animal D: 62%; Animal E: 108%. These results show the importance of adequate homogenization prior to steroid metabolite extraction.


Assuntos
Cervos/metabolismo , Fezes/química , Metaboloma , Progesterona/metabolismo , Animais , Implantes de Medicamento , Feminino , Hormônios/metabolismo , Reprodução
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