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1.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205972

RESUMO

Nowadays, most people who lead healthy lifestyles tend to use natural products as supplements, complementary medicine or alternative treatments. Honey is God's precious gift to mankind. Honey has been highly appreciated and extensively used since ancient history due to its high nutritional and therapeutic values. It is also known to enhance fertility. In the last few decades, the important role of honey in modern medicine has been acknowledged due to the large body of convincing evidence derived from extensive laboratory studies and clinical investigations. Honey has a highly complex chemical and biological composition that consists of various essential bioactive compounds, enzymes, amino and organic acids, acid phosphorylase, phytochemicals, carotenoid-like substances, vitamins and minerals. Reproductive health and fertility rates have declined in the last 30 years. Therefore, this review aimed to highlight the protective role of honey as a potential therapeutic in maintaining reproductive health. The main role of honey is to enhance fertility and treat infertility problems by acting as an alternative to hormone replacement therapy for protecting the vagina and uterus from atrophy, protecting against the toxic effects of xeno-oestrogenic agents on female reproductive functions and helping in the treatment of gynaecological disorders, such as vulvovaginal candidiasis infection, that affect women's lives.


Assuntos
Fertilidade/efeitos dos fármacos , Mel/análise , Substâncias Protetoras/farmacologia , Produtos Biológicos/farmacologia , Terapias Complementares , Humanos , Valor Nutritivo , Saúde Reprodutiva
2.
Molecules ; 26(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808281

RESUMO

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/administração & dosagem , Fertilidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Resveratrol/administração & dosagem , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
3.
Molecules ; 26(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802807

RESUMO

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 µM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.


Assuntos
Carotenoides/farmacologia , Fertilidade/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Testículo/efeitos dos fármacos , Vitamina A/análogos & derivados , Animais , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Carotenoides/uso terapêutico , Catalase/metabolismo , Células Cultivadas , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Fertilidade/efeitos da radiação , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Puberdade/efeitos da radiação , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/efeitos da radiação , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Testículo/efeitos da radiação , Regulação para Cima , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Raios X
4.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923359

RESUMO

Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.


Assuntos
Fármacos para a Fertilidade Masculina/química , Fertilidade/efeitos dos fármacos , Polifenóis/química , Resveratrol/química , Arachis/química , Dieta Mediterrânea , Fertilidade/fisiologia , Fármacos para a Fertilidade Masculina/uso terapêutico , Frutas/química , Humanos , Masculino , Polifenóis/uso terapêutico , Resveratrol/uso terapêutico , Espermatozoides/efeitos dos fármacos , Vitis/química , Vinho
5.
Nat Commun ; 12(1): 2450, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893301

RESUMO

Infertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.


Assuntos
Fertilidade/fisiologia , Ligante RANK/metabolismo , Análise do Sêmen/métodos , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Animais , Hormônio Antimülleriano/sangue , Hormônio Antimülleriano/metabolismo , Denosumab/farmacologia , Fertilidade/efeitos dos fármacos , Humanos , Inibinas/antagonistas & inibidores , Inibinas/sangue , Inibinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Osteoprotegerina/farmacologia , Ligante RANK/antagonistas & inibidores , Ligante RANK/genética , Sêmen/efeitos dos fármacos , Sêmen/metabolismo , Células de Sertoli/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos
6.
Parasitol Res ; 120(6): 2263-2268, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33835244

RESUMO

The insecticide resistance in Triatoma infestans (Klug, 1834) was detected in different areas of its geographical distribution. The mechanisms of resistance involved can affect different biological processes in addition to toxicological ones. Previous studies showed that reproductive efficiency was modified in resistant females compared to susceptible ones. The objective of this study was to compare the autogenic capacity and subsequent reproductive potential between deltamethrin-resistant and susceptible T. infestans. For each toxicological phenotype, pairs were formed between unfed adult females and recently fed adult male, which were separated after confirming copulation. Females were observed weekly until death, and reproductive parameters (initiation of mating, initiation of oviposition, fecundity, fertility and period between mating and initiation of oviposition) were recorded. Females from both toxicological phenotypes showed autogenic capacity. However, a lower proportion of deltamethrin-resistant unfed females laid eggs. Autogenic females showed a higher nutritional status than non-autogenic ones. No other differences in reproductive parameters were found between resistant and susceptible autogenic females. The possible mechanisms underlying the differences observed and their consequences on the spread of resistance are discussed. This is the first report describing the effect of pyrethroid resistance on T. infestans autogeny.


Assuntos
Resistência a Inseticidas , Inseticidas/farmacologia , Nitrilas/farmacologia , Piretrinas/farmacologia , Triatoma/efeitos dos fármacos , Animais , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Oviposição/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Triatoma/genética , Triatoma/fisiologia
7.
Basic Clin Pharmacol Toxicol ; 128(5): 635-641, 2021 May.
Artigo em Inglês | MEDLINE | ID: covidwho-1132864

RESUMO

Opioids cover a broad class of natural, synthetic and semi-synthetic drugs that act on opioid receptors to produce powerful analgesic effects. Rates of opioid use and opioid agonist maintenance treatment have increased substantially in recent years, particularly among women. Trends and outcomes of opioids use on fertility, pregnancy and breastfeeding, and longer-term child developmental outcomes have not been well-described. Here, we review the existing literature on the health effects of opioid use on female fertility, pregnancy, breastmilk and the exposed infant. We find that the current literature is primarily concentrated on the impact of opioid use in pregnancy and neonatal outcomes, with little exploration of effects on fertility. Studies are limited in number, some with small sample sizes, and many are hampered by methodological challenges related to confounding and other potential biases. Opioid use is becoming more prevalent due to environmental pressures such as COVID-19. More research is needed to better elucidate its effects on reproductive health among younger women and support the development of evidence-based recommendations for safe prescription practices and public health messaging.


Assuntos
Aleitamento Materno , Fertilidade/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Padrões de Prática Médica , Complicações na Gravidez , COVID-19/epidemiologia , Feminino , Humanos , Recém-Nascido , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Prevalência , SARS-CoV-2
8.
Res Vet Sci ; 136: 360-368, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33773392

RESUMO

In vitro and in vivo assays were conducted to investigate the effects of trans-resveratrol (RVT) on liquid-extended boar semen during 72 h of storage at 17 °C. Thirty-six ejaculates were collected from six boars, evaluated, and extended. RVT was then added at the indicated treatment concentration (0, 0.01, 0.1 or 1 mM), and the ejaculates were cooled to 17 °C and evaluated at 0, 24, 48, and 72 h. Samples were evaluated for sperm motility, kinetics, plasma and acrosome integrity, mitochondrial membrane potential, anion superoxide levels, lipoperoxidation, and antioxidant enzyme activity. In the follow-up experiment, twenty-eight gilts were fixed-time inseminated with 0 or 0.01 mM RVT liquid-extended boar semen. After five days, they were slaughtered, and their reproductive tracts were recovered. The embryos were collected, and the pregnancy, fertility, and viable embryo rates were calculated. In the in vitro assays, total motility, plasma and acrosome membrane integrity, mitochondrial membrane potential, anion superoxide levels, and lipoperoxidation did not change at any of the evaluation times with the use of RVT up to 0.01 mM. RVT decreased SOD activity without changes in GPx. RVT used at 1 mM showed harmful effects for almost all evaluated parameters. For the in vivo assay, the same pregnancy and fertility rates were observed for both groups, while the viable embryo rate was three-fold lower in the 0.01 mM group than in the 0 mM group. The results showed a dichotomous effect of RVT; a low concentration was not harmful in vitro but was catastrophic for embryo viability.


Assuntos
Fertilidade/efeitos dos fármacos , Resveratrol/farmacologia , Preservação do Sêmen/veterinária , Sêmen/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Suínos , Acrossomo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Feminino , Inseminação Artificial/veterinária , Masculino , Soluções para Preservação de Órgãos/farmacologia , Gravidez , Análise do Sêmen/veterinária , Preservação do Sêmen/métodos , Motilidade Espermática/efeitos dos fármacos , Superóxidos
9.
Basic Clin Pharmacol Toxicol ; 128(5): 635-641, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33650271

RESUMO

Opioids cover a broad class of natural, synthetic and semi-synthetic drugs that act on opioid receptors to produce powerful analgesic effects. Rates of opioid use and opioid agonist maintenance treatment have increased substantially in recent years, particularly among women. Trends and outcomes of opioids use on fertility, pregnancy and breastfeeding, and longer-term child developmental outcomes have not been well-described. Here, we review the existing literature on the health effects of opioid use on female fertility, pregnancy, breastmilk and the exposed infant. We find that the current literature is primarily concentrated on the impact of opioid use in pregnancy and neonatal outcomes, with little exploration of effects on fertility. Studies are limited in number, some with small sample sizes, and many are hampered by methodological challenges related to confounding and other potential biases. Opioid use is becoming more prevalent due to environmental pressures such as COVID-19. More research is needed to better elucidate its effects on reproductive health among younger women and support the development of evidence-based recommendations for safe prescription practices and public health messaging.


Assuntos
Aleitamento Materno , Fertilidade/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Padrões de Prática Médica , Complicações na Gravidez , COVID-19/epidemiologia , Feminino , Humanos , Recém-Nascido , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Prevalência , SARS-CoV-2
10.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672019

RESUMO

Putrajeevak (Putranjiva roxburghii Wall.; synonym Drypetes roxburghii (Wall.) Hurus) seeds have been used since ancient times in the treatment of infertility in the Ayurvedic system of medicine in India. In this study, the oil component of Putrajeevak seeds (PJSO) was extracted using the supercritical fluid extraction (SCFE) method using liquid CO2 and the constituents were analyzed using gas chromatography-flame ionized detectorand high-performance thin-layer chromatography. PJSO contained trace amounts of ß-sitosterol with oleic and linoleic acids as the major fatty acid constituents. Male and female zebrafish were mutagenized with N-ethyl-N-nitrosourea (ENU) and fish that produced less than 20 viable embryos were selected for the study. SCFE oil extracts from the P. roxburghii seeds were used in this study to reverse fertility impairment. The mutant fish were fed with PJSO for a period of 14 days and the rates of fertility, conception, and fecundity were determined with wild-type healthy fish as a breeding partner. Treatment with PJSO increased the ovarian follicle count as well as the number of mature eggs, while reducing the number of ovarian cysts. Sperm count as well as sperm motility were greatly enhanced in the ENU-mutagenized male zebrafish when treated with PJSO. The results obtained in this study demonstrate the effectiveness of P. roxburghii seed oil in reversing impaired fertility in both male and female zebrafish models.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Euphorbiaceae/química , Fertilidade/fisiologia , Sementes/química , Peixe-Zebra/fisiologia , Animais , Modelos Animais de Doenças , Ácidos Graxos/análise , Ácidos Graxos/química , Feminino , Fertilidade/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Ovário/fisiologia , Óvulo/fisiologia , Pelve/patologia , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Óleos Vegetais/uso terapêutico , Sitosteroides/análise , Sitosteroides/química , Testículo/efeitos dos fármacos , Testículo/patologia
11.
Expert Opin Drug Saf ; 20(5): 503-521, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33600273

RESUMO

INTRODUCTION: As the population of young cancer survivors is increasing and a trend toward postponing pregnancy later in life is reported, more efforts are focused toward understanding treatment-induced sequelae, in particular, the effects of cancer and/or treatment on fertility. AREA COVERED: Whereas the fertility risk of cytotoxic agents for both men and women is well recognized, the impact of molecular-targeted therapy (MTT) on fertility parameters, their teratogenic potential and pregnancy outcome/management in case of an accidental exposure are not established. We update available clinical data on the impact of new MTTs on fertility in both sexes, their potential teratogenic effects and the outcome of pregnancy during accidental exposure. Agents are categorized by class and the potential relevance of their target signaling pathways to gonadal maturation. EXPERT OPINION: The majority of MTTs have worrying preclinical data discouraging their use during pregnancy and reinforcing the idea that they can induce impairment in gonadal function. However, it does not mean that all MTTs result in permanent infertility and that they should be completely avoided during pregnancy. The current review provides a critical evaluation on the most commonly used MTTs, offering a possible guide for clinicians.


Assuntos
Antineoplásicos/efeitos adversos , Fertilidade/efeitos dos fármacos , Terapia de Alvo Molecular/efeitos adversos , Animais , Antineoplásicos/administração & dosagem , Sobreviventes de Câncer , Feminino , Humanos , Masculino , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Resultado da Gravidez
12.
Poult Sci ; 100(2): 1221-1238, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518080

RESUMO

High levels of polyunsaturated fatty acids in avian sperm cause more susceptibility to lipid peroxidation. Aging in roosters reduces the antioxidant capacity of sperm and thus fertility. The purpose of this study was to investigate the effects of different levels of alpha-lipoic acid (ALA) as a feed supplement to improve the semen quality and fertility parameters of aged broiler breeder roosters and identification of its most effective level. A total of forty-two roosters at 45 wk of age were randomly assigned to 7 treatments (0, 15, 40, 70, 95, 120, and 145 mg ALA/bird per day) for 8 wk. Semen parameters and body weight were assessed biweekly, and testosterone plasma levels were determined in the 8th wk of the experimental period. Artificial insemination was performed at the end of the experiment to evaluate the fertility potential. The dietary administration of ALA had no significant effects on body weight, semen volume, average path velocity, linearity, straightness, wobble, the amplitude of lateral head displacement, beat-cross frequency, sperm concentration, morphology, plasma testosterone level, fertility, or hatchability (P > 0.05). Alpha-lipoic acid supplementations resulted in a significant decrease in seminal malondialdehyde concentration and immotile (type D) sperms (P < 0.05). The total motility, progressive motility (types A + type B sperms), curvilinear velocity, straight-line velocity, viability, and membrane integrity of sperm improved with ALA dietary supplementations (P < 0.05). With increasing ALA levels, improvement in semen parameters had an incremental trend until the level of 95 mg ALA. Thus, 95 mg dietary ALA as an antioxidant supplement can improve semen quality of aging breeder roosters while higher doses resulted in no further improvement.


Assuntos
Envelhecimento/fisiologia , Galinhas/fisiologia , Fertilidade/efeitos dos fármacos , Sêmen/fisiologia , Ácido Tióctico/administração & dosagem , Ração Animal/análise , Animais , Peso Corporal/fisiologia , Suplementos Nutricionais , Feminino , Fertilidade/fisiologia , Inseminação Artificial/veterinária , Masculino , Sêmen/química , Análise do Sêmen/veterinária , Motilidade Espermática , Espermatozoides/fisiologia
13.
Ecotoxicol Environ Saf ; 210: 111875, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454577

RESUMO

Coccinella septempunctata (ladybird) is one of the foremost natural predators that feed on aphids. Thus, C. septempunctata serves as an effective biological control agent in integrated pest management (IPM) programs. To supplement the activity of biological control agents, IPM programs often incorporate chemical pesticides to bolster crop protection. To evaluate the effects of a potent insecticide, tolfenpyrad, on C. septempunctata, we tested the sublethal effects of tolfenpyrad on all developmental stages of the life cycle of C. septempunctata and its effects on the next generation. For sublethal testing of the parent generation, the LR50 of tolfenpyrad for C. septempunctata was determined to range from 1.04 to 8.43 g a.i. /hm2 within a set exposure period, while the hazard quotient (HQ) values were above our threshold value of 2 during the entire observation period. These data indicated a potential toxicity risk from tolfenpyrad exposure. The no observed effect application rates (NOERs) of tolfenpyrad on parents (F0) were determined for survival (0.485 g a.i. /hm2), developmental time of pupation (0.242 g a.i. /hm2), and fecundity (0.485 g a.i. /hm2). Application of sublethal doses to unexposed progeny (F1) of exposed parents, prolonged the L1 (1st instar of larvae) and L2 (2nd instar of larvae) stage, while the total longevity, intrinsic rate of increase (r), finite rate of increase (γ), net reproductive rate (R0), and mean generation time (T) were significantly reduced. These results demonstrated the negative influence of sublethal concentrations of tolfenpyrad on C. septempunctata and its persistent effects on subsequent generations.


Assuntos
Besouros/efeitos dos fármacos , Inseticidas/toxicidade , Pirazóis/toxicidade , Animais , Besouros/fisiologia , Feminino , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/fisiologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Controle de Pragas , Reprodução/efeitos dos fármacos
14.
Parasit Vectors ; 14(1): 9, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407825

RESUMO

BACKGROUND: With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Blood containing the antihelminthic drug ivermectin has been shown to have lethal and sub-lethal effects on mosquitoes. Almost all work to date has been on Anopheles spp., but impacts on other anthropophagic vectors could provide new options for their control, or additional value to anti-malarial ivermectin programmes. METHODS: Using dose-response assays, we evaluated the effects of ivermectin delivered by membrane feeding on daily mortality (up to 14 days post-blood feed) and fecundity of an Indian strain of Aedes aegypti. RESULTS: The 7-day lethal concentration of ivermectin required to kill 50% of adult mosquitoes was calculated to be 178.6 ng/ml (95% confidence intervals 142.3-218.4) for Ae. aegypti, which is much higher than that recorded for Anopheles spp. in any previous study. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul). CONCLUSION: Our results suggest that levels of ivermectin present in human blood at current dosing regimes in mass drug administration campaigns, or even those in a recent higher-dose anti-malaria trial, are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels of ivermectin in livestock blood is also unlikely to be an effective option for its control. However, other potential toxic impacts of ivermectin metabolites, accumulation in tissues, sublethal effects on behaviour, or antiviral action might increase the efficacy of ivermectin against Ae. aegypti and the arboviral diseases it transmits, and require further investigation.


Assuntos
Aedes/efeitos dos fármacos , Infecções por Arbovirus/prevenção & controle , Ivermectina/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Infecções por Arbovirus/transmissão , Fertilidade/efeitos dos fármacos , Ivermectina/administração & dosagem , Mortalidade , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos
15.
Toxicol Appl Pharmacol ; 413: 115409, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476676

RESUMO

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e. across the placenta and/or by breastfeeding) is underestimated, although it can be assumed to be a cause of idiopathic female infertility. Therefore, we hypothesised the deleterious effects of exposure to BPA analogues during breastfeeding on the ovarian and oocyte quality of offspring. A 15-day exposure period of pups was designed, whilst nursing dams (N ≥ 6 per experimental group) were treated via drinking water with a low (0.2 ng/g body weight/day) or moderate (20 ng/g body weight/day) dose of bisphenol, mimicking real exposure in humans. Thereafter, female pups were bred to 60 days and oocytes were collected. Immature oocytes were used in the in-vitro maturation assay; alternatively, in-vivo-matured oocytes were isolated and used for parthenogenetic activation. Both in-vitro- and in-vivo-matured oocytes were subjected to immunostaining of spindle microtubules (α-tubulin) and demethylation of histone H3 on the lysine K27 (H3K27me2) residue. Although very low doses of both BPS and BPF did not affect the quality of ovarian histology, spindle formation and epigenetic signs were affected. Notably, in-vitro-matured oocytes were significantly sensitive to both doses of BPS and BPF. Although no significant differences in spindle-chromatin quality were identified in ovulated and in-vivo-matured oocytes, developmental competence was significantly damaged. Taken together, our mouse model provides evidence that bisphenol analogues represent a risk to human reproduction, possibly leading to idiopathic infertility in women.


Assuntos
Compostos Benzidrílicos/toxicidade , Fertilidade/efeitos dos fármacos , Infertilidade Feminina/induzido quimicamente , Lactação/metabolismo , Leite/metabolismo , Oócitos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Animais , Animais Lactentes , Compostos Benzidrílicos/metabolismo , Epigênese Genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Maturação in Vitro de Oócitos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Exposição Materna , Camundongos Endogâmicos ICR , Oócitos/metabolismo , Oócitos/patologia , Reserva Ovariana/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Fenóis/metabolismo , Gravidez , Medição de Risco , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/metabolismo , Fuso Acromático/patologia , Sulfonas/metabolismo
16.
Arch Gynecol Obstet ; 303(1): 259-268, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32852572

RESUMO

PURPOSE: To compare fertility and reproductive outcome after surgical, medical, and expectant management for tubal ectopic pregnancy (EP). METHODS: 133 of 228 patients, who were managed between January 2012 and December 2017 for a tubal EP, tried to conceive immediately after treatment: 86 out of 173 (49.7%) underwent surgical treatment; 38 (21.9%) were treated with methotrexate (MTX), and 49 (28.3%) had expectant management. Clinical data were retrieved by medical records, fertility outcomes were obtained by phone follow-up. The cumulative incidence (CI) of intrauterine clinical pregnancy (CP), miscarriage, live birth (LB), and recurrent EP, and the time between treatment and first intrauterine CP were compared between women treated with MTX, surgery and expectant management. RESULTS: The CI of intrauterine CP starting from 12 months after the EP was 65.3% for the expectant management, 55.3% for the MTX group, and 39.5% for surgery (p = 0.012). Post-hoc analysis showed expectant management having higher intrauterine CP and LB, and shorter time between treatment and first intrauterine CP compared to surgery (p < 0.05). The CI of recurrent EP was comparable between the 3 groups. The analysis stratified per ßhCG cut-off of 1745 mUI/mL and EP mass cut-off of 25 mm reported consistent results. CONCLUSIONS: Women successfully managed by expectation appear to have better reproductive outcomes compared to women who underwent surgery, with the shortest time to achieve a subsequent intrauterine CP. Therefore, if safely applicable the expectant management should be considered in the case of tubal EP. The fact that the chosen treatment was primarily guided by the ßhCG value and EP mass diameter based on the protocol, which is intrinsically related to the characteristics of the EP, represents the main limitation of the present study. Indeed, we cannot completely exclude that the observed differences between treatments are related to the EP itself instead of the treatment.


Assuntos
Fertilidade/efeitos dos fármacos , Metotrexato/uso terapêutico , Gravidez Tubária/cirurgia , Salpingectomia/métodos , Conduta Expectante , Adulto , Feminino , Humanos , Gravidez , Reprodução , Salpingostomia , Resultado do Tratamento
18.
Int J Occup Med Environ Health ; 34(1): 15-37, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33223541

RESUMO

Over the past years, many legitimate concerns have been raised about the effects of dibutyl phthalate (DBP) as an endocrine disruptor, especially on reproduction. The aim of this publication is to critically review the literature related to the developmental and reproductive toxicity of DBP in animals. Several electronic databases were systematically searched until 2019. Studies were qualified for the review if they: linked exposure to DPB with reproduction, were published in English after 1990, and were conducted on animals. In the studies of the testicular effects of DBP on experimental animals, the most common effects of exposure included reduced fertility, atrophic changes in male gonads, degenerative changes in the epididymis, as well as a reduction in sperm count and motility, cryptorchidism, hypospadias, poor sperm quality and other genital defects (decreased testicular weight, delayed spermatogenesis, Leydig cell aggregation, impaired Sertoli cell maturation, and significant inhibitions of testicular enzymes). The embryotoxic effects of DBP on laboratory animals included mainly an increase in fetal resorption and a decrease in live births. The teratogenic effects of DBP also manifest as skeletal malformations in fetuses, malformations of male gonads and other genital effects. On the basis of the literature data, it is clearly demonstrated that DBP shows anti-androgenic effects; however, there are also reports confirming its weak estrogenic effect. Additionally, lower doses cause more adverse effects than the highest dose, which is an important fact because of the widespread environmental exposure to DBP. The studies clearly confirm that DBP is an endocrine disruptor. Int J Occup Med Environ Health. 2021;34(1):15-37.


Assuntos
Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Gravidez/efeitos dos fármacos , Teratogênese/efeitos dos fármacos , Testículo/anormalidades , Testículo/efeitos dos fármacos
19.
Insect Sci ; 28(2): 430-444, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108427

RESUMO

Apolygus lucorum is the dominant pathogenic insect attacking Bacillus thuringiensis (Bt) cotton in China. Additionally, 20-hydroxyecdysone (20E) has important functions in many biological processes, including insect reproduction. Phospholipase C (PLC), which is an essential enzyme for phosphoinositide metabolism, is involved in 20E signal transduction, but its function in 20E-mediated reproduction in A. lucorum remains unclear. In this study, 20E increased AlPLCγ transcription as well as the abundance and activity of the encoded protein during molting and metamorphosis. The 20E treatment also induced the considerable accumulation of two second messengers, inositol triphosphate and diacylglycerol. The expression levels of genes encoding vitellogenin (AlVg) and soluble trehalase (AlTre-1) were similar to those of AlPLCγ, and were upregulated in response to 20E. The silencing of AlPLCγ resulted in downregulated expression of AlTre-1 and AlVg. However, the silencing of AlTre-1 and AlVg did not affect AlPLCγ expression. Moreover, the silencing of AlVg did not alter AlTre-1 expression. Furthermore, an examination of the insect specimens indicated that AlPLCγ is required for female adult reproduction, and that downregulated expression of this gene is associated with decreases in fecundity, adult longevity, and egg hatching rate as well as delayed oocyte maturation. We propose that 20E regulates AlTre-1 expression via AlPLCγ and affects Vg expression as well as ovary development to facilitate the reproductive activities of A. lucorum females.


Assuntos
Heterópteros/fisiologia , Proteínas de Insetos/genética , Fosfolipase C gama/genética , Trealase/metabolismo , Sequência de Aminoácidos , Animais , Ecdisterona/administração & dosagem , Feminino , Fertilidade/efeitos dos fármacos , Heterópteros/genética , Heterópteros/crescimento & desenvolvimento , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Fosfolipase C gama/química , Fosfolipase C gama/metabolismo , Filogenia
20.
Biomed Pharmacother ; 133: 110868, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33181455

RESUMO

Male infertility has become an important health problem that is primarily caused by testicular dysfunction with abnormal spermatogenesis. In this study, we demonstrated that the neuropeptide, substance P (SP), is essential for spermatogonia proliferation in a seminiferous tubule culture system. In addition, SP (5 nmol/kg) treatment markedly restored spermatogenesis, improved sperm quality, and increased the number of ZBTB16+ or LIN28+ undifferentiated spermatogonia as well as STRA8+ differentiated spermatogonia in a busulfan-induced non-obstructive azoospermic mouse model. Furthermore, 100 nM SP treatment in vitro significantly stimulated the proliferation of GC-1 spg cells (a spermatogonia cell line) via activation of the Erk1/2 signaling pathway. Moreover, the sperm quality and the number of spermatogonia were significantly reduced after treatment with RP67580, a selective NK-1 receptor antagonist, suggesting that SP-NK1R signaling plays an important role in spermatogenesis. Taken together, these results suggest that SP may be a potential therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.


Assuntos
Azoospermia/tratamento farmacológico , Fármacos para a Fertilidade Masculina/farmacologia , Fertilidade/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogônias/efeitos dos fármacos , Substância P/farmacologia , Animais , Apoptose/efeitos dos fármacos , Azoospermia/induzido quimicamente , Azoospermia/metabolismo , Azoospermia/fisiopatologia , Bussulfano , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores da Neurocinina-1/agonistas , Receptores da Neurocinina-1/metabolismo , Transdução de Sinais , Espermatogônias/metabolismo , Técnicas de Cultura de Tecidos
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