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1.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445797

RESUMO

Previous studies have demonstrated that endocrine disruptors (EDs) can promote the transgenerational inheritance of disease susceptibility. Among the many existing EDs, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) affects reproductive health, including in humans, following direct occupational exposure or environmental disasters, for instance the Agent Orange sprayed during the Vietnam War. Conversely, few studies have focused on TCDD multigenerational and transgenerational effects on human reproductive health, despite the high amount of evidence in animal models of such effects on male and female reproductive health that mimic human reproductive system disorders. Importantly, these studies show that paternal ancestral TCDD exposure substantially contributes to pregnancy outcome and fetal health, although pregnancy outcome is considered tightly related to the woman's health. In this work, we conducted a systematic review of the literature and a knowledge synthesis in order (i) to describe the findings obtained in rodent models concerning TCDD transgenerational effects on reproductive health and (ii) to discuss the epigenetic molecular alterations that might be involved in this process. As ancestral toxicant exposure cannot be changed in humans, identifying the crucial reproductive functions that are negatively affected by such exposure may help clinicians to preserve male and female fertility and to avoid adverse pregnancy outcomes.


Assuntos
Dibenzodioxinas Policloradas/efeitos adversos , Reprodução/efeitos dos fármacos , Animais , Exposição Ambiental/efeitos adversos , Substâncias Perigosas/efeitos adversos , Humanos , Saúde Reprodutiva
2.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445135

RESUMO

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol's family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.


Assuntos
Inositol/farmacologia , Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Parto/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Feminino , Fertilização/efeitos dos fármacos , Humanos , Gravidez , Resultado da Gravidez
3.
Toxicol Appl Pharmacol ; 426: 115639, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34256052

RESUMO

Polychlorinated biphenyls (PCBs) are endocrine disrupting chemicals with documented, though mechanistically ill-defined, reproductive toxicity. The toxicity of dioxin-like PCBs, such as PCB126, is mediated via the aryl hydrocarbon receptor (AHR) in non-ovarian tissues. The goal of this study was to examine the uterine and ovarian effects of PCB126 and test the hypothesis that the AHR is required for PCB126-induced reproductive toxicity. Female Holzman-Sprague Dawley wild type (n = 14; WT) and Ahr knock out (n = 11; AHR-/-) rats received a single intraperitoneal injection of either corn oil vehicle (5 ml/kg: WT_O and AHR-/-_O) or PCB126 (1.63 mg/kg in corn oil: WT_PCB and AHR-/-_PCB) at four weeks of age. The estrous cycle was synchronized and ovary and uterus were collected 28 days after exposure. In WT rats, PCB126 exposure reduced (P < 0.05) body and ovary weight, uterine gland number, uterine area, progesterone, 17ß-estradiol and anti-Müllerian hormone level, secondary and antral follicle and corpora lutea number but follicle stimulating hormone level increased (P < 0.05). In AHR-/- rats, PCB126 exposure increased (P ≤ 0.05) circulating luteinizing hormone level. Ovarian or uterine mRNA abundance of biotransformation, and inflammation genes were altered (P < 0.05) in WT rats due to PCB126 exposure. In AHR-/- rats, the transcriptional effects of PCB126 were restricted to reductions (P < 0.05) in three inflammatory genes. These findings support a functional role for AHR in the female reproductive tract, illustrate AHR's requirement in PCB126-induced reprotoxicity, and highlight the potential risk of dioxin-like compounds on female reproduction.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Disruptores Endócrinos/toxicidade , Bifenilos Policlorados/toxicidade , Receptores de Hidrocarboneto Arílico/deficiência , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biotransformação/genética , Peso Corporal/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Ratos Transgênicos , Receptores de Hidrocarboneto Arílico/genética , Reprodução/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/metabolismo , Útero/patologia
4.
Toxicol Appl Pharmacol ; 426: 115638, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242569

RESUMO

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.


Assuntos
Nicotina/toxicidade , Oócitos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Lactação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Troca Materno-Fetal , Mitocôndrias/efeitos dos fármacos , Oócitos/metabolismo , Gravidez , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
5.
Biomed Pharmacother ; 140: 111448, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130202

RESUMO

Isoflavones are a group of secondary metabolites found in plants belonging to the class of phytoestrogens. These, because they have a chemical structure similar to the endogenous hormone 17ß-estradiol, act as endocrine disruptors over the different development window periods. This study aimed to evaluate male and female reproductive systems' responses when exposed to isoflavones during the development window. It is characterized as a bibliographic review, built after analyzing clinical and preclinical articles indexed in English, Portuguese, and Spanish published in the last ten years. The isoflavones, aglycone or glucosides, have essential therapeutic properties in the relief of postmenopausal symptoms in women, reduce the proliferation of cancers, in addition to being antioxidants. On the other hand, they can still behave in a similar way to 17ß-estradiol, binding to hormone receptors and acting as endocrine disruptors over the gestational period until pre-puberty, negatively affecting the development of the reproductive system. The effects on reproduction are not dose-response but are influenced by the type of isoflavone and period. There are variations in the serum concentration of hormones and action on their negative feedback on the hypothalamic-pituitary-testicular axis in males. Reproductive functions are also affected by spermatogenesis, such as decreased sperm count, lower reproductive performance, reduced litter size, low sperm production, and reduced seminal vesicle size. In females, puberty is reached later, irregular estrous cycle, reduced weight of the ovary, uterus, lower serum levels of estradiol and progesterone, reduced fertility, or interrupted fertility. At the end of the analysis of the selected publications, it can be concluded that despite the beneficial therapeutic effects in the face of pathologies, the unknown consumption of doses and types of isoflavones in food can damage the development and reproduction of individuals. Therefore, further studies must be carried out to elucidate the usual safe doses of the analyzed phytoestrogen. Greater control over insertion in foods targeted at pediatric consumers should be implemented until we have adequate safety.


Assuntos
Fertilidade/efeitos dos fármacos , Isoflavonas/farmacologia , Animais , Feminino , Hormônios/sangue , Humanos , Masculino , Fitoestrógenos/farmacologia , Reprodução/efeitos dos fármacos
6.
Mutat Res Rev Mutat Res ; 787: 108345, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083036

RESUMO

The current review looks for relationships between results from biomarker studies with micronucleus and health effects related to reproduction and children. In adults, an age related increase in MN is well known as well as associations with environmental exposures especially air pollution from traffic and smoking. Literature searches in PubMED and SCOPUS were performed with the following keywords reproduction, children, micronuclei, health effects. In total 162 studies were identified with the keyword children. Concerning children and health and children and environmental exposures, the titles and abstracts of a total of 162 publications were screened for language, inclusion of data from children and selected according to a study selection chart. 9 studies were included for children and health, and 21 studies for children and environmental exposures, with 12 in buccal cells and 9 in lymphocytes. The publications were read and included in tables if data on controls was available. MN frequencies were collected for peripheral blood lymphocytes (PBLs), reticulocytes or buccal cells (BC) and reported as Mean ± SD or Median (IQR). The Mean frequency Ratio, MRi, corresponding to the MN mean for study persons divided by MN mean for control persons was stated as reported in the publication or calculated by us from the data in the publication, where possible. Our systematic analysis revealed a number of positive associations of MN frequencies as a marker of increased health risk in relation to reproduction as well as child health. The majority of studies reported with children concerns exposures of children as well as maternal exposures and newborn health with MN as a biomarker of exposure. Exposure monitoring by MN as biomarker is also reported in studies of school children however most often not related to health effects. The MRis are found in ranges from 1 to 5.5 most studies around 2. As far as MN frequencies in children and exposure are concerned, the MRis range from 0.9 to 5.5, with a range from 1.3-4.9 for lymphocytes and from 1.5 to 2.5 in buccal cells, except for two studies with no differences found between cases and controls. Only one study is available for MRi calculation in reticulocytes with the value of 2.3. These data are supporting MN as a relevant biomarker for children health. However, the data is mostly from small studies with different protocol leaving out the possibility of metanalyses and even statistical comparisons among studies. The actual risk from elevated MNs in children waits large cohort studies with pooled datasets as performed with MN measured in adults. Introduction of buccal cells as non invasive alternative to lymphocytes is increasing and as with the lymphocytes standardised protocols are recommended to enable comparative studies and metaanalyses.


Assuntos
Exposição Ambiental/efeitos adversos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Adolescente , Animais , Criança , Saúde da Criança , Monitoramento Ambiental/métodos , Feminino , Humanos , Masculino , Reprodução/efeitos dos fármacos , Reprodução/genética
7.
Toxins (Basel) ; 13(6)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073731

RESUMO

Contamination of the world's food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN's synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000-2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified.


Assuntos
Estrogênios não Esteroides/toxicidade , Reprodução/efeitos dos fármacos , Zearalenona/toxicidade , Zeranol/toxicidade , Animais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Placenta/efeitos dos fármacos , Gravidez , Útero/efeitos dos fármacos , Útero/patologia
8.
Ecotoxicol Environ Saf ; 221: 112457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175827

RESUMO

Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial economic losses worldwide. This study aimed to demonstrate the reproductive injury induced by ZEA in rodents. We conducted a rigorous meta-analysis of the related literature via PubMed, Embase, and Web of Science. The scope of the study includes the following: development of reproductive organs, serum testosterone, oestradiol, and luteinizing hormone (LH) levels; parameters of Leydig cells; and parameters of semen. In total, 19 articles were reviewed. Compared with the control group, the increased relative epididymis weight, increased serum oestradiol level, and decreased LH levels in the prenatally exposed group were observed. In pubertal and adult rodents, the relative testicular weight, serum oestradiol level, Leydig cell number, and percentage of ST (+) Leydig cells decreased under ZEA exposure. In rodents at all ages, decreased serum testosterone level, sperm concentration, sperm motility rate, and increased serum deformity rate were observed in exposed groups compared with control groups. Although subgroup analysis failed to identify a clear dose-response relationship between ZEA exposure and reproductive system damage in male rodents, we still managed to confirm that zearalenone could decrease the serum testosterone level at the dosage of 50 mg/kg*day, 1.4 mg/kg*day, and 84 mg/kg*day, of prenatal, pubertal, and mature rodents respectively; pubertal zearalenone exposure impairs the quality and quantity of sperms of rodents at the dosage of 1.4 mg/kg*day and mature zearalenone exposure has the same effect at the dosage of 84 mg/kg*day. In conclusion, we found that ZEA exposure can cause considerable damage to the reproductive system of rodents of all ages. While the exact underlying mechanism of ZEA-induced toxicity in the reproductive system remains largely unknown, the theories of oestrogen-like effects and oxidative stress damage are promising.


Assuntos
Estrogênios/toxicidade , Reprodução/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Masculino
9.
Methods Mol Biol ; 2326: 19-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097258

RESUMO

The contamination of heavy metals, a class of naturally occurring and persistent toxicants, has become a major public health concern due to increasing industrial and anthropogenic activities. The use of COPAS Biosort, a flow cytometer capable of measuring thousands of nematodes in minutes via high-throughput assays, has been widely applied in C. elegans studies for assessing toxicity of individual metals; however, such application yet to be seen for metals or other chemical mixtures. In the present protocol, we investigated toxic effects of individual metals, Cd, Pb, and Mn, as well as their binary and ternary mixtures, using nematode C. elegans. The toxic outcomes, including effects on growth, reproduction, and feeding behavior, were measured using high-throughput platform analysis (COAPS Biosort).


Assuntos
Cádmio/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Chumbo/toxicidade , Manganês/toxicidade , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Reprodução/efeitos dos fármacos , Testes de Toxicidade/métodos
10.
Methods Mol Biol ; 2326: 47-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097260

RESUMO

Drosophila melanogaster, the fruit fly, has been widely used in biological investigation as an invertebrate alternative to mammals for its various advantages compared to other model organisms, which include short life cycle, easy handling, high prolificacy, and great availability of substantial genetic information. The behavior of Drosophila melanogaster is closely related to its growth, which can reflect the physiological conditions of Drosophila. We have optimized simple and robust behavioral assays for determining the larvae survival, adult climbing ability (mobility assay), reproductive behavior, and lifespan of Drosophila. In this chapter, we present the step-by-step detailed method for studying Drosophila behavior.


Assuntos
Drosophila melanogaster/fisiologia , Animais , Bioensaio/métodos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Locomoção/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Testes de Toxicidade/métodos
11.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065597

RESUMO

Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy.


Assuntos
Didrogesterona/administração & dosagem , Fase Luteal/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Suplementos Nutricionais , Implantação do Embrião/efeitos dos fármacos , Feminino , Fertilização In Vitro/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Parto/efeitos dos fármacos , Placenta/efeitos dos fármacos , Gravidez , Taxa de Gravidez , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Técnicas de Reprodução Assistida
12.
Aquat Toxicol ; 236: 105873, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082366

RESUMO

To study the effects of exposure of fish to opioid drugs, we exposed Japanese medaka (Oryzias latipes) over a full life cycle to codeine spiked into river water at nominal concentrations of 100, 1,000 and 25,000 ng/L and to fentanyl spiked into river water at nominal concentrations of 5, 25 and 1,000 ng/L. The measured concentrations during medaka exposures were consistent with the nominal concentrations. Treatments with codeine at all test concentrations reduced the number of eggs produced by female medaka, as well as the number of mature oocytes observed histologically in the ovaries. Exposures to codeine also resulted in altered concentrations of hormones within the hypothalamic-pituitary-gonadal axis, including reduced levels of 17ß-estradiol in female medaka. Fentanyl did not affect reproduction or the levels of hormones in medaka at the concentrations tested. Monitoring of surface waters in southern Ontario, Canada downstream of wastewater treatment plants showed that the test concentrations of fentanyl and codeine were environmentally relevant. The results of this work contribute to the literature on the impacts of opioids and other drugs of abuse released into surface waters.


Assuntos
Analgésicos Opioides/toxicidade , Oryzias/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Estradiol/farmacologia , Feminino , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Ontário , Ovário/efeitos dos fármacos , Reprodução/efeitos dos fármacos
13.
Crit Rev Toxicol ; 51(4): 283-300, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949917

RESUMO

Bisphenols are common chemicals found in plastics and epoxy resins. Over the past decades, many studies have shown that bisphenol A (BPA) is a potential endocrine-disrupting chemical that may cause multisystem toxicity. However, the relative safety of BPA analogues is a controversial subject. Herein, we conducted a review of the reproductive toxicity, neurotoxicity, immunotoxicity, metabolic toxicity and gut microbiome toxicity of the BPA analogues in various species, including Caenorhabditis elegans, zebrafish, turtles, sheep, rodents, and humans. In addition, the mechanisms of action were discussed with focus on bisphenol S and bisphenol F. It was found that these BPA analogues exert their toxic effects on different organs and systems through various mechanisms including epigenetic modifications and effects on cell signaling pathways, microbiome, and metabolome in different species. More research is needed to study the relative toxicity of the lesser-known BPA analogues compared to BPA, both systemically and organ specifically, and to better define the underlying mechanisms of action, in particular, the potentials of disrupting microbiome and metabolism.


Assuntos
Compostos Benzidrílicos/toxicidade , Sistema Imunitário/efeitos dos fármacos , Fenóis/toxicidade , Animais , Disruptores Endócrinos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Reprodução/efeitos dos fármacos , Ovinos , Sulfonas , Peixe-Zebra
14.
Expert Rev Clin Pharmacol ; 14(8): 979-989, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33982647

RESUMO

STRACTBackground: Psoriatic arthritis (PsA) is the musculoskeletal manifestation of psoriatic disease, an inflammatory systemic disease with a high incidence in the reproductive years. Biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) as well as 'small molecules', are increasingly used to treat subtypes of PsA. Safety concerns exist in the field of fertility for PsA patients since the literature shows discordant results toward the influence of anti-psoriatic drugs.Areas covered: This comprehensive review critically reviews the available data on the safety of biologics and small molecules in PsA including pregnancy and lactation and men who want to father a child. TNF inhibitors (TNFi) are best studied in relation to reproduction. For other biologics and small molecules, no prospective, controlled studies are available.Expert opinion: No contraindications appear for TNFi in pregnancy, lactation, and paternal exposure. For biologics other than TNFi and small molecules, prospective controlled studies on outcomes after exposure in early and late pregnancy are urgently needed. Potential effects of all biologics on immune function, infection rates, and vaccine responses in prenatally exposed children need to be expanded. Until more data become available, small molecules should be avoided during pregnancy and breastfeeding. More reproduction-related data are expected from various national and international registries in the future.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Animais , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Lactação , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Reprodução/efeitos dos fármacos
15.
Biomed Pharmacother ; 140: 111760, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34052566

RESUMO

The global prevalence of diabetes mellitus is rapidly increasing. This disease is associated with many complications including male reproductive dysfunctions and infertility. Seahorse ( Hippocampus kuda) is a marine teleost fish well known for its beneficial effects on the reproductive system in traditional Chinese medicine books. Recently, several studies have been shown that the enzymatic hydrolysate of seahorse has multiple pharmacological activities. This study aimed to investigate the seahorse peptide hydrolysate (SH) ameliorative effects on the diabetic-induced male reproductive dysfunction in rat models. The in vivo studies were carried out with three different doses of SH (4, 8, and 20 mg/kg) and the diabetes condition was induced by administrating with streptozotocin (35 mg/kg) and fed a 40% high-fat diet. Seahorse hydrolysate (20 mg/kg) inhibited lipid peroxidation, increased antioxidant enzyme activity, and restored seminiferous tubules morphology in testis. Moreover, it improved reproductive dysfunction by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, sperm count, and motility. According to these results, we suggested that SH exhibited amelioration effects on the reproductive dysfunction.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Proteínas de Peixes , Hidrolisados de Proteína/uso terapêutico , Reprodução/efeitos dos fármacos , Smegmamorpha , Animais , Glicemia/efeitos dos fármacos , Glicemia/imunologia , Citocinas/imunologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Hidrolisados de Proteína/farmacologia , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/anormalidades , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue
16.
Toxicology ; 457: 152810, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33984407

RESUMO

With the rapid development of economic globalization and industrialization, lead (Pb), one of the most important heavy metals, has been used widely since antiquity for several purposes. In fact, its impact on the health of animals and humans is a significant public health risk all the time. Pb could be accumulated in the body for a long time, causing irreversible damage to the health of animals and humans, including hostile reproductive health. Up to now, although there are some published studies on impeding the normal development of ovarian folliculogenesis of female resulted from Pb exposure, with the damage of structure in uterine tissue, the imbalance of female menstrual status, and the change of hormone levels. The potential mechanism of Pb exposure on female reproduction system, however, remains enigmatic. How to alleviate the damage of Pb toxicity to reproductive function of female has become an urgent problem. Therefore, the aim of the present review is to discuss the information on the growth and development of ovarian follicle of mammalians and the potential toxic mechanism when exposed to Pb. The literatures were collected via various websites and consulting books, reports, etc. In summary, Pb impair folliculogenesis of mammalians, which may be related to the interference to the hypothalamic-pituitary-gonadal (HPG) axis and the production of reactive oxygen species (ROS), in turn impairs various molecules including proteins, lipids and DNA, as well as the disruption of the antioxidant defense system, ionic equilibrium and endoplasmic reticulum homeostasis.


Assuntos
Intoxicação por Chumbo/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Animais , Feminino , Humanos , Folículo Ovariano/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Reprodução/fisiologia
17.
Aquat Toxicol ; 236: 105861, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34049113

RESUMO

Man-made chemicals are a significant contributor to the ongoing deterioration of numerous ecosystems. Currently, risk assessment of these chemicals is based on observations in a single generation of animals, despite potential adverse intergenerational effects. Here, we investigate the effect of the fungicide prochloraz across three generations of Daphnia magna. We studied both the effects of continuous exposure over all generations and the effects of first-generation (F0) exposure on two subsequent generations. Effects at different levels of biological organization from genome-wide gene expression, whole organism metabolite levels, CYP enzyme activity and key phenotypic effects, such as reproduction, were monitored. Acclimation to prochloraz was found after continuous exposure. Following F0-exposure, embryonically exposed F1-offspring showed no significant effects. However, in the potentially germline exposed F2 animals, several parameters differed significantly from controls. A direct association between these F2 effects and the toxic mode of action of prochloraz was found, showing that chemicals can be harmful not only to the directly exposed generation, but also to prenatally exposed generations and in that way effects may even appear to skip a generation. This implies that current risk assessment practices are neglecting an important aspect of toxicity, such as delayed effects across generations due to a time gap between chemical exposure and emergence of effects.


Assuntos
Daphnia/fisiologia , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/efeitos dos fármacos , Ecossistema , Fungicidas Industriais/toxicidade , Avós , Reprodução/efeitos dos fármacos , Medição de Risco
18.
Aquat Toxicol ; 235: 105817, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33853019

RESUMO

Endocrine disrupting compounds (EDCs) are contaminants ubiquitously found in the environment, which pose a potential threat to aquatic and wetland ecosystems. Caiman latirostris, a crocodilian species that inhabits South American wetlands, is highly sensitive to EDC exposure. Previously, we reported that early postnatal exposure to EDCs such as Bisphenol A (BPA) and 17ß-Estradiol (E2) alters C. latirostris oviduct differentiation. The aim of this work was to elucidate the molecular mechanisms behind this alteration. To accomplish this, we established the ontogenic changes in histological features and the expression of Wnt-7a, Wnt-5a, ß-catenin, FoxA2, desmin, and alpha smooth muscle actin (α-SMA) in the oviduct of C. latirostris. Then, we evaluated the effects of BPA and E2 exposure on these histological features and protein expressions. Our results showed that during the postnatal differentiation of the oviduct the presence of histological features related to adenogenesis is associated with the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a. Early postnatal exposure to BPA and E2 decreased the presence of histological features related to adenogenesis and altered the levels of expression of FoxA2, ß-catenin, Wnt-5a and Wnt-7a, as well as the desmin/α-SMA ratio. These findings suggest that altered levels of Wnt-7a, Wnt-5a, ß-catenin and FoxA2 could play a role in the BPA and E2-induced alteration in oviduct differentiation in C. latirostris. Thus, impaired adenogenesis and, probably, impaired reproduction in wildlife naturally exposed to BPA and other estrogenic agonists cannot be completely ruled out.


Assuntos
Jacarés e Crocodilos/fisiologia , Estrogênios/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Compostos Benzidrílicos , Diferenciação Celular/efeitos dos fármacos , Ecossistema , Disruptores Endócrinos/toxicidade , Estradiol/farmacologia , Feminino , Hormônios Esteroides Gonadais , Humanos , Oviductos/efeitos dos fármacos , Fenóis , Reprodução/efeitos dos fármacos , beta Catenina
19.
Ecotoxicol Environ Saf ; 217: 112260, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33910068

RESUMO

The hypothesis that the inter-individual parameter variability is an unexploited area of ecotoxicology was proposed several decades ago. Although some illustrative examples were presented to support this hypothesis in the last decades, it has never been tested on an extensive, coherent database. In this study, variance changes of 105 dose-response curves were analysed. All data originated from the same experiment, where the effects of the insecticide Trebon EC were investigated in a dose-response manner on 15 traits of the collembolan Folsomia candida in four subsequent generations and two types of insecticide treatments. A consistent relationship between inter-individual variance and insecticide application was found in 2 (first clutch size and growth-reproduction trade-off) out of the 15 of the parameters. Contrary to the mean, the variance of the first clutch size showed consistent differences compared to the control. Furthermore, the variance of the growth-reproduction trade-off was consistently different from the control except in one case (F3 generation of the transgenerational treatment). Higher first clutch size variances were found in F1 and a lower one in the F2 and F3 generations than in that of the control. This overall pattern of the variance changes of the first clutch size and the trade-off seems to be a quick response to the insecticide application. In the short term, we have found that variance increased with insecticide treatment (P and F1 generation), because phenotypic variance generally increases due to environmental stress. Disruptive selection could be another mechanism between the more detoxification less reproduction strategy and the more reproduction less detoxification strategy. However, in the later generations (F2-F3) the variance decreases compared to the control, which could be because on short term selection stronger on the viability parameters and in long-term selection on reproduction becomes stronger. According to our results, analysis of the variance changes of some parameters may give information about the effects of the pesticide even when the mean does not predict any impact. Testing variance changes are important in ecotoxicology because variance change can signalise toxicant impact even when the mean does not change in certain cases.


Assuntos
Artrópodes/fisiologia , Inseticidas/toxicidade , Piretrinas/toxicidade , Animais , Tamanho da Ninhada , Fenótipo , Reprodução/efeitos dos fármacos
20.
Aquat Toxicol ; 235: 105838, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33910148

RESUMO

Dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) have been reported to exhibit reproductive toxicity in vertebrates. However, the combined effect of DBP and DiBP on offspring of exposed parents remains unclear, especially for aquatic organisms such as fish. The aims of this study were to assess the effects of parental co-exposure to DBP and DiBP on early development of zebrafish offspring, and to explore the potential molecular mechanisms involved. The early developmental indicators and transcriptomic profiles of F1 larvae were examined after parental exposure to DBP, DiBP and their mixtures (Mix) for 30 days. Results showed that parental exposure to DBP and DiBP, alone or in combination, resulted in increased hatchability at 48 hpf and heart rate at 96 hpf, and increased the prevalence of malformations and mortality in F1 larvae. Generalized linear model (GLM) suggested an antagonistic interactive effect between DBP and DiBP on mortality and malformations of F1 larvae. The transcriptomic analysis revealed that the molecular mechanisms of parental co-exposure were different from those of either chemical alone. Disruption of molecular functions involved unfolded protein binding, E-box binding and photoreceptor activity in F1 larvae. These findings provide initial insights in the potential mechanism of action of parental co-exposure to DBP and DiBP.


Assuntos
Dibutilftalato/análogos & derivados , Dibutilftalato/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Perfilação da Expressão Gênica , Reprodução/efeitos dos fármacos , Transcriptoma , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
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