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1.
Reprod Toxicol ; 128: 108662, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986849

RESUMEN

The Adverse Outcome Pathway (AOP) framework has gained widespread acceptance in toxicological disciplines as a tool for aiding chemical hazard assessment. Despite increased activity in AOP development, progress towards a high volume of fully endorsed AOPs has been slow, partly due to the challenging task of constructing complete AOPs according to the AOP Developer's Handbook. To facilitate greater uptake of new knowledge units onto the open-source AOP-wiki platform, a pragmatic approach was recently proposed. This approach involves considering Key Event Relationships (KERs) for individual development through systematic approaches, as they represent essential units of knowledge from which causality can be inferred; from low complexity test data to adverse outcomes in intact organisms. However, more broadly adopted harmonized methodologies for KER development would be desirable. Using the AOP Developer's Handbook as a guide, a KER linking 'decreased androgen receptor (AR) activity' with 'reduced anogenital distance (AGD)' was developed to demonstrate a methodology applicable for future developments of KERs requiring systematic literature retrieval approaches.


Asunto(s)
Rutas de Resultados Adversos , Receptores Androgénicos , Receptores Androgénicos/metabolismo , Humanos , Animales , Masculino , Femenino , Canal Anal/anatomía & histología , Canal Anal/efectos de los fármacos , Medición de Riesgo , Genitales/anatomía & histología , Genitales/efectos de los fármacos
2.
J Infect Dis ; 226(5): 907-919, 2022 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-35263421

RESUMEN

BACKGROUND: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). METHODS: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). RESULTS: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1ß, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. CONCLUSIONS: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. CLINICAL TRIALS REGISTRATION: NCT02550067.


Asunto(s)
Anticonceptivos Femeninos , Genitales , Femenino , Humanos , Anticoncepción/métodos , Anticonceptivos Femeninos/efectos adversos , Citocinas , Genitales/efectos de los fármacos , Genitales/patología , Infecciones por VIH/tratamiento farmacológico , Dispositivos Intrauterinos de Cobre/efectos adversos , Levonorgestrel/efectos adversos , Acetato de Medroxiprogesterona/efectos adversos
3.
Food Funct ; 13(5): 2631-2646, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35167640

RESUMEN

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.


Asunto(s)
Genitales/efectos de los fármacos , Ficocianina/farmacología , Sustancias Protectoras/farmacología , Animales , Línea Celular/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Animales , Ficocianina/química , Sustancias Protectoras/química , Espermatozoides/efectos de los fármacos
4.
Life Sci ; 295: 120404, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35176278

RESUMEN

AIMS: Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals. MATERIALS AND METHODS: Research records were screened from Embase, Medline, Scopus and Web of Science. Twelve original papers were identified and reviewed. Immunological, oxidative and morphofunctional outcomes, and the risk of bias in all studies reviewed were analyzed. KEY FINDINGS: These studies indicated that PP can accumulate in the gonads, triggering seminiferous degeneration, Sertoli cells death, blood-testis barrier disruption, sperm degeneration, malformation, reduced number and mobility, ovarian cysts, reduced follicular growth and granulosa cells death. Gonadal damage was associated with upregulation of prooxidant mediators (oxygen reactive species, lipid and DNA oxidation), cell death, proinflammatory molecular pathways and cytokines, as well as inhibition of enzymatic and non-enzymatic antioxidant defense mechanisms. Spermatogenesis, folliculogenesis, testosterone, progesterone and estrogen levels were also impaired in PP-treated animals, which were potentially associated with down-regulation of molecules involved in germ cells microstructural organization (occludin, N-cadherin, ß-catenin and connexin 43) and steroidogenesis, such as hydroxysteroid dehydrogenases, steroidogenic acute regulatory proteins, follicle stimulating and luteinizing hormones. Selection, performance and detection bias were the main limitations identified. SIGNIFICANCE: Current evidence indicates that PP can induce dose-dependent microstructural and functional gonadal damage, which is orchestrated by pro-oxidant and pro-inflammatory mechanisms that disrupt genes, molecular effectors, and hormones that control spermatogenesis and folliculogenesis.


Asunto(s)
Genitales/efectos de los fármacos , Microplásticos/efectos adversos , Reproducción/efectos de los fármacos , Animales , Estrógenos , Femenino , Células Germinativas/efectos de los fármacos , Células de la Granulosa/metabolismo , Inflamación , Mucosa Intestinal/efectos de los fármacos , Hormona Luteinizante , Masculino , Mamíferos/metabolismo , Mamíferos/fisiología , Folículo Ovárico/metabolismo , Ovario , Estrés Oxidativo , Plásticos/efectos adversos , Progesterona , Células de Sertoli/metabolismo , Espermatogénesis , Testículo , Testosterona
6.
Braz. J. Pharm. Sci. (Online) ; 58: e19264, 2022. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1374563

RESUMEN

Abstract This study investigates the toxic effects of ethanol (Eth) on the reproductive system of male rats and the possible protective role of Silybum marianum seeds-infused solution (SMI) over six consecutive weeks of administration. Animals were divided into the following groups: control, SMI positive control (200 mg/kg/day), Eth1 (1 g/kg/day), Eth2 (2 g/kg/day), Eth1+SMI, and Eth2+SMI. Plasma testosterone concentration, epididymal spermatozoa biology, and testicular and epididymal MDA, GSH and GPx levels were evaluated. The results indicated a significant decrease in testis and epididymis weight, testosterone level, sperm concentration, sperm vitality and sperm motility (total motility, progressive motility, curvilinear velocity, straight-line velocity, velocity average path, beat cross frequency, and lateral head displacement) in both Eth1 and Eth2 compared to the control groups and the combined-treatment groups (Eth1+SMI and Eth2+SMI). Furthermore, results showed a significant elevation in MDA concentration with a significant decrease of testicular and epididymal GSH concentration and GPx activity in theEth1 and Eth2 groups compared to the combined-treatment groups. The administration of SMI succeeded in improving the parameters cited above in the combined-treatment groups compared to the Eth1 and Eth2 groups, and bring them to the levels seen in the control groups. To conclude, SMI has clearly protected reproductive indices against ethanol-induced reprotoxicity in male rats


Asunto(s)
Animales , Masculino , Ratas , Silybum marianum/anatomía & histología , Etanol/efectos adversos , Semillas/efectos adversos , Espermatozoides/clasificación , Testículo , Toxicidad , Genitales/efectos de los fármacos
7.
Eur Rev Med Pharmacol Sci ; 25(15): 4930-4940, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34355365

RESUMEN

OBJECTIVE: Chemicals that disrupt the endocrine homeostasis of the human body, otherwise known as endocrine disruptors (EDCs), are found in the blood, urine, amniotic fluid, or adipose tissue. This paper presents the current knowledge about EDCs and the reproductive system. MATERIALS AND METHODS: The article is an overview of the impact of EDCs and their mechanism of action, with particular emphasis on gonads, based on the information available on medical databases (PubMed, Web of Science, EMBASE and Google Scholar, EMBASE and Web of Science) until May 2021. RESULTS: EDCs occur in everyday life, e.g., they are components of adhesives, brake fluids, and flame retardants; they are used in the production of polyvinyl chloride (PVC), plastic food boxes, pacifiers, medicines, cosmetics (bisphenol A, phthalates), hydraulic fluids, printing inks (polychlorinated biphenyls - PCBs), receipts (bisphenol A, BSA) and raincoats (phthalates); they are also a component of polyvinyl products (e.g. toys) (phthalates), air fresheners and cleaning agents (phthalates); moreover, they can be found in the smoke from burning wood (dioxins), and in soil or plants (pesticides). EDCs are part of our diet and can be found in vegetables, fruits, green tea, chocolate and red wine (phytoestrogens). In addition to infertility, they can lead to premature puberty and even cause uterine and ovarian cancer. However, in men, they reduce testosterone levels, reduce the quality of sperm, and cause benign testicular tumors. CONCLUSIONS: Therefore, this article submits that EDCs negatively affect our health, disrupting the functioning of the endocrine system, and particularly affecting the functioning of the gonads.


Asunto(s)
Disruptores Endocrinos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/efectos adversos , Genitales/efectos de los fármacos , Femenino , Humanos , Masculino
8.
Reprod Toxicol ; 105: 17-24, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34380069

RESUMEN

Synthetic amorphous silica (SAS) consists of agglomerates and aggregates of primary particles in the nanorange (<100 nm) and it is the E551 authorized food additive. The potential risks for human health associated to dietary exposure to SAS are not completely assessed; in particular, data on male and female reproductive systems are lacking. A 90-day oral toxicity study with pyrogenic SAS nanomaterial NM-203 was carried out on the basis of the OECD test guideline 408 in the frame of the NANoREG project. Adult Sprague-Dawley rats of both sexes were orally treated for 90 days with 0, 2, 5, 10, 20 and 50 mg SAS/kg bw per day. Dose levels were selected to be as close as possible to the expected human exposure to food additive E551. The present paper provides specific information on potential effects on male and female reproductive systems, through the evaluation of serum biomarkers, sperm count, histopathological analysis of testis, epididymis, ovary and uterus and real-time PCR on uterus; potential genotoxic alterations were evaluated by comet assay on testis, sperm and ovary. NM-203 did not induce histophatological and genotoxic effects in male reproductive system. In female rats, ovary is not target of NM-203 and only tissue-specific effects on uterus were recorded up to 10 mg/kg bw per day. To our best knowledge, this is the first study providing data on male and female reproductive systems after long-term, repeated oral exposure at dose levels close to dietary human exposure, which identifies a limited concern only for female reproductive health.


Asunto(s)
Dióxido de Silicio/toxicidad , Administración Oral , Animales , Ensayo Cometa , Estradiol/sangre , Femenino , Expresión Génica/efectos de los fármacos , Genitales/efectos de los fármacos , Genitales/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Ratas Sprague-Dawley , Recuento de Espermatozoides , Testosterona/sangre , Pruebas de Toxicidad Subcrónica
9.
Basic Clin Pharmacol Toxicol ; 129(3): 183-195, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34196104

RESUMEN

The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 µM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.


Asunto(s)
Epidídimo/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Animales , Aspirina , Dipirona , Epidídimo/fisiología , Genitales/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Recuento de Espermatozoides , Testosterona/sangre , Testosterona/metabolismo
10.
Front Immunol ; 12: 660932, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936096

RESUMEN

Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Infecciones por Chlamydia/prevención & control , Chlamydia muridarum/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Genitales/efectos de los fármacos , Nanopartículas/química , Adyuvantes Inmunológicos , Animales , Anticuerpos Antibacterianos/sangre , Péptidos Catiónicos Antimicrobianos/administración & dosificación , Péptidos Catiónicos Antimicrobianos/química , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/genética , Vacunas Bacterianas/administración & dosificación , Citocinas/inmunología , Femenino , Genitales/microbiología , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Vacunación
11.
Regul Toxicol Pharmacol ; 122: 104914, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33684452

RESUMEN

Ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate, used in laundry detergents, shampoos, and body soaps, is classified by the Japanese Chemical Substances Control Law as a priority assessment chemical substance for environmental effects. However, its toxicity data for human health are insufficient. This study evaluated this chemical under the Safety Examination of Existing Chemicals and Safety Programmes of the Ministry of Health, Labour and Welfare (MHLW). The MHLW conducted bacterial reverse mutation (Ames test), in vitro chromosomal aberration, and combined repeated-dose and reproductive/developmental toxicity screening tests. We performed a screening assessment of ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate for human health. The chemical showed a negative reaction in the Ames test and a positive reaction in the in vitro chromosomal aberration test with metabolic activation in rats. The combined repeated-dose and reproductive/developmental toxicity screening test showed significantly decreased food consumption at 50 mg/kg body weight/day, but no reproductive and developmental toxicity was observed. The no-observed-effect level of 15 mg/kg/day was obtained as a screening value. Therefore, this chemical was classified as hazard class 3, with a derived-no-effect level of 0.025 mg/kg/day. The results of this study will be useful for risk assessment of groups of structurally similar alkyl quaternary ammonium surfactants.


Asunto(s)
Genitales/efectos de los fármacos , Compuestos de Amonio Cuaternario/toxicidad , Animales , Línea Celular , Cricetinae , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos , Femenino , Masculino , Pruebas de Mutagenicidad , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
12.
Artículo en Inglés | MEDLINE | ID: mdl-33753303

RESUMEN

Vitellogenin has been regarded as an acceptable indicator for evaluating the endocrine-disrupting property of chemicals using fish. However, the endocrine-disrupting property of chemicals has been rarely evaluated using soil species. This study aimed to find evidence that endocrine-disrupting chemicals (including the natural hormones estradiol and dihydrotestosterone) can affect the reproductive organs of earthworms. Earthworms were exposed to 17ß-estradiol, dihydrotestosterone, bisphenol A, and methylparaben for seven days. The four EDCs inhibited normal oogenesis and maturation of oocytes in earthworm ovary, and dihydrotestosterone and bisphenol A were observed to damage earthworm seminal vesicle tissues and inhibit normal spermatogenesis. The evidence showed that the tested EDCs have an adverse effect on female and male reproductive systems of soil invertebrates. The results suggest that the evaluations of oogenesis and spermatogenesis in the ovary and seminal vesicles of earthworms are useful indicators for investigating the endocrine-disrupting property of chemicals. Additionally, our results encourage further studies on developing novel indicators using soil invertebrates to evaluate the effects of the toxicity of endocrine-disrupting chemicals on the soil ecosystem.


Asunto(s)
Disruptores Endocrinos/toxicidad , Genitales/efectos de los fármacos , Oligoquetos/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Animales , Compuestos de Bencidrilo/toxicidad , Dihidrotestosterona/toxicidad , Estradiol/toxicidad , Femenino , Masculino , Parabenos/toxicidad , Fenoles/toxicidad
13.
Regul Toxicol Pharmacol ; 122: 104897, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33639256

RESUMEN

Benzoic acid (BA) was administered in the diet to male and female Sprague Dawley Crl:CD(SD) rats in an OECD Test Guideline 443 Extended One-Generation Reproductive Toxicity (EOGRT) study to test for effects that may occur as a result of pre- and postnatal exposure. The study included cohorts of F1 offspring to evaluate potential effects of benzoic acid on reproduction, the developing immune system, and the developing neurological system with the inclusion of learning and memory assessments. Benzoic acid was incorporated in the diet at concentrations of 0, 7,500, 11,500, and 15,000 mg/kg diet (ppm). These concentrations were selected based on the results of preliminary studies, and, based on average food consumption, were intended to supply BA doses of approximately 0, 500, 750, and 1000 mg/kg bw/day. To avoid exceeding these target dose levels, the dietary concentrations were adjusted (based on historical control body weight and food consumption data) to maintain the target mg/kg bw/day dose levels during those life periods when food intake per unit of body weight was increased to support milk production by females (gestation and lactation) and rapid pup growth (post-weaning). In the parental (F0) generation, survival, clinical observations, organ weights, pathology, hematology, serum chemistry, urinalysis, and bile acids were unaffected by BA administration. Reproductive parameters were also unaffected by BA administration. In the F1 generation, survival, growth and developmental landmarks, organ weights, pathology, immunotoxicity assessment, and neurotoxicity and neurobehavioral parameters such as auditory startle response, locomotor activity, learning and memory assessments were unaffected by BA administration, as were clinical pathology (hematology, serum chemistry, urinalysis, bile acids and thyroid hormones) and reproductive performance. Similarly, no adverse effects or systemic toxicity were observed in the F2 generation. Overall, the highest dietary concentration (15,000 ppm), providing a dosage of approximately 1000 mg/kg bw/day, was the NOAEL for benzoic acid in this EOGRT study.


Asunto(s)
Ácido Benzoico/farmacología , Conservantes de Alimentos/farmacología , Genitales/efectos de los fármacos , Animales , Peso Corporal , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
14.
Artículo en Inglés | MEDLINE | ID: mdl-33610819

RESUMEN

Endocrine disruptors (EDs) interfere with different hormonal and metabolic processes and disrupt the development of organs and tissues, as well as the reproductive system. In toxicology research, various animal models have been utilized to compare and characterize the effects of EDs. We reviewed studies assessing the effect of ED exposure in humans, zebrafish, and mouse models and the adverse effects of EDs on male and female reproductive systems. This review outlines the distinctive morphological characteristics, as well as gene expression, factors, and mechanisms that are known to occur in response to EDs. In each animal model, disturbances in the reproductive system were associated with certain factors of apoptosis, the hypothalamic-pituitary-gonadal axis, estrogen receptor pathway-induced meiotic disruption, and steroidogenesis. The effects of bisphenol A, phthalate, and 17α-ethinylestradiol have been investigated in animal models, each providing supporting outcomes and elaborating the key regulators of male and female reproductive systems.


Asunto(s)
Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Etinilestradiol/toxicidad , Genitales/efectos de los fármacos , Fenoles/toxicidad , Ácidos Ftálicos/toxicidad , Animales , Femenino , Humanos , Masculino , Ratones , Pez Cebra
15.
Reprod Toxicol ; 100: 126-136, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33513405

RESUMEN

Benzo(a)pyrene (BaP) is an ubiquitous environmental pollutant which can lead to adverse effects on male reproduction. However, the persistence of these changes on a multigenerational scale has not been sufficiently explored. This study evaluated if peripubertal exposure to BaP in male rats can induce reproductive impairment in offspring. Male rats received BaP at environmentally relevant doses (0, 0.1, 1, or 10 µg/kg/day) orally from post-natal (PND) 23-53. On PND 90, treated males were mated with non-treated females for obtaining the next generation (F1). The paternal exposure to BaP decreased the body weight of offspring on PND 1, 13 and 22, as well as it provoked a reduction in the relative anogenital distance of the males. This exposure also brought forward the onset of puberty, evidenced by an earlier vaginal opening and first estrous in females of the lowest dose group and by a delay in the testicular descent and preputial separation ages in males. The males presented a decrease in the daily sperm production and a disrupted sperm morphology. Furthermore, the testicular histology was altered, evidenced by a reduction in the Leydig cell numbers and in the seminiferous tubules diameter, as well as a disrupted seminiferous tubules staging. The estrous cyclicity and some fertility parameters were changed in the females, as well as alterations in the ovary and uterus histology were observed. BaP compromised several reproductive parameters of the F1 generation, suggesting that peripubertal exposure to this compound provokes permanent modifications in male germ line of F0 generation.


Asunto(s)
Benzo(a)pireno/toxicidad , Contaminantes Ambientales/toxicidad , Exposición Paterna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Reproducción/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Animales , Benzo(a)pireno/administración & dosificación , Peso Corporal/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Genitales/efectos de los fármacos , Genitales/crecimiento & desarrollo , Masculino , Tamaño de los Órganos , Embarazo , Ratas , Ratas Wistar , Espermatozoides/efectos de los fármacos
16.
Ann Pharmacother ; 55(4): 543-548, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32808541

RESUMEN

OBJECTIVE: To review the incidence, risk factors, prevention, and management of genital mycotic infections (GMIs) associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. DATA SOURCES: A literature search of PubMed and Reactions Weekly was performed in February 2020 with updated searches monthly through July 2020 to identify relevant data regarding SGLT2 inhibitors and GMIs. Manufacturers of each agent were contacted, and clinical practice guidelines were consulted. STUDY SELECTION AND DATA EXTRACTION: All available literature was evaluated for inclusion based on relevance to the research question, timeliness of the publication, validity, and impact on current practice. A date limit was not set; however, publications from 2010 to July 2020 were prioritized. DATA SYNTHESIS: The 3- to 4-fold increased incidence of GMIs is considered a classwide effect of SGLT2 inhibitors. Female sex and a prior history of GMIs are factors associated with the highest risk, whereas circumcised males are at the lowest risk of SGLT2 inhibitor-induced GMI. Personal hygiene advice can reduce the infection risk. When candidiasis occurs, it is often mild and responsive to treatment and often does not require discontinuation of the medication. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This narrative review can assist in shared decision-making discussions with patients who may benefit from SGLT2 inhibitors and provides guidance for health care professionals managing SGLT2 inhibitor-associated GMIs. CONCLUSIONS: SGLT2 inhibitors predispose patients to developing mild GMIs. Strong consideration should be given to avoid SGLT2 inhibitors in female patients with a history of severe, recurrent infections. Preventive strategies are optimized diabetes management and personal hygiene advice.


Asunto(s)
Candidiasis Vulvovaginal/inducido químicamente , Candidiasis Vulvovaginal/prevención & control , Manejo de la Enfermedad , Genitales/efectos de los fármacos , Higiene , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Canagliflozina/efectos adversos , Canagliflozina/uso terapéutico , Candidiasis Vulvovaginal/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Genitales/microbiología , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Masculino , Transportador 2 de Sodio-Glucosa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
17.
Regul Toxicol Pharmacol ; 120: 104840, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33321148

RESUMEN

In 2017, JECFA requested reproductive and developmental toxicity studies to finalize an acceptable daily intake for solvent rosemary extracts. Thus, an OECD 421 reproductive/developmental toxicity study was conducted using an acetone rosemary extract that complied with JECFA and EFSA food additive specifications. Rosemary extract was provided to rats at dietary concentrations of 0 (control), 2100, 3600, or 5000 mg/kg, for 14 days before mating, during mating, and thereafter (throughout gestation and up to Lactation Day 13 for females) until necropsy. General toxicity (clinical signs, body weight, food consumption) and reproductive/developmental outcomes (fertility and mating performance, estrous cycles, anogenital distance, thyroid hormones, reproductive organ weights, thyroid histopathology) were assessed. There were no signs of general toxicity and no effects on reproduction; thus, the highest concentration tested (equivalent to mean daily intakes of 316 or 401 mg/kg bw/day [149 or 189 mg/kg bw/day carnosol and carnosic acid] for males and females, respectively) was established as the no-observed-adverse-effect level for general and reproductive toxicity. Dose-related reductions in T4 were observed for Day 13 pups (not seen on Day 4) but were not accompanied by thyroid weight changes or histopathological findings; further investigations are required to determine the biological relevance of these T4 reductions.


Asunto(s)
Acetona/toxicidad , Genitales/efectos de los fármacos , Extractos Vegetales/toxicidad , Reproducción/efectos de los fármacos , Rosmarinus , Animales , Animales Recién Nacidos , Discapacidades del Desarrollo/inducido químicamente , Discapacidades del Desarrollo/patología , Evaluación Preclínica de Medicamentos/métodos , Femenino , Genitales/fisiología , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos , Extractos Vegetales/aislamiento & purificación , Embarazo , Ratas , Reproducción/fisiología
18.
Artículo en Inglés | MEDLINE | ID: mdl-33382011

RESUMEN

Arsenic contamination in the groundwater of Southern Assam, India is well-documented. A specific type of smokeless tobacco (sadagura, SG) is highly prevalent among the local population. Thus, the present study is aimed to evaluate the toxicological implications of arsenic and smokeless tobacco co-exposure on the reproductive health of female mice. The estrous cycle of experimental animals was monitored for 30 days. Histopathological studies and comet assay of ovarian and uterine tissues were performed after 30 days of exposure to SG and arsenic (sodium arsenite, SA). Oxidative stress was estimated biochemically by taking tissue glutathione, lipid peroxidation (LPO), and superoxide dismutase activity as endpoints. Our findings indicated a prolonged diestrus phase in the SG + L + SA group (p < 0.001). Histopathological study revealed abnormal tissue architecture in treated groups. Comet assay study showed that SG + SA exposure significantly induced DNA damage in test animals. The elevated LPO level in the SG + SA group indicated oxidative stress generation in the reproductive tissues. The present study suggests that female reproductive organs are vulnerable to SA and SG and oxidative stress generation may be the possible mechanism behind DNA damage, impaired follicular growth, atresia, and altered estrous cycle in the mice test system.


Asunto(s)
Arsénico/toxicidad , Genitales/efectos de los fármacos , Tabaco sin Humo/toxicidad , Animales , Antioxidantes/metabolismo , Daño del ADN , Femenino , Genitales/fisiología , Glutatión/metabolismo , Peroxidación de Lípido , Ratones , Estrés Oxidativo
19.
Chin J Physiol ; 63(5): 235-243, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33109790

RESUMEN

Although selenium is known to be essential for reproductive function, studies have indicated the adverse effect with its prolonged use. The present study investigated the duration-related effect of selenium administrations on reproductive hormones and estrous cycle indices in adult female Wistar rats exposed to a model of light pollution using altered photoperiod (AP). Ninety-six cyclic female Wistar rats displaying 4-5 days' estrous cycle length (ECL) and weighing 148-152 g were randomly divided into short and long experimental cohorts consisting of six groups each and spanning for 1 and 8 weeks, respectively. Each consisted of control, high selenium dose (HSE), low selenium dose (LSE), AP, AP + HSE, and AP + LSE. The rats were orally administered high dose (150 µg/kg) and low dose (100 µg/kg) of sodium selenite once per day. The estrous cycle indices were monitored. Plasma levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E), progesterone (P), prolactin, E/P ratio, and histology of ovary and uterine horn were evaluated. The statistical analysis was performed using Statistical Package for the Social Sciences. In AP rats, HSE and LSE caused no significant effect on LH, E, P, and E/P ratio, ECL, estrus interval (EI), and estrous cycle ratio (ECR). The effect of HSE and LSE on LH, E, P, E/P ratio, and ECL showed no duration-dependent increase, but there was a duration-dependent increase in EI and ECR at low dose. The study indicated that administration of HSE of selenium improved reproductive function in photo-pollution-exposed rats irrespective of the duration of treatment.


Asunto(s)
Genitales/efectos de los fármacos , Genitales/efectos de la radiación , Homeostasis/efectos de los fármacos , Fotoperiodo , Selenio/administración & dosificación , Animales , Estradiol , Femenino , Hormona Folículo Estimulante , Genitales/fisiopatología , Hormona Luteinizante , Ratas , Ratas Wistar
20.
J Insect Physiol ; 126: 104094, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32783957

RESUMEN

Methoprene supplements added to diets of yeast hydrolysate and sugar promote early expression of sexual behaviour and mating in male Queensland fruit fly (Bactrocera tryoni; 'Q-fly') and show promise as a pre-release treatment for sterile insect technique programs. Currently it is not known whether the early mating behaviour of methoprene-treated male Q-flies is only behavioural or is coupled with accelerated development of reproductive organs. Accordingly, the present study investigates whether incorporation of methoprene into diets of yeast hydrolysate and sugar (1:3) or sugar alone, accelerate development of testes, ejaculatory apodeme, and accessory glands in male Q-flies and ovaries in females. All organs increased in size as the flies aged and matured, and development rate of all organs was far greater when the flies were provided yeast hydrolysate in addition to sugar. Incorporation of methoprene into diets containing yeast hydrolysate was found to strongly accelerate development of testes and ejaculatory apodeme, but not accessory glands, in males. In the absence of yeast hydrolysate, methoprene treatment had only a modest effect on male organ development. In contrast to males, development of ovaries in female Q-flies did not respond to dietary methoprene supplements, regardless of whether they were fed yeast hydrolysate and sugar or sugar alone. These findings of diet-dependent effects of methoprene supplements on reproductive organs are a close match to previous studies investigating effects of methoprene supplements on mating behaviour. Overall, methoprene supplements substantially enhance the positive effects of protein rich adult diet on the early expression of sexual behaviour and accelerate development of reproductive organs in male, but not female, Q-flies. Methoprene supplements added to pre-release diets of yeast hydrolysate and sugar show promise as a means of accelerating reproductive development of Q-flies released in sterile insect technique programs, and may also bias operational sex ratio in favour of males.


Asunto(s)
Genitales/efectos de los fármacos , Metopreno/farmacología , Tephritidae/crecimiento & desarrollo , Animales , Dieta , Suplementos Dietéticos , Femenino , Control de Insectos/métodos , Masculino , Ovario/efectos de los fármacos , Control Biológico de Vectores/métodos , Saccharomyces cerevisiae , Razón de Masculinidad , Testículo/efectos de los fármacos
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