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1.
Ann Hematol ; 100(11): 2831-2841, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34536088

RESUMO

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.


Assuntos
Aconselhamento/métodos , Preservação da Fertilidade/métodos , Adolescente , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Criopreservação , Feminino , Preservação da Fertilidade/economia , Preservação da Fertilidade/normas , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/etiologia , Infertilidade Feminina/prevenção & controle , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/etiologia , Infertilidade Masculina/prevenção & controle , Masculino , Neoplasias/terapia , Recuperação de Oócitos , Ovário/transplante , Estudos Prospectivos , Puberdade , Lesões por Radiação/prevenção & controle , Radioterapia/efeitos adversos , Preservação do Sêmen , Condicionamento Pré-Transplante/efeitos adversos , Adulto Jovem
2.
J Assist Reprod Genet ; 38(11): 3057-3060, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34472016

RESUMO

PURPOSE: Fertility preservation is a critical patient counseling component following cancer diagnosis. The aim of this study was to compare change and quality of fertility preservation information available to patients on the websites of National Cancer Institute (NCI)-designated cancer centers over 5 years (2015 to 2020) for both women and men. METHODS: All NCI-designated cancer center websites were queried for information on oncofertility in 2020 publicly available to patients using the methodology and rubric previously employed in 2015. Data was evaluated based on each center's city, county, and state by demographic data obtained from the US Census. Additionally, the yearly number of in vitro fertilization (IVF) cycles performed in the city, county, and state of each NCICC was included using websites of clinics reporting data to the Society for Assisted Reproductive Technology. RESULTS: Significantly NCICCs have a standalone pages for fertility preservation in 2020 compared with 2015 (p = 0.004). There is a statistically significant association between discussion of male fertility and the number of fertility centers in the county and state of the NCICC (p = 0.04 and p = 0.001). NCICCs in counties in the highest quartile of per capita income were significantly more likely to address male fertility (p = 0.03). CONCLUSIONS: Oncofertility information on NCICC websites has improved between 2015 and 2020. The impact of cancer treatment on male fertility, while improved, is still limited, particularly in counties with lower per capita income.


Assuntos
Antineoplásicos/efeitos adversos , Preservação da Fertilidade , Infertilidade Masculina/terapia , Internet/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Medição de Risco/métodos , Adulto , Fertilização in vitro/métodos , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , National Cancer Institute (U.S.) , Neoplasias/fisiopatologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo , Estados Unidos
3.
BMC Public Health ; 20(1): 64, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941472

RESUMO

BACKGROUND: Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion. METHODS: We performed an online survey investigating consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life. RESULTS: Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic. CONCLUSIONS: The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.


Assuntos
Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Peixes , Contaminação de Alimentos/análise , Alimentos Marinhos/análise , Adulto , Animais , Criança , Dioxinas/efeitos adversos , Dioxinas/análise , Estudos de Avaliação como Assunto , Feminino , Humanos , Recém-Nascido , Infertilidade Masculina/induzido quimicamente , Masculino , Compostos de Metilmercúrio/efeitos adversos , Compostos de Metilmercúrio/análise , Valor Nutritivo , Gravidez , Medição de Risco , Salmão , Países Escandinavos e Nórdicos , Doenças Dentárias/induzido quimicamente
4.
Sci Total Environ ; 662: 615-621, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30699382

RESUMO

While it has been acknowledged that exposure to endocrine-disrupting chemicals (EDCs) is associated with human diseases, the overall disease burden attributable to the exposure to a specific EDC has rarely been evaluated. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we analyzed the burden of three diseases, i.e., male infertility, adult obesity, and diabetes, among the general Chinese population resulting from exposure to phthalates. Our estimation indicates that exposure to phthalates is associated with ~2.50 million cases of the three diseases across China in 2010, causing ~57.2 billion Chinese Yuan (equivalent to ~9 billion US dollars) of health care costs in a year. Male infertility has the largest number of cases, followed by adult obesity and diabetes. Based on these phthalate-specific estimates, we further estimated that the total disease cost due to exposure to the overall EDCs amounted to ~429.43 billion Chinese Yuan in China in 2010, accounting for 1.07% of nationwide gross domestic product (GDP). When comparing our results with an earlier estimate for the European Union (EU) member countries, we find that exposure to phthalates leads to quite a similar disease burden per unit of GDP in both regions. Our study illustrates the considerable socio-economic impact of EDC exposure on human society, implying the imperative need for global risk reduction actions on EDCs, especially in view of the 2030 Sustainable Development Goals.


Assuntos
Diabetes Mellitus/economia , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Infertilidade Masculina/economia , Obesidade/economia , Ácidos Ftálicos/efeitos adversos , China , Efeitos Psicossociais da Doença , Diabetes Mellitus/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Obesidade/induzido quimicamente
5.
Toxicol In Vitro ; 48: 93-103, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29307701

RESUMO

Epidemiological studies show that there is global decline in male fertility primarily as a result of poor sperm quality and this is attributed to exposure to endocrine disrupting chemicals (EDCs) in the environment, food and pharmaceutical products, including mycotoxins and pesticides. The Leydig cells in the male testes are responsible for producing androgens, hormones that play major roles in male development and reproductive function. Therefore, any toxin that affects the function and morphology of the Leydig cells may result in sub-fertility or infertility. The cytotoxic effects of single and binary mixtures of aflatoxin B1 (AFB1), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), alpha-zearalenol (α-ZOL), beta-zearalenol (ß-ZOL), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) on a model cell line, the MA-10 Leydig cells, were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-dipenyltetrazolium bromide (MTT) assay after 48h of exposure. With single toxin treatment at doses between 0.1µM and 64µM for 48h, DON was the most cytotoxic to MA-10 cells with a half maximal inhibitory concentration (IC50) value of 12.3µM followed by α-ZOL (IC50: 28µM) and OTA (IC50: 30µM) while the IC50 of AFB1, p,p'-DDT and p,p'-DDE were above the highest concentration tested (64µM). Co-exposure with p,p'-DDT or p,p'-DDE enhanced the toxicity of DON, OTA and ZEN to MA-10 Leydig cells, particularly at higher concentrations. This highlights the possible adverse effects on male reproductive health following co-exposure to these toxins.


Assuntos
Hidrocarbonetos Clorados/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Micotoxinas/toxicidade , Praguicidas/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/patologia , Masculino , Camundongos , Resíduos de Praguicidas/toxicidade
6.
Andrologia ; 50(3)2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29047156

RESUMO

Effects of Lepidium meyenii (Maca) on cyclophosphamide (CYP)-induced gonadal toxicity in male mice were investigated. Mice were assigned to six treatment groups: Vehicle control, CYP control, CYP plus oral Maca (500 or 1,000 mg/kg), and oral Maca (500 or 1,000 mg/kg). CYP was administered via the intraperitoneal route (days 1-2), while vehicle or Maca were administered daily for 28 days. On day 28, half of the animals in each group were either sacrificed or paired with age-matched females for fertility assessment. Plasma testosterone assay, sperm analysis and assessment of tissue antioxidant/morphological status were also carried out. CYP administration was associated with oxidative stress, subfertility and morphometric/morphological indices of gonadal injury, while administration of Maca mitigated CYP-induced gonadal toxicity and subfertility. This study shows that Maca is beneficial in the mitigation of CYP-induced male gonadal insufficiency and/or testicular morphological changes; however, further studies will be needed to ascertain its usability for this purpose in humans.


Assuntos
Ciclofosfamida/efeitos adversos , Infertilidade Masculina/tratamento farmacológico , Lepidium , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Espermatozoides/efeitos dos fármacos , Testosterona/sangue , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Infertilidade Masculina/induzido quimicamente , Masculino , Camundongos , Extratos Vegetais/farmacologia , Análise do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos
7.
Drug Chem Toxicol ; 40(2): 171-182, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27308970

RESUMO

CONTEXT: Diplazium esculentum, a commonly consumed seasonal vegetable, has been reported to have some pathological effects in some animals. But, its effect on the male reproductive function has not yet been studied. OBJECTIVE: To investigate the effects of boiled D. esculentum (BDE), the form which human consumes, on male reproductive functions of Swiss albino mice. MATERIALS AND METHODS: Male (120 in no.) and female (80 in no.) Swiss albino mice (6-8 weeks of age) were fed orally with 80, 160 and 320 mg/kg bw of BDE within a span of 180 d. After the treatment, body weight, absolute- and relative-testis weight, relative-weight of other organs, their biochemical parameters, hypo-osmotic swelling test (HOST) of spermatozoa, testis histology and fertility and fecundity tests were performed to justify the toxic effects of D. esculentum on male reproductive functions. RESULTS: Significant dose- and time-dependent decreases were observed in body weight, absolute- and relative-testis weight, relative-weights of other organs and their biochemical parameters, percentage of live spermatozoa and percentage of fertility and fecundity in BDE fed mice. Significant decreases were observed in diameter, perimeter and area of the seminiferous tubules of mice treated for 180 d. The percentage of empty seminiferous tubules was increased significantly in BDE treated mice when compared to the controls. DISCUSSION AND CONCLUSION: These results suggest that the intake of D. esculentum, even after cooking, may induce infertility by altering the male reproductive function, and therefore, should be evaluated further as a potential antifertility agent.


Assuntos
Gleiquênias/toxicidade , Infertilidade Masculina/induzido quimicamente , Extratos Vegetais/toxicidade , Reprodução/efeitos dos fármacos , Túbulos Seminíferos/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos , Tamanho do Órgão , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Gravidez , Medição de Risco , Túbulos Seminíferos/patologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia , Testículo/fisiopatologia , Fatores de Tempo , Testes de Toxicidade , Redução de Peso/efeitos dos fármacos
8.
J Clin Endocrinol Metab ; 100(4): 1267-77, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25742517

RESUMO

INTRODUCTION: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. PURPOSE: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). METHODS: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. RESULTS: The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. CONCLUSIONS: EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.


Assuntos
Efeitos Psicossociais da Doença , Disruptores Endócrinos/toxicidade , União Europeia/economia , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/economia , Adulto , Mudança Climática , Criptorquidismo/induzido quimicamente , Criptorquidismo/economia , Criptorquidismo/epidemiologia , Exposição Ambiental/economia , Exposição Ambiental/estatística & dados numéricos , Eunuquismo/induzido quimicamente , Eunuquismo/economia , Eunuquismo/epidemiologia , União Europeia/estatística & dados numéricos , Humanos , Infertilidade Masculina/epidemiologia , Masculino , Neoplasias Embrionárias de Células Germinativas/induzido quimicamente , Neoplasias Embrionárias de Células Germinativas/economia , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Testiculares/induzido quimicamente , Neoplasias Testiculares/economia , Neoplasias Testiculares/epidemiologia , Poluentes Químicos da Água/toxicidade
9.
J Ethnopharmacol ; 174: 582-94, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-25818692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea asarifolia (Convolvulacae), commonly known as "morning glory" is found across West Africa. Preparations of the plant are used traditionally for the treatment of diverse ailments including diabetes, neuralgia, arthritic pain and stomach ache. This study was designed to assess the safety profile of the hydroethanolic leaf extract of I. asarifolia through a 90-day subchronic toxicity study in rats. MATERIALS AND METHODS: I. asarifolia was administered p.o. at doses of 40, 200 and 1000mg/kg to separate groups of rats for 90 days. Distilled water was given p.o. to rats in the control group. Some set of rats in each group were left for additional 30 days without administration of the extract for reversibility study. Animals were weighed weekly and relevant parameters were assayed at the end of the main and reversibility study periods. RESULTS: There was no significant change (p>0.05) in the body weight of rats, and food and water intake in I. asarifolia treated groups compared with control. I. asarifolia (40-1000 mg/kg) significantly but reversibly reduced (p<0.05, 0.001) sperm motility and count. The extract did not generally cause significant change (p>0.05) in the weight of vital organs and haematological parameters except in the case of reversible reduction in the level of haemoglobin and red blood cell count (p<0.01; 40 mg/kg). The level of biochemical parameters and electrolytes were not significantly changed (p>0.05) except for the reversible reduction in the level of aspartate aminotransferase (AST; p<0.0001; 200 and 1000 mg/kg) and increase in the level of Na(+) (p<0.01; 200 mg/kg). The level of kidney reduced glutathione (GSH) was reversibly increased (p<0.01; 1000 mg/kg) while the level of enzymatic and non-enzymatic in vivo antioxidants was generally comparable and not significantly different (p>0.05) from control in respect of all other vital organs. Histological presentations were generally normal in respect of the liver, kidneys, brain, heart, lungs, pancreas, spleen and testes. CONCLUSIONS: The findings in this study suggest that the hydroethanolic leaf extract of I. asarifolia is relatively safe administered orally for an extended period with potential renal in vivo antioxidant activities. However, the extract may cause reversible male sterility, anaemia and hypernatraemia.


Assuntos
Ipomoea/química , Ipomoea/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Folhas de Planta/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Contagem de Eritrócitos , Etanol , Feminino , Hemoglobinas/metabolismo , Infertilidade Masculina/induzido quimicamente , Masculino , Medicinas Tradicionais Africanas , Camundongos , Nigéria , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Solventes , Água
10.
Support Care Cancer ; 23(2): 333-41, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25082365

RESUMO

PURPOSE: Infertility is a frequent consequence of cancer therapy and is often associated with psychological distress. Although adult survivors prioritize fertility and parenthood, this issue remains unexplored among adolescent males. This study examined future fertility as a priority (relative to other life goals) at time of diagnosis for at-risk adolescents and their parents. METHODS: Newly diagnosed adolescent males (n = 96; age = 13.0-21.9 years) at increased risk for infertility secondary to cancer treatment prioritized eight life goals: to have school/work success, children, friends, wealth, health, a nice home, faith, and a romantic relationship. Patients' parents (fathers, n = 30; mothers, n = 61) rank-ordered the same priorities for their children. RESULTS: "Having children" was ranked as a "top 3" life goal among 43.8 % of adolescents, 36.7 % of fathers, and 21.3 % of mothers. Fertility ranked third among adolescents, fourth among fathers, and fifth among mothers. Future health was ranked the top priority across groups, distinct from all other goals (ps < 0.001), and fertility ranked higher than home ownership and wealth for all groups (ps < 0.001). For adolescents, low/moderate fertility risk perception was associated with higher fertility rankings than no/high risk perceptions (p = 0.01). CONCLUSIONS: Good health is the most important life goal among adolescents newly diagnosed with cancer and their parents. In this relatively small sample, adolescents prioritized fertility as a top goal, parents also rated fertility as being more important than home ownership and financial wealth. Health care providers should communicate fertility risk and preservation options at diagnosis and facilitate timely discussion among families, who may differ in prioritization of future fertility.


Assuntos
Pai/psicologia , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/psicologia , Mães/psicologia , Neoplasias/psicologia , Adolescente , Adulto , Feminino , Fertilidade , Serviços de Saúde , Humanos , Masculino , Pesquisa , Fatores Socioeconômicos , Bancos de Esperma , Inquéritos e Questionários , Sobreviventes/psicologia , Adulto Jovem
11.
Toxicol Sci ; 141(1): 278-91, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24973093

RESUMO

Men are at risk of becoming completely infertile due to innumerable environmental chemicals and pollutants. These xenobiotics, hence, should be tested for their potential adverse effects on male fertility. However, the testing load, a monumental challenge for employing conventional animal models, compels the pursuit of alternative models. Towards this direction, we show here that Drosophila melanogaster, an invertebrate, with its well characterized/conserved male reproductive processes/proteome, recapitulates male reproductive toxicity phenotypes observed in mammals when exposed to a known reproductive toxicant, dibutyl phthalate (DBP). Analogous to mammals, exposure to DBP reduced fertility, sperm counts, seminal proteins, increased oxidative modification/damage in reproductive tract proteins and altered the activity of a hormone receptor (estrogen related receptor) in Drosophila males. In addition, we show here that DBP is metabolized to monobutyl phthalate (MBP) in exposed Drosophila males and that MBP is more toxic than DBP, as observed in higher organisms. These findings suggest Drosophila as a potential alternative to traditional animal models for the prescreening of chemicals for their reproductive adversities and also to gain mechanistic insights into chemical-mediated endocrine disruption and male infertility.


Assuntos
Dibutilftalato/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Infertilidade Masculina/induzido quimicamente , Ácidos Ftálicos/toxicidade , Xenobióticos/toxicidade , Animais , Dibutilftalato/farmacocinética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Poluentes Ambientais/farmacocinética , Fertilidade/efeitos dos fármacos , Fertilidade/genética , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Masculino , Microscopia Confocal , Ácidos Ftálicos/farmacocinética , Reprodução/efeitos dos fármacos , Reprodução/genética , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Transcriptoma/efeitos dos fármacos , Xenobióticos/farmacocinética
12.
Reprod Toxicol ; 46: 56-63, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24632126

RESUMO

Trihalomethanes (THMs) have been demonstrated to adversely affect male reproductive health in animals, but the evidence in humans is limited. The study aimed to examine the association between THM exposure and semen quality in a Chinese population. We recruited 324 men from the same water supply district in Wuhan, China between April 2011 and May 2012. Exposure to THMs was evaluated based on their concentrations in tap water measured within 90 days preceding semen collection, the uptake factors of THMs and personal information on ingestion and showering/bathing. We found that TTHM [sum of chloroform (TCM) and brominated THMs (Br-THMs)], TCM and Br-THM uptakes via ingestion were associated with significant or suggestive decreasing trends in sperm concentration (P for trend=0.01, 0.03 and 0.05, respectively) and sperm count (P for trend=0.02, 0.05 and 0.09, respectively). Our results suggest that THM exposure via ingestion may adversely affect semen quality.


Assuntos
Sêmen/efeitos dos fármacos , Trialometanos/toxicidade , Poluentes Químicos da Água/toxicidade , Abastecimento de Água/análise , China/epidemiologia , Exposição Ambiental , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/epidemiologia , Masculino , Estudos Prospectivos , Fatores Socioeconômicos , Trialometanos/análise , Poluentes Químicos da Água/análise
13.
Toxicology ; 317: 6-16, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24447377

RESUMO

6:2 Fluorotelomer alcohol (6:2 FTOH) was evaluated for potential developmental and reproductive toxicity. 6:2 FTOH was administered by oral gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose at dosages of 5, 25, 125, or 250 mg/kg/day. The developmental toxicity study was performed in accordance with the Organization for Economic Development (OECD) Test Guideline 414, and the one-generation reproductive toxicity study was performed in accordance with the OECD Test Guideline 415. For the developmental toxicity study, adverse maternal toxicity observed at 250 mg/kg/day included reductions in body weight parameters and food consumption. Evidence of developmental toxicity was limited to increases in skeletal variations (ossification delays in the skull and rib alterations) at 250 mg/kg/day. There were no adverse maternal or developmental effects observed at 5, 25, or 125 mg/kg/day and there were no effects on reproductive outcome or quantitative litter data at any dose level. For the one-generation reproduction toxicity study, systemic parental and developmental toxicity were observed at 125 and 250 mg/kg/day. At 250 mg/kg/day, there was increased mortality among male and female parental rats, effects on body weight parameters, food consumption, and clinical signs, and there were effects on offspring survival indices and body weights. At 125 mg/kg/day, there was an increase in mortality in parental males only, and parental toxicity was limited to effects on body weight gain, food consumption (lactation), and clinical signs. Uterine weights were decreased at 125 and 250 mg/kg/day, although there were no corroborative histopathological changes. At 125 mg/kg/day, pup mortality was increased on lactation day 1, and body weights of the offspring were decreased during the second half of lactation. There was no evidence of either parental or developmental toxicity at 5 or 25mg/kg/day, and there were no effects on reproductive outcome at any dose level. Based on these data, 6:2 FTOH is not a selective reproductive or developmental toxicant at dosages that induce clear maternal/parental toxicity. Therefore, 6:2 FTOH would not be classified for reproductive/developmental toxicity under the United Nations' Globally Harmonized System of Classification and Labeling of Chemicals.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Hidrocarbonetos Fluorados/toxicidade , Infertilidade Feminina/induzido quimicamente , Infertilidade Masculina/induzido quimicamente , Exposição Materna/efeitos adversos , Octanóis/toxicidade , Exposição Paterna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Energia/efeitos dos fármacos , Feminino , Hidrocarbonetos Fluorados/administração & dosagem , Indicadores e Reagentes/administração & dosagem , Indicadores e Reagentes/toxicidade , Masculino , Nível de Efeito Adverso não Observado , Octanóis/administração & dosagem , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais , Redução de Peso/efeitos dos fármacos
14.
Birth Defects Res B Dev Reprod Toxicol ; 95(6): 410-20, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23213047

RESUMO

An outcome and statistical review of male reproductive performance assessed by including a mating phase within 6-month general toxicity studies in the Han Wistar rat was undertaken. The basic study design was 16-20 animals per group dosed for approximately 9 weeks before pairing the male rats with undosed females. This design provides opportunity for remating and automatically includes general toxicity parameters. The dose levels used in the 1- and 6-month studies show that male reproduction was assessed at generally similar doses. The majority of males (compound-dosed and controls) mated within 7 days. All vehicle-dosed males mated and 98.5% of these females were pregnant. Modeling shows that a pregnancy rate of less than 14 out of 16 pregnant animals is very unlikely to occur due to biological variability. Power calculations based on vehicle control data show that group sizes of >10 males have a >80% power of detecting a decrease in median of three embryos per group compared with the control group. Even if the number of pregnancies decreased by a third, a group size of ≥12 would still detect a decrement in the median of three embryos with >80% power. Based on the statistical modeling and inherent strengths of the study design, this review indicates that decrements in male reproductive function can be successfully detected by incorporating a mating phase into a 6-month rat study and that a group size of 12-16 is generally adequate rather than the 16-20 group size indicated as a generic default within ICHS5(R2).


Assuntos
Fertilidade/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Exposição Paterna , Testes de Toxicidade/métodos , Xenobióticos/toxicidade , Animais , Corpo Lúteo/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Modelos Estatísticos , Gravidez , Taxa de Gravidez , Ratos , Ratos Wistar
15.
Genet Test Mol Biomarkers ; 16(6): 592-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22304538

RESUMO

AIMS AND OBJECTIVES: Industrial workers are constantly exposed to benzene, especially at the production unit. The present investigation explores any association of the outcome of various reproductive malfunctions in terms of infertility and other related factors as a result of benzene exposure. METHODOLOGY: Blood and semen samples were collected from total 160 industrial workers exposed to benzene and 200 nonoccupationally exposed control subjects. We investigated macroscopic and microscopic semen parameters in the present study population. Body fluid benzene analysis was done by Head Space chromatography. The sperm DNA integrity was determined by modified alkaline single-cell gel electrophoresis or the comet assay method. RESULTS: No significant changes were observed in macroscopic semen parameters. A duration-dependent decrement in total sperm count and the percentage of motility was observed among the benzene-exposed industrial workers (p<0.05). A duration-dependent increment of abnormal sperm morphology was observed among the benzene-exposed industrial workers (p<0.01). A significant increase in comet tail length was observed in the exposed groups (p<0.01) in comparison to the controls. In regression analysis, the data were observed to be significant at the level of p<0.05 for Group II industrial workers (t=2.301). CONCLUSION: Sperm integrity is considered one of the major factors in male infertility. The sperm DNA damage is an important step from spermatogenesis to malfunctions such as infertility; therefore, the present study represents an important evaluation for correctly diagnosing the problem, precisely from the level of DNA itself.


Assuntos
Benzeno/efeitos adversos , Indústria Farmacêutica , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Exposição Ocupacional , Adulto , Benzeno/análise , Líquidos Corporais/química , Ensaio Cometa/métodos , Dano ao DNA , Humanos , Masculino , Sêmen/química , Sêmen/efeitos dos fármacos , Contagem de Espermatozoides , Espermatozoides/química , Espermatozoides/efeitos dos fármacos
16.
Syst Biol Reprod Med ; 58(1): 41-50, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22239080

RESUMO

Establishing specific biomarkers for the assessment of human male fertility status is an important goal to ensure the fitness of the male contribution so as to support the birth of a healthy child. Spermatozoa are considered an optimal surrogate tissue for the evaluation of spermatogenic function. Unlike the cells of the testis, spermatozoa do not require invasive procedures to procure a sample. A broad range of sperm biomarkers and tests have been described as useful for the assessment of the sperm function. However, these approaches appear limited considering the current state of the art of molecular diagnostics that could be developed for this purpose. In this review, we outline the suite of sperm biomarkers that are currently in use to assess human male fertility status. Their use as indicators of genotoxic exposure will be discussed.


Assuntos
Fertilidade , Infertilidade Masculina/diagnóstico , Análise do Sêmen , Espermatogênese , Espermatozoides/patologia , Aneuploidia , Biomarcadores/metabolismo , Forma Celular , Sobrevivência Celular , Montagem e Desmontagem da Cromatina , DNA/metabolismo , Dano ao DNA , Fertilidade/efeitos dos fármacos , Fertilidade/genética , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Mutagênicos/efeitos adversos , RNA/metabolismo , Medição de Risco , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo
17.
J Med Ethics ; 37(12): 747-51, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21670320

RESUMO

In a recent case in the UK, six men stored their sperm before undergoing chemotherapy treatment for cancer in case they proved to be infertile after the treatment. The sperm was not properly stored and as a result was inadvertently destroyed. The men sued the NHS Trust that stored the sperm and were in the end successful. This paper questions the basis on which the judgement was made and the rationale behind it, namely that the men 'had ownership' of the sperm, and that compensation was thus due on the grounds that the men's property had been destroyed. We first argue that the claim is erroneous and enhances the tendency towards the commodification of body parts. We then suggest that the men could have been compensated for the harm done to them without granting property rights, and that this would, at least in philosophical and ethical terms, have been more appropriate. To help illustrate this, we draw on a parallel case in French law in which a couple whose embryos had been destroyed were overtly denied ownership rights in them. Finally, we suggest some possible ethical and practical problems if the proprietary view expressed in the UK ruling were to become dominant in law, with particular focus on the storing of genetic information in biobanks. We conclude that, although compensation claims should not necessarily be ruled out, a 'no property in the body' approach should be the default position in cases of detached bodily materials, the alternative being significantly ethically problematic.


Assuntos
Compensação e Reparação/ética , Bancos de Esperma/legislação & jurisprudência , Mercantilização , Ética Médica , França , Corpo Humano , Direitos Humanos , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Imperícia/legislação & jurisprudência , Princípios Morais , Propriedade/ética , Propriedade/legislação & jurisprudência , Bancos de Esperma/normas , Espermatozoides , Medicina Estatal , Reino Unido
18.
Mol Nutr Food Res ; 55(4): 509-21, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21351250

RESUMO

Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 µg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs.


Assuntos
Carcinógenos/toxicidade , Compostos de Epóxi/toxicidade , Ésteres/toxicidade , Ácidos Graxos/química , Contaminação de Alimentos , Mutagênicos/toxicidade , Propanóis/toxicidade , alfa-Cloridrina/toxicidade , Animais , Biotransformação , Carcinógenos/administração & dosagem , Carcinógenos/química , Carcinógenos/farmacocinética , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/química , Compostos de Epóxi/farmacocinética , Ésteres/administração & dosagem , Ésteres/química , Ésteres/farmacocinética , Feminino , Humanos , Infertilidade Masculina/induzido quimicamente , Masculino , Mutagênicos/administração & dosagem , Mutagênicos/química , Mutagênicos/farmacocinética , Neoplasias/induzido quimicamente , Óleos de Plantas/efeitos adversos , Óleos de Plantas/química , Propanóis/administração & dosagem , Propanóis/química , Propanóis/farmacocinética , Insuficiência Renal/induzido quimicamente , Medição de Risco , alfa-Cloridrina/administração & dosagem , alfa-Cloridrina/análise , alfa-Cloridrina/farmacocinética
19.
J Pediatr Oncol Nurs ; 23(4): 182-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16766683

RESUMO

The impressive increase in the survival rate of childhood cancer patients has produced increased interest in quality of life issues. This research addresses nurse practice issues in determining whether the newly diagnosed adolescent male patient is offered the option of sperm banking before undergoing chemotherapy treatment. Questionnaires were distributed to nurses and nurse practitioners on 3 inpatient and outpatient units who care for adolescent male cancer patients at the time of diagnosis, during chemotherapy, and during follow-up care. Findings indicate that 96.3% of respondents agreed that all male patients undergoing cancer treatment with infertility as a potential side effect should be offered sperm banking. Respondents viewed oncologists and nurse practitioners as appropriate professionals to discuss the option. Lack of knowledge regarding sperm banking could be limiting nurses' willingness to introduce the topic, and education regarding cryopreservation may improve their knowledge and practice.


Assuntos
Antineoplásicos/efeitos adversos , Atitude do Pessoal de Saúde , Infertilidade Masculina/induzido quimicamente , Profissionais de Enfermagem/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Bancos de Esperma , Adolescente , Competência Clínica , Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Infertilidade Masculina/psicologia , Infertilidade Masculina/terapia , Inseminação Artificial Homóloga , Masculino , Profissionais de Enfermagem/educação , Papel do Profissional de Enfermagem/psicologia , Relações Enfermeiro-Paciente , Pesquisa Metodológica em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/educação , Enfermagem Oncológica/educação , Enfermagem Oncológica/organização & administração , Educação de Pacientes como Assunto/organização & administração , Qualidade de Vida , Sudeste dos Estados Unidos , Inquéritos e Questionários , Sobreviventes/psicologia
20.
Contraception ; 72(4): 308-13, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16181977

RESUMO

Male reproductive toxicity involves a broad range of targets and mechanisms such as direct effects on the seminiferous epithelium and/or on Leydig and Sertoli cells supporting spermatogenesis, epididymal sperm maturation as well as endocrine disruption. Direct effects on spermatogenesis may be adequately revealed through both reproduction and repeated-dose toxicity studies; however, more research is needed on early markers of effect and on long-term sequelae of short-term exposures. Endocrine-related mechanisms are particularly relevant to subtle, but persistent effects on reproductive development due to altered early programming; the two-generation study is the test of choice, whereas targeted studies on the prepubertal phase are also desirable. Studies using in vitro methods as well as toxicogenomics are increasing; although gaps exist and much validation work is needed, in perspective, such approaches may be important in order to select compound, understand mechanisms, as well identify biomarkers of potential use also in human studies.


Assuntos
Infertilidade Masculina/induzido quimicamente , Biomarcadores , Disruptores Endócrinos/toxicidade , Humanos , Células Intersticiais do Testículo/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Medição de Risco , Células de Sertoli/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade
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