BackgroundAlthough males contribute half of the embryo’s genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter’s breast cancer risk has been examined in few studies.MethodsMale Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis.ResultsCompared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers’ sperm and their daughters’ mammary glands, and to modifications in breast cancer-related protein expression in this tissue.ConclusionsOur findings highlight the importance of paternal nutrition in affecting future generations’ risk of developing breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0729-x) contains supplementary material, which is available to authorized users.

The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl 2 ; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl 2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P¼ 0·003), serum testosterone levels (P¼0·001), the relative weight of epididymis (P¼ 0·013) and ventral prostate (P¼0·052), the percentage of normal sperm (P¼ 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P¼0·001) and of testicular levels of glutathione (P¼0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms. Key words: Functional foods: Reproduction: CadmiumCadmium is a metal found in nature in low concentrations (1) .However, high levels of the metal can be found in the environment due to the burning of fossil fuels, the manufacture of batteries and the production of pigments and stabilisers (2) . The consequent contamination of soil and water results in the exposure of plants and animals to the metal and its bioaccumulation (3,4) . Moreover, tobacco smoke is another major source of human exposure to cadmium (5) .In the male reproductive system, cadmium is known to impair reproductive physiology and decrease sperm quality (6,7) . In addition, in vitro studies have shown that cadmium can stimulate Sertoli cell apoptosis, leading to the disruption of the blood -testis barrier (8,9) . Endocrine disruption is another consequence of cadmium exposure, caused by Leydig cell apoptosis and decreased serum levels of testosterone, as demonstrated in animal studies (10,11) . Clinical trials haveshown an inverse correlation between high serum levels of cadmium and semen quality, including sperm DNA damage, sperm count, motility and morphology (12 -15) . Oxidative stress is related to cadmium-induced damage, increasing the...

2012 AgradecimentosSe chego agora a bom porto, foi porque não viajei sozinha.Quero, por isso, agradecer, Aos meus cavalos-marinhos, os protagonistas desta aventura.Aos meus orientadores, por me terem aberto a porta da Guia. Ao Rui, pela confiança nesta jovem aprendiz, pela paciência de guiar quem dá os primeiros passos no mundo da Ciência. Ao Luís, pelos conselhos experientes que fizeram daquele forte uma casa para os cavalos-marinhos.A todos no Laboratório da Guia, pelo companheirismo e disponibilidade. Em especial à Marta e à Filipa, por toda a ajuda, desde o início. E ao Tiago, por ser ele próprio, o cientista desenrascado, com uma solução para tudo, e que tantas vezes me salvou.Aos meus colegas de mestrado, por estarmos todos no mesmo barco, onde não faltou o espírito de entreajuda, à Rita, ao Manel, à Vanessa. E em especial à Kuka. Pela paixão contagiante que tem pela Ciência. Pela mão amiga, sempre por perto, sempre pronta. Por ter estado sempre lá, nos incontáveis cafés no terraço, nas viagens de comboio, nas discussões académicas e nas piadas mais tolas. Por toda a confiança. Obrigada.Aos Amigos, aos "mais fixes", aos biólogos e aos outros, aos que estiveram perto, e aos que estando longe estiveram sempre comigo. Aos da "vila" e aos de fora, de Portugal e arredores.Aos de infância e aos de universidade. Aos Professores. Aos escuteiros, com quem aprendi a tirar o "im" de "impossível". Aos que estiveram pouco tempo, e aos que sem saber vão estar para sempre. Porque cada um me deu algo que me fez chegar aqui.Ao Eduardo, por me ouvir, e por falar. Por ser a constância em dias mais tempestuosos.Por acreditar sempre. À minha Família. Aos meus Pais, por tudo.Por me ensinarem a amar a Natureza, a olhá-la para lá do que se vê, e a querer descobrir os seus mistérios. Às minhas irmãs, pela amizade que nunca acaba, e que cresce connosco.

Introduction: Hypoglycemia leading to hospitalization is associated with adverse economic outcomes, although the real burden is unknown. The HIPOS-WARD (Hypoglycemia In Portugal Observational Study-Ward) aimed to characterize ward admissions due to hypoglycemia episodes in treated patients with diabetes and assess their economic impact to the National Health System. Methods: Observational, cross-sectional study, conducted in 16 Portuguese centers for 22 months. The applied microcosting approach was based on healthcare resource data, collected from patients' charts upon ward admission until discharge, and unitary costs from official/ public data sources. Absenteeism was also Digital Features To view digital features for this article go to

Background We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications. Methods In this cross-sectional, multicentered study, the observational data was collected by physicians from patient’s hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level. Results There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001). Conclusions Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.