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Ferreira C.,University of Porto | Ferreira C.,Royal University | Sousa M.,University of Porto | Sousa M.,Center For Reproductive Genetics Prof Alberto Barros | And 5 more authors.
Current Pharmaceutical Design | Year: 2015

Male infertility has been increasing over the last decades being nowadays a pressing health problem. Diabetes mellitus (DM) can contribute directly or indirectly to male infertility due to an abnormal spermatogenesis, which results in a decreased sperm quality. Type 2 Diabetes mellitus (T2DM) is responsible for the vast majority of DM cases, being frequently treated with oral antidiabetic drugs. Metformin is the most cost-effective therapy for the treatment of T2DM. This biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels. The main metabolic action of this drug occurs in the liver. However, it has been shown that metformin acts on a variety of organs including the male reproductive system. With the rising numbers of diabetic individuals among younger populations, there is an increase in the consumption of metformin in individuals of this age group. As a result, it is important to discuss the role of metformin in male fertility. This review presents the most recent data available from studies on the effects of metformin on male reproductive system. Together with the discussion of these effects, their significance to male fertility is also debated. © 2015 Bentham Science Publishers.

Martins A.D.,University of Beira Interior | Martins A.D.,University of Porto | Moreira A.C.,University of Porto | Sa R.,University of Porto | And 9 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2015

Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50. ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility. © 2015 Elsevier B.V.

Rabaca A.,University of Porto | Sousa M.,University of Porto | Sousa M.,Center For Reproductive Genetics Prof Alberto Barros | Alves M.G.,University of Beira Interior | And 3 more authors.
Current Medicinal Chemistry | Year: 2015

Cancer has been affecting a growing number of children, adolescents and adult males in reproductive age. Male reproductive potential is adversely affected by chemothera-peutic drugs and patients are at risk for prolonged infertility. Fertility recovery is related to the chemothera-peutic agent and dosage used, being thus difficult to predict. As a result, there is a strong need to identify a natural or synthetic compound that is able to preserve male fertility without interfering with the efficacy of the chemotherapeutic regimen. New procedures, as well as several drugs, are being investigated to assess their efficiency in protecting male reproductive functions from the chemotherapy side-effects. This review provides an overview of the wide range of chemotherapeutic drugs regularly used in cancer treatment and their detrimental effects on male fertility. In addition, it also assesses the existing protector agents for male fertility and their usefulness in preserving and protecting male reproductive functions exposed to chemotherapeutics. Several protector agents for male fertility are being studied, and results are promising. Nonetheless, further research must be implemented to identify a supplemental therapy that addresses the multiple side effects of chemotherapy on male reproductive function. Until such therapy is discovered, it is fundamental that all fertility preservation options are discussed with patients, before treatment is initiated, to assure parenthood. © 2015 Bentham Science Publishers.

Botelho M.C.,National Institute Of Health Dr Ricardo Jorge | Botelho M.C.,University of Porto | Alves H.,National Institute Of Health Dr Ricardo Jorge | Barros A.,Center For Reproductive Genetics Prof Alberto Barros | And 4 more authors.
Trends in Parasitology | Year: 2015

Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. Schistosomiasis haematobia also appears to negatively influence fertility, and is particularly associated with female infertility. Given that estrogens and estrogen receptors are key players in human reproduction, we speculate that schistosome estrogen-like molecules may contribute to infertility through hormonal imbalances. Here, we review recent findings on the role of estrogens and estrogen receptors on both carcinogenesis and infertility associated with urogenital schistosomiasis and discuss the basic hormonal mechanisms that might be common in cancer and infertility. © 2015 Elsevier Ltd.

Almeida S.,University of Porto | Alves M.G.,University of Beira Interior | Sousa M.,University of Porto | Sousa M.,Center For Reproductive Genetics Prof Alberto Barros | And 2 more authors.
Neurotoxicity Research | Year: 2016

Life expectancy of most human populations has greatly increased as a result of factors including better hygiene, medical practice, and nutrition. Unfortunately, as humans age, they become more prone to suffer from neurodegenerative diseases and neurotoxicity. Polyphenols can be cheaply and easily obtained as part of a healthy diet. They present a wide range of biological activities, many of which have relevance for human health. Compelling evidence has shown that dietary phytochemicals, particularly polyphenols, have properties that may suppress neuroinflammation and prevent toxic and degenerative effects in the brain. The mechanisms by which polyphenols exert their action are not fully understood, but it is clear that they have a direct effect through their antioxidant activities. They have also been shown to modulate intracellular signaling cascades, including the PI3K–Akt, MAPK, Nrf2, and MEK pathways. Polyphenols also interact with a range of neurotransmitters, illustrating that these compounds can promote their health benefits in the brain through a direct, indirect, or complex action. We discuss whether polyphenols obtained from diet or food supplements are an effective strategy to prevent or treat neurodegeneration. We also discuss the safety, mechanisms of action, and the current and future relevance of polyphenols in clinical treatment of neurodegenerative diseases. As populations age, it is important to discuss the dietary strategies to avoid or counteract the effects of incurable neurodegenerative disorders, which already represent an enormous financial and emotional burden for health care systems, patients, and their families. © 2016 Springer Science+Business Media New York

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