Browsing by Author "Barros, A."
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- Genetic variants of CYP2C9 and IL-6 on female infertilityPublication . Cardoso, R.; Gonçalves, A.; da Silva, J.M.; Oliveira, C.; Xavier, P.; Alves, H.; Barros, A.; Botelho, M.C.AIM: To study the polymorphic variants in CYP2C9*2*3 and the C-174G promoter polymorphism of the IL-6 gene on Infertile Women.BACKGROUND: - Infertility affects 15–20% of couples worldwide. Within the past decades, there has been a steady rise in the treatment of female infertility with several drugs; - The cytochrome P450 (CYP) genes are oxygenases involved in estrogen biosynthesis and metabolism, generation of DNA damaging procarcinogens, and response to anti-estrogen therapies used in female infertility treatments: - Interleukin-6 (IL-6) is a pleiotropic proinflammatory cytokine, highly expressed in the female urogenital tract and reproductive organs. It has been implicated in estrogen metabolism imbalance.
- Rare double sex and mab-3-related transcription factor 1 regulatory variants in severe spermatogenic failurePublication . Lima, A.C.; Carvalho, F.; Gonçalves, J.; Fernandes, S.; Marques, P.I.; Sousa, M.; Barros, A.; Seixas, A.; Amorim, A.; Conrad, D.F.; Lopes, M.The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates and is known to play an essential role in gonadal development and maintenance of spermatogenesis in mice. In humans, the genomic region harboring the DMRT gene cluster has been implicated in disorders of sex development and recently DMRT1 deletions were shown to be associated with non-obstructive azoospermia (NOA). In this work, we have employed different methods to screen a cohort of Portuguese NOA patients for DMRT1 exonic insertions and deletions [by multiplex ligation probe assay (MLPA); n = 68] and point mutations (by Sanger sequencing; n = 155). We have found three novel patient-specific non-coding variants in heterozygosity that were absent from 357 geographically matched controls. One of these is a complex variant with a putative regulatory role (c.-223_-219CGAAA>T), located in the promoter region within a conserved sequence involved in Dmrt1 repression. Moreover, while DMRT1 domains are highly conserved across vertebrates and show reduced levels of diversity in human populations, two rare synonymous substitutions (rs376518776 and rs34946058) and two rare non-coding variants that potentially affect DMRT1 expression and splicing (rs144122237 and rs200423545) were overrepresented in patients when compared with 376 Portuguese controls (301 fertile and 75 normozoospermic). Overall our previous and present results suggest a role of changes in DMRT1 dosage in NOA potentially also through a process of gene misregulation, even though DMRT1 deleterious variants seem to be rare.
- Urinary Estrogen Metabolites and Self-Reported Infertility in Women Infected with Schistosoma haematobiumPublication . Santos, J.; Gouveia, M.J.; Vale, N.; Delgado, M. de L.; Gonçalves, A.; da Silva, J.M.; Oliveira, C.; Xavier, P.; Gomes, P.; Santos, L.L.; Lopes, C.; Barros, A.; Rinaldi, G.; Brindley, P.J.; da Costa, J.M.; Sousa, M.; Botelho, M.C.Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens.