Expression profiles of meiotic genes in male vs. female gonads and gametes : insights into fertility issues

Gametes are specialized cells that, at fertilization, give rise to a totipotent zygote capable of generating an entire organism. Female and male germ cells undergo meiosis to produce mature gametes; however, sex-specific events of oogenesis and spermatogenesis contribute to specific roles of gametes in reproductive issues. We investigate the differential gene expression (DGE) of meiosis-related genes in human female and male gonads and gametes in normal and pathological conditions. The transcriptome data for the DGE analysis was obtained through the Gene Expression Omnibus repository, comprising human ovary and testicle samples of the prenatal period and adulthood, additionally to male (nonobstructive azoospermia (NOA) and teratozoospermia), and female (polycystic ovary syndrome (PCOS) and advanced maternal age) reproductive conditions. Gene ontology terms related to meiosis were associated with 678 genes, of which 17 genes in common were differentially expressed between the testicle and ovary during the prenatal period and adulthood. Except for SERPINA5 and SOX9, the 17 meiosis-related genes were downregulated in the testicle during the prenatal period and upregulated in adulthood compared to the ovary. No differences were observed in the oocytes of PCOS patients; however, meiosis-related genes were differentially expressed according to the patient’s age and maturity of the oocyte. In NOA and teratozoospermia, 145 meiosis-related genes were differentially expressed in comparison to the control, including OOEP; despite no recognized role in male reproduction, OOEP was co-expressed with genes related to male fertility. Taking together, these results shed light on potential genes that might be relevant to comprehend human fertility disorders

A Genética na Fibrose Cística

A fibrose cística (FC) é a doença autossômica recessiva mais comum em euro-descendentes, com uma incidência estimada de 1 caso a cada 2.500 nascimentos. A FC é uma doença multissistêmica, caracterizada principalmente por doença pulmonar progressiva, disfunção pancreática exócrina e concentração elevada de eletrólitos no suor. O gene associado a essa doença é denominado CFTR e se localiza no cromossomo 7, sendo dividido em 27 éxons. Até o momento, mais de 1.800 variações de sequência foram identificadas no gene CFTR, sendo que a mutação p.Phe508del é a mais frequente entre os pacientes de FC. No Brasil, a frequência dessa mutação não é tão elevada, devido provavelmente à miscigenação e, consequentemente, o locus CFTR apresenta maior heterogeneidade alélica. A probabilidade de um filho afetado com FC é de 1 em 4, ou 25%, para filhos de um casal em que ambos são portadores de uma mutação.  O risco de um indivíduo com FC ter filhos afetados depende de seu parceiro – se o parceiro for portador da doença o risco será de 50%. Para casais em risco de terem filhos com FC e com mutação ou mutações identificadas, é possível oferecer diagnóstico pré-natal (DPN) e diagnóstico genético pré-implantacional (DPI). Considerando a complexidade da informação genética relacionada à FC e das alternativas reprodutivas que estão surgindo, é muito importante a disponibilização do aconselhamento genético para o paciente e sua família

Riscos reprodutivos em região próxima ao pólo petroquímico de Triunfo no Sul do Brasil

OBJECTIVE: To evaluate possible adverse reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil. METHODS: A review of 17,113 birth records of the main hospital of the municipality of Montenegro, southern Brazil, from 1983 to 1998 was carried out. Three groups of cases were selected: (1) newborns with major congenital malformations; (2) newborns with low birth weight (;500 g). A control was assigned to each case. Controls were the first newborns weighing >; or = 2,500 g without malformations and of case-matching sex. Mother's residence during pregnancy was used as an exposure parameter. Statistical analyses were performed using Chi-square test or Fisher test, odds ratio, 0.05 significance level, and 95% confidence interval. RESULTS: For unadjusted analysis, it was found a correlation between low birth weight and geographical proximity of mother's residence to the petrochemical plant (OR = 1.66; 95% CI = 1.01--2.72) or residence on the way of preferential wind direction (OR = 1.62; 95% CI = 1.03--2.56). When other covariates were added in the conditional logistic regression (maternal smoking habits, chronic disease and age), there was no association. CONCLUSIONS: Despite final results were negative, low birth weight could be a good parameter of environmental contamination and should be closely monitored in the studied area.OBJETIVO: Avaliar os possíveis riscos reprodutivos em uma região próxima a pólo petroquímico situado no Rio Grande do Sul. MÉTODOS: Foram analisados 17.113 registros de nascimentos ocorridos no principal hospital da região, localizado no município de Montenegro, RS, desde 1983 até 1998. Foram selecionados três diferentes grupos de casos: (1) recém-nascidos portadores de malformações congênitas maiores; (2) recém-nascidos com baixo peso ao nascer (;500 g). Para cada caso, foi atribuído um controle específico, que foi a primeira criança nascida viva, pesando 2.500 g ou mais, com ausência de malformações e tendo o mesmo sexo que o caso em questão. A residência materna durante a gravidez foi utilizada como um parâmetro para exposição. Para a análise estatística, foram usados os testes qui-quadrado ou Fisher, "odds ratio", nível de significância de 0,05 e intervalo de confiança de 95%. RESULTADOS: Foi encontrada correlação positiva para baixo peso ao nascer e para proximidade geográfica da residência materna ao Pólo Petroquímico ["odds ratio" (OR) = 1,66; 95% confidence interval (CI) = 1,01-2,72] ou residência na direção preferencial do vento ["odds ratio" (OR) = 1,62; 95% confidence interval (CI) = 1,03-2,56]. Quando outras variáveis foram incluídas na análise de regressão logística condicional (fumo, doenças crônicas e idade materna), essa associação desapareceu. CONCLUSÕES: Apesar de os resultados finais terem sido negativos, o baixo peso ao nascer pode ser um bom parâmetro para medir a contaminação ambiental, mas deve ser monitorado na região estudada

High-risk twin pregnancy : case report of an adolescent patient with cystic fbrosis and systemic lupus erythematosus

Background: We present the frst case to our knowledge of a spontaneous twin pregnancy in a 16-year-old Caucasian patient with cystic fbrosis and systemic lupus erythematosus. Cystic fbrosis is one of the most common autosomal recessive genetic disorders and primarily afects the respiratory and digestive systems. Systemic lupus erythematosus is a chronic infammatory disease of unknown cause that afects nearly every organ. Patients with cystic fbrosis or systemic lupus erythematosus are progressively having longer life expectancy and better quality of life, which has led a greater number of female patients reporting the desire to become mothers. Case presentation: We present a case of a Caucasian 16-year-old pregnant with twins being treated for both cystic fbrosis and systemic lupus erythematosus. She has two CFTR mutations: p.F508del and 1812_1G>A. In the second trimester, she was admitted for possible preterm labor, which was successfully stopped. The patient’s nutritional status worsened, and she had a pulmonary exacerbation as well as a fare of systemic lupus erythematosus. At the 28th gestational week, she presented with a massive hemoptysis episode. The cesarean delivery had no complications, and there were no serious immediate postpartum complications. Discussion and conclusions: While adolescent pregnancies in and of themselves are considered high risk for both the young mothers and their children, they are further complicated when the mother has two chronic diseases and a twin pregnancy. We achieved positive results using a multidisciplinary approach; however, the risks involved were so high that major eforts are to be taken by our medical community to prevent unplanned pregnancies in all patients with cystic fbrosis, especially when a serious comorbidity like the one in this case is present

Thalidomide Analogs in Brazil: Concern About Teratogenesis

It has been more than 50 years since thalidomide was withdrawn from the world market due to its teratogenic potential. However, its widespread use around the world resumed due to its immunomo-dulatory and anti-angiogenic properties. The drug established itself in new therapies, and interest continued with the emergence of more potent analogs, the most notable being lenalidomide and pomalidomide, which are not approved in Brazil. The question that arises after analog synthesis is: Do these drugs also have the same teratogenic potential? The answer to this question is based only on experimental studies because exposure to humans is not authorized and has not yet been descri-bed. Although thalidomide has been recognized as a powerful human teratogen for many years, its molecular mechanisms of teratogenesis remain to be fully explained. Efforts with animal models and human genetic studies have clarified some important pathways that are most likely involved in the teratogenic action of thalidomide. However, it has not yet been possible to identify the teratogenic domain of the molecule from the therapeutic ones. Moreover, there are species-specific differences that must be taken into consideration when teratogenicity is evaluated.Título PT: Análogos da Talidomida no Brasil: Preocupação com a TeratogêneseFaz mais de 50 anos que a talidomida foi retirada do mercado mundial devido ao seu potencial teratogênico. Entretanto, seu uso disseminado em todo o mundo foi retomado devido às suas propriedades imunomodulatórias e antiangiogênicas. A droga foi utilizada em novas terapias e o interesse continuou com a emergência de análogos mais potentes, os mais notáveis deles sendo a lenalidomida e a pomalidomida, que não estão aprovados no Brasil. A questão que surge após a síntese dos análogos é: Estas drogas também têm o mesmo potencial teratogênico? A resposta a esta pergunta baseia-se apenas em estudos experimentais, pois a exposição a humanos não está autorizada e ainda não foi reporta-da. Embora a talidomida tenha sido durante muitos anos reconhecida como um poderoso teratógeno humano, os mecanismos moleculares da teratogênese ainda não foram com-pletamente explicados. Os esforços com modelos animais e estudos genéticos humanos para entender o efeito tóxico da droga esclareceram alguns importantes caminhos que estão muito provavelmente envolvidos na ação teratogênica. Entretanto, ainda não foi possível isolar o agente teratogênico das outras ações terapêuticas na talidomida e seus análogos. Além disso, há diferenças específicas da espécie que devem ser levadas em consideração quando a teratogenicidade é avaliada

Assessment of genomic changes in a CRISPR/Cas9 Phaeodactylum tricornutum mutant through whole genome resequencing

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, co-opted from a bacterial defense natural mechanism, is the cutting edge technology to carry out genome editing in a revolutionary fashion. It has been shown to work in many different model organisms, from human to microbes, including two diatom species, Phaeodactylum tricornutum and Thalassiosira pseudonana. Transforming P. tricornutum by bacterial conjugation, we have performed CRISPR/Cas9-based mutagenesis delivering the nuclease as an episome; this allowed for avoiding unwanted perturbations due to random integration in the genome and for excluding the Cas9 activity when it was no longer required, reducing the probability of obtaining off-target mutations, a major drawback of the technology. Since there are no reports on off-target occurrence at the genome level in microalgae, we performed whole-genome Illumina sequencing and found a number of different unspecific changes in both the wild type and mutant strains, while we did not observe any preferential mutation in the genomic regions in which off-targets were predicted. Our results confirm that the CRISPR/Cas9 technology can be efficiently applied to diatoms, showing that the choice of the conjugation method is advantageous for minimizing unwanted changes in the genome of P. tricornutum