RESUMO

Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene single nucleotide polymorphisms (SNPs) have been associated with RPL. The frequency of some SNPs is increased in women suffering from RLP from Asian or Caucasian races; however, in admixed populations, the information on possible genetic links is scarce and contradictory. This study aimed to assess the frequency of two SNPs present in two different enzymes involved in medical conditions observed during pregnancy. It is a case-control study. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics, is present in the ovaries, and is hormonally regulated. The endothelial nitric oxide synthase (NOS3) that forms nitric is involved in vascular tone. Two SNPs, rs1051740 (mEPH) and rs1799983 (NOS3), were assessed. The study included 50 controls and 63 primary RPL patients. The frequency of mutated alleles in both SNPs was significantly higher in patients (p < 0.05). Double-mutated homozygotes were encountered only in RPL patients (p < 0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

RESUMO

Systemic lupus erythematosus is a debilitating autoimmune disease characterized by uncontrolled activation of adaptive immunity, particularly B cells, which predominantly affects women in a 9 to 1 ratio compared to men. This stark sex disparity strongly suggests a role for female sex hormones in the disease's onset and progression. Indeed, it is widely recognized that estradiol not only enhances the survival of autoreactive B cells but also stimulates the production of autoantibodies associated with systemic lupus erythematosus, such as anti-nuclear antibodies and anti-dsDNA antibodies. Clinical manifestations of systemic lupus erythematosus typically emerge after puberty and persist throughout reproductive life. Furthermore, symptoms often exacerbate during the premenstrual period and pregnancy, as increased levels of estradiol can contribute to disease flares. Despite being fertile, women with lupus face a heightened risk of pregnancy-related complications, including pregnancy loss and stillbirth, which significantly surpass the rates observed in the healthy population. Therefore, this review aims to summarize and discuss the existing literature on the influence of female sex hormones on B-cell activation in patients with systemic lupus erythematosus, with a particular emphasis on their impact on pregnancy loss.

Assuntos

RESUMO

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a challenge as it necessitates considerations for the well-being of both the mother and the developing fetus. Diagnosis can be challenging and is often an incidental finding during routine imaging, which can lead to difficult decision-making. The choice of the ideal imaging study in these cases is a matter of debate. When the tumor is detected at an early stage, radical nephrectomy is indicated. However, there is still controversy regarding whether it should be performed conventionally or laparoscopically, as both techniques have their risks and benefits. In this context, our primary objective was to provide adequate surgical treatment for the patient, while safeguarding fetal health. Here, we present a patient with a history of recurrent miscarriages, in whom a renal tumor was incidentally diagnosed during pregnancy. Adding to the uniqueness of this case, the patient was diagnosed with an eosinophilic variant of chromophobe RCC through histopathological analysis. Our aim is to highlight the controversies surrounding diagnostic and treatment methodologies and to present the surgical techniques employed in this unique situation. This case underscores the importance and need for a multidisciplinary approach, which, in our instance, resulted in favorable outcomes for both maternal and neonatal health.

RESUMO

Recurrent pregnancy loss (RPL) occurs in approximately 5% of women. Despite an abundance of evidence, the molecular mechanism of RPL's pathology remains unclear. Here, we report the protective role of polo-like kinase 1 (PLK1) during RPL. We aimed to construct an RPL network utilizing GEO datasets and identified hub high-traffic genes. We also investigated whether the expressions of PLK1 were altered in the chorionic villi collected from women with RPL compared to those from healthy early pregnant women. Gene expression differences were evaluated using both pathway and gene ontology (GO) analyses. The identified genes were validated using in vivo and in vitro models. Mice with PLK1-overexpression and PLK1-knockdown in vitro models were produced by transfecting certain plasmids and si-RNA, respectively. The apoptosis in the chorionic villi, mitochondrial function, and NF-κB signaling activity was evaluated. To suppress the activation of PLK1, the PLK1 inhibitor BI2536 was administered. The HTR-8/SVneo and JEG-3 cell lines were chosen to establish an RPL model in vitro. The NF-κB signaling, Foxo signaling, PI3K/AKT, and endometrial cancer signaling pathways were identified via the RPL regulatory network. The following genes were identified: PLK1 as hub high-traffic gene and MMP2, MMP9, BAX, MFN1, MFN2, FOXO1, OPA1, COX15, BCL2, DRP1, FIS1, TRAF2, and TOP2A. Clinical samples were examined, and the results demonstrated that RPL patients had tissues with decreased PLK1 expression in comparison to women with normal pregnancies (p < 0.01). In vitro, PLK1 knockdown induced the NF-κB signaling pathway and apoptosis activation while decreasing cell invasion, migration, and proliferation (p < 0.05). Furthermore, the in vivo model proved that cell mitochondrial function and chorionic villi development are both hampered by PLK1 suppression. Our findings revealed that the PLK1/TRAF2/NF-κB axis plays a crucial role in RPL-induced chorionic villi dysfunction by regulating mitochondrial dynamics and apoptosis and might be a potential therapeutic target in the clinic.

RESUMO

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Assuntos

RESUMO

Resumen OBJETIVO: Determinar la prevalencia de los principales factores etiológicos de pérdida gestacional recurrente en la población de un hospital de tercer nivel de atención. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo llevado a cabo en pacientes con protocolo de estudio de dos o más pérdidas gestacionales recurrentes que iniciaron el control prenatal en el servicio de Obstetricia o que ingresaron al Instituto Nacional de Perinatología con diagnóstico de infertilidad entre los meses de enero de 2017 a enero de 2020. En cada grupo se revisaron los factores etiológicos descritos en la bibliografía internacional como posibles causas de pérdida gestacional recurrente. RESULTADOS: Se estudiaron 280 pacientes y el factor con mayor prevalencia de pérdida gestacional recurrente fue el endocrino con el 56.78% (n = 159), seguido del anatómico-uterino con el 42.14% (n = 118) y en tercer lugar el infeccioso con 40.35% (n = 113). En las 75 pacientes del grupo de infertilidad, el factor etiológico más prevalente fue el endocrino (88%; n = 66), seguido del anatómico-uterino (53.3%; n = 40) y a continuación del masculino (50.6%; n = 38). En las pacientes del grupo de Obstetricia, el factor con mayor prevalencia fue el endocrino (45.36%; n = 93), seguido del anatómico-uterino (38.04%; n = 78) y el infeccioso (37%; n = 76). CONCLUSIONES: Los factores relacionados con la pérdida gestacional recurrente, descritos en la bibliografía internacional y analizados en este estudio, mostraron prevalencias similares en población institucional. Las que difieren están influidas por las características de la población estudiada, los recursos de la institución e, incluso, el diagnóstico y servicio por el que ingresaron como pacientes al INPer.

Abstract OBJECTIVE: To determine the prevalence of the main etiological factors of recurrent gestational loss in the population of a tertiary care hospital. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive study carried out in patients with study protocol of two or more recurrent gestational losses who initiated prenatal control in the Obstetrics service or who were admitted to the Instituto Nacional de Perinatologia with a diagnosis of infertility between the months of January 2017 to January 2020. In each group, the etiological factors described in the international literature as possible causes of recurrent gestational loss were reviewed. RESULTS: 280 patients were studied and the factor with the highest prevalence of recurrent gestational loss was endocrine with 56.78% (n = 159), followed by anatomic-uterine with 42.14% (n = 118) and thirdly infectious with 40.35% (n = 113). In the 75 patients in the infertility group, the most prevalent etiologic factor was endocrine (88%; n = 66), followed by anatomic-uterine (53.3%; n = 40) and then male (50.6%; n = 38). In patients in the obstetrics group, the factor with the highest prevalence was endocrine (45.36%; n = 93), followed by anatomic-uterine (38.04%; n = 78) and infectious (37%; n = 76). CONCLUSIONS: The factors related to recurrent gestational loss, described in the international literature and analyzed in this study, showed similar prevalences in institutional population. Those that differ are influenced by the characteristics of the population studied, the resources of the institution and, even, the diagnosis and service for which they were admitted as patients to the INPer.

RESUMO

Abstract Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL). Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification. Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; theMallele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj]=2.07; 95% confidence interval [CI]; p<0.001). However, regarding PON1 Q192R, the R mutated allele frequency was found in 28.5% in RPL and in 33% in controls. The R allele did not show any risk for RPL (ORadj 0.81; 95%CI; p=0.329). Conclusion The present study suggests that there is an effect of genetic polymorphism on RPL and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in the uterus.

Resumo Objetivo O objetivo deste estudo foi examinar a relação entre os polimorfismos PON1 e perda recorrente de gravidez PRG. Métodos Em um estudo transversal, foramcoletadas amostras de sangue de 100 mulheres. O DNA foi extraído e os genótipos PON1 foram determinados por amplificação por PCR. Resultados Com relação ao PON1 L55M, a frequência do alelo mutado (M) foi encontrada em 70,5% no PRG e em 53,5% nos controles; o alelo M foi significativamente associado a um risco aumentado de PRG (odds radio ajustado [ORadj] =2,07; intervalo de confiança [IC] 95%; p<0,001). No entanto, em relação ao PON1 Q192R, a frequência do alelo mutado R foi encontrada em 28,5% no PRG e em 33% nos controles. O alelo R não mostrou qualquer risco para PRG (ORadj 0,81; IC 95; p=0,329). Conclusão O presente estudo sugere que há um efeito do polimorfismo genético sobre PRG e fornece evidências adicionais que se combinam com as informações crescentes sobre asmaneiras pelas quais certos genótipos PON1 podemafetar o desenvolvimento do feto no útero.

Assuntos

RESUMO

Altered immune and/or inflammatory response plays an important role in cases of recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). Exacerbation of the maternal immune response through increased NK cell activity and inflammatory cytokines can cause embryo rejection leading to abortion or embryo implantation failure. Immunosuppressors or immunomodulators can help or prevent this condition. Currently, lipid emulsion therapy (LET) has emerged as a treatment for RPL and RIF in women with abnormal NK cell activity, by decreasing the exacerbated immune response of the maternal uterus and providing a more receptive environment for the embryo. However, the mechanisms by which the intralipid acts to reduce NK cell activity are still unclear. In this review, we focus on the studies that conducted LET to treat patients with RPL and RIF with abnormal NK cell activity. We find that although some authors recommend LET as an effective intervention, more studies are necessary to confirm its effectiveness in restoring NK cell activity to normal levels and to comprehend the underlying mechanisms of the lipids action in ameliorating the maternal environment and improving the pregnancy rate.

Assuntos

RESUMO

Background and objectives: Thyroid autoimmunity (TAI) has been associated with a significantly increased risk of miscarriage in women with recurrent pregnancy loss (RPL). The aim of this study was to determine the prevalence of TAI in women with RPL and compare the clinical characteristics of positive and negative TAI women. Materials and Methods: This is a retrospective cross-sectional study; 203 women with RPL were included. Thyroid profile, anti-thyroid peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies were measured in all participants. Clinical characteristics and causes of RPL were compared between positive and negative TAI. Results: Prevalence of TAI was 14.8%; prevalence of positive TPO-Ab and TG-Ab was 12.3% and 4.9%, respectively. Women with TAI had significantly higher concentrations of thyrotropin (TSH) compared to women without TAI (4.8 ± 3.8 versus 3.1 ± 1.1, p = 0.001). There was no significant difference in age, the number of gestations, miscarriages, state of antiphospholipid antibodies (aPL), or causes of RPL between women that were TAI-positive versus TAI-negative. Prevalence of positive TAI by cause of RPL was: endocrine 7/25 (28%), genetic 1/5 (20%), autoimmune 1/5 (20%), anatomic 8/55 (14.5%), and unexplained cause 13/112 (11.6%). Conclusions: The prevalence of TAI in women with RPL is 14.8%. Women with an endocrine cause have the highest prevalence of TAI.

Assuntos

RESUMO

Recurrent pregnancy loss (RPL) affects up to 5% of couples. It is believed that genetic factors contribute to the disease's etiology and pathophysiology. Hundreds of genes represent coherent RPL candidates due to mammalian implantation's inherent complexity. Sanger sequencing (direct sequencing) of candidate genes has identified potential RPL causative genes (and variants), including those regulating embryo implantation and pregnancy maintenance. Although this approach is a reliable technique, the simultaneous analysis of large genomic regions is challenging. Next-generation sequencing (NGS) technology has thus emerged as a useful alternative for determining genetic variants and transcriptomic disturbances contributing to monogenic and polygenic diseases pathogenesis. However, interpreting results remains challenging as NGS experiments provide an enormous amount of complex data. The molecular aspects of specific diseases must be fully understood for accurate interpretation of NGS data. This review was thus aimed at describing (for the first time) the most relevant studies involving Sanger and NGS sequencing, leading to the description of variants related to RPL pathogenesis. Successful RPL-related NGS initiatives (including RNAseq-based studies) and future challenges are discussed. We consider that the information given here should be useful for clinicians, scientists, and students to enable a better understanding of RPL etiology. It may also provide a basis for the development of diagnostic/prognostic approaches contributing toward translational medicine.

Assuntos

RESUMO

Objective: To evaluate the difference between chromosomal abnormalities between the gender of couples affected by Recurrent miscarriage (RM) and if there is an association between previous obstetric history and chromosomal abnormalities of the parents.Methods: Multicenter, retrospective, observational study from seven different RM clinics between 2006 and 2016. We enrolled 707 couples (1014 participants) with a history of RM. We compared the frequency of chromosomal abnormalities between groups of couples with primary and secondary RM and separated between women and their partners. Furthermore, we compared the prevalence of chromosomal abnormalities between groups based on the number of previous spontaneous abortions.Results: The overall prevalence of all cytogenetic abnormalities was 5.59% (n = 1414, women and their partners). Excluding cases of polymorphism and inversion of chromosome 9, which are considered variants of normality, the prevalence in all individuals was 2.26% (n = 32/1414). The comparative analysis of cases of chromosomal abnormalities among couples with primary and secondary RM based on the number of previous miscarriages (PM) revealed a similar frequency between groups. The statistical analysis of the total cases (primary PM + secondary PM) in these three groups were as follows: (a) couple, 2 pm versus 3 pm vs. ≥4 PM, p = .514; (b) women, 2 pm versus 3 pm vs. ≥4 PM, p = .347; and (3) partner, 2 pm versus 3 pm vs. ≥4 PM, p = .959. Chromosomal abnormalities were significantly more prevalent among women than among their partners (6.9 versus 4.2%; p = .027). Moreover, the distribution of leading chromosomal abnormalities among women was different compared with their partners. Among women, we observed these abnormalities in the following frequency order: mosaicism (38.8%), polymorphism (32.6%), translocation (16.3%), and inversion (12.3%). Among their partners, these abnormalities were polymorphism (73.3%), inversion (13.3%), mosaicism (6.7%), and translocation (6.7%).Conclusion: The number of PM and the history of full-term pregnancy does not correlate with an increase or decrease in the prevalence of cytogenetic abnormalities in couples with RM.

Assuntos

RESUMO

BACKGROUND: Human reproductive disorders consist of frequently occurring dysfunctions including a broad range of phenotypes affecting fertility and women's health during pregnancy. Several female-related diseases have been associated with hypofertility/infertility phenotypes, such as recurrent pregnancy loss (RPL). Other occurring diseases may be life-threatening for the mother and foetus, such as preeclampsia (PE) and intra-uterine growth restriction (IUGR). FOXD1 was defined as a major molecule involved in embryo implantation in mice and humans by regulating endometrial/placental genes. FOXD1 mutations in human species have been functionally linked to RPL's origin. METHODS: FOXD1 gene mutation screening, in 158 patients affected by PE, IUGR, RPL and repeated implantation failure (RIF), by direct sequencing and bioinformatics analysis. Plasmid constructs including FOXD1 mutations were used to perform in vitro gene reporter assays. RESULTS: Nine non-synonymous sequence variants were identified. Functional experiments revealed that p.His267Tyr and p.Arg57del led to disturbances of promoter transcriptional activity (C3 and PlGF genes). The FOXD1 p.Ala356Gly and p.Ile364Met deleterious mutations (previously found in RPL patients) have been identified in the present work in women suffering PE and IUGR. CONCLUSIONS: Our results argue in favour of FOXD1 mutations' central role in RPL, RIF, IUGR and PE pathogenesis via C3 and PlGF regulation and they describe, for the first time, a functional link between FOXD1 and implantation/placental diseases. FOXD1 could therefore be used in clinical environments as a molecular biomarker for these diseases in the near future.

Assuntos

RESUMO

Excessive oxidation and antioxidant imbalance resulting from several conditions may cause sperm DNA damage, which, in turn, affect male fertility, both natural and assisted. Sperm DNA damage transferred to the embryo might also affect the health of offspring. Several conditions associated with excessive oxidative stress are modifiable by the use of specific treatments, lifestyle changes, and averting exposure to environmental/occupational toxicants. Here, we discuss the strategies to reduce sperm DNA damage with a focus on clinical and surgical interventions.

Assuntos

RESUMO

PURPOSE: Idiopathic recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder where an impaired control of apoptosis is likely involved. Triggering the cell death mechanism occurs in a spatiotemporal manner and is strongly related to a healthy pregnancy. Single nucleotide polymorphisms (SNPs) at the regulatory regions of genes are known to influence the expression patterns of apoptosis-related molecules. METHODS: A total of 296 unrelated female Brazilian patients were evaluated for clinical-demographic variables and genetic factors: 140 women who had experienced an unexplained RPL (with at least two consecutive abortions) and 156 healthy multiparous women. In all patients, six SNPs were evaluated in genes of apoptosis-related pathways: FAS (rs2234767, rs1800682), FAS-L (rs763110, rs5030772), BAX (rs4645878), and BCL-2 (rs2279115) by PCR followed by a restriction fragment length polymorphism (RFLP)-based analysis. RESULTS: The BAX-248GA genotype is independently associated with idiopathic RPL [adjusted OR = 0.30, 95% CI 0.13-0.70, P = 0.005] susceptibility. In the same multivariate model, the variables ethnicity, smoking, and alcohol consumption were statistically associated with RPL susceptibility (P < 0.05). No association with RPL susceptibility was reported for the remaining SNPs. CONCLUSION: Our study is the first to evaluate the role of the main SNPs from both the extrinsic and intrinsic apoptosis pathways in RPL susceptibility. The association of BAX-248G/A with RPL susceptibility suggests that maternal predisposition for RPL has an essential contribution from genes involved in the delicate balance of endometrium cell turnover (cell death/proliferation). Therefore, apoptotic genes may represent promising targets for future studies on healthy pregnancies and the spectrum of pregnancy disorders.

Assuntos

RESUMO

Recurrent pregnancy loss (RPL) affects up to 5% of couples. It is believed that genetic factors contribute to the disease's etiology and pathophysiology. Hundreds of genes represent coherent RPL candidates due to mammalian implantation's inherent complexity. Sanger sequencing (direct sequencing) of candidate genes has identified potential RPL causative genes (and variants), including those regulating embryo implantation and pregnancy maintenance. Although this approach is a reliable technique, the simultaneous analysis of large genomic regions is challenging. Next-generation sequencing (NGS) technology has thus emerged as a useful alternative for determining genetic variants and transcriptomic disturbances contributing to monogenic and polygenic diseases pathogenesis. However, interpreting results remains challenging as NGS experiments provide an enormous amount of complex data. The molecular aspects of specific diseases must be fully understood for accurate interpretation of NGS data. This review was thus aimed at describing (for the first time) the most relevant studies involving Sanger and NGS sequencing, leading to the description of variants related to RPL pathogenesis. Successful RPL-related NGS initiatives (including RNAseq-based studies) and future challenges are discussed. We consider that the information given here should be useful for clinicians, scientists, and students to enable a better understanding of RPL etiology. It may also provide a basis for the development of diagnostic/prognostic approaches contributing toward translational medicine.

RESUMO

BACKGROUND AND OBJECTIVES: Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, -675 4G/5G PAI-1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies. PATIENTS AND METHODS: We performed a case-control study that included 247 patients with idiopathic RPL (cases), 107 fertile controls and 224 subjects from general population (reference group). Cases were stratified according to the gestational time of the losses (early RPL, n = 89; late losses, n = 158; foetal losses, n = 107) and according to the type of vascular obstetric pathologies. RESULTS: No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (p >.05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (p >.05), except for the factor V Leiden carriage in patients with foetal growth retardation vs. controls (11.8%, 4/34 vs. 1.9%, 2/107; p = .04) (OR = 7.11 [1.24-40.93], p = .03). CONCLUSIONS: Factor V Leiden might have a significant impact on certain obstetric pathologies such as foetal growth retardation. The genetic variants, 10034C/T gamma fibrinogen and 7872C/T factor XI, associated with thromboembolic disease, would not have an impact on PRE.

Assuntos

RESUMO

Transcription factors (TFs) participate in a wide range of cellular processes due to their inherent function as essential regulatory proteins. Their dysfunction has been linked to numerous human diseases. The forkhead box (FOX) family of TFs belongs to the "winged helix" superfamily, consisting of proteins sharing a related winged helix-turn-helix DNA-binding motif. FOX genes have been extensively present during vertebrates and invertebrates' evolution, participating in numerous molecular cascades and biological functions, such as embryonic development and organogenesis, cell cycle regulation, metabolism control, stem cell niche maintenance, signal transduction, and many others. FOXD1, a forkhead TF, has been related to different key biological processes such as kidney and retina development and embryo implantation. FOXD1 dysfunction has been linked to different pathologies, thereby constituting a diagnostic biomarker and a promising target for future therapies. This paper aims to present, for the first time, a comprehensive review of FOXD1's role in mouse development and human disease. Molecular, structural, and functional aspects of FOXD1 are presented in light of physiological and pathogenic conditions, including its role in human disease aetiology, such as cancer and recurrent pregnancy loss. Taken together, the information given here should enable a better understanding of FOXD1 function for basic science researchers and clinicians.

Assuntos

RESUMO

PURPOSE: Annexin A5 (ANXA5) is a protein abundantly expressed in normal placenta where it contributes to the healthy outcome of a pregnancy. Lower ANXA5 levels have been observed in M2/ANXA5 haplotype carrying chorion. Consequently, this study aimed to assess the potential association of M2 maternal carrier status with the risk of recurrent pregnancy loss (RPL), the timing of miscarriages, and other obstetric complications, for the first time in a population from Latin America. METHODS: This study was designed as a prospective recruitment of RPL patients with post hoc analysis. The distribution of the M2/ANXA5 haplotype was compared between a group of 229 Argentine women with RPL and 100 parous controls, and was further analyzed in subgroups of patients stratified according to the timing of miscarriages and in relation to other obstetric complications. RESULTS: No significant differences were found in the distribution of M2 haplotype among either RPL patients or the subgroups with embryonic, early fetal, or late fetal losses compared to parous controls. Notwithstanding, maternal M2/ANXA5 was found to be independently associated with a higher risk of suffering intrauterine growth restriction (IUGR) and/or preeclampsia (PE). Simultaneously, the presence of inherited and/or acquired thrombophilia also proved to be an independent risk factor for these. CONCLUSIONS: The association found between the maternal carriage of the M2/ANXA5 haplotype and an elevated risk of IUGR and/or PE supports the hypothesis that carrier status of this haplotype and the consequently reduced placental ANXA5 expression might be responsible, at least partially, for the onset of these gestational vascular complications.

Assuntos

RESUMO

Recurrent pregnancy loss (RPL) is a reproductive disorder defined as two or more successive and spontaneous pregnancy losses (before 20 weeks of gestation), which affects approximately 1-2% of couples. At present, the causes of RPL remain unknown in a considerable number of cases, leading to complications in treatment and high levels of stress in couples. Idiopathic recurrent pregnancy loss (iRPL) has become one of the more complicated reproductive problems worldwide due to the lack of information about its etiology, which limits the counseling and treatment of patients. For that reason, iRPL requires further study of novel factors to provide scientific information for determining clinical prevention and targeted strategies. The aim of this study is to describe the most recent and promising progress in the identification of potential genetic and epigenetic risk factors for iRPL, expanding the genetic etiology of the disease.

Assuntos

RESUMO

Objetivos: O aborto de repetição acomete 1% a 2% dos casais. Tendo em vista a relevância do assunto, o presente trabalho tem como objetivo abordar o seu melhor manejo clínico. Para isso, critérios diagnósticos, métodos de investigação e tratamentos, além de uma visão geral sobre suas principais causas foram abordados. Métodos: Os artigos foram pesquisados na base de dados PubMed, em maio de 2018, utilizando os termos descritores miscarriage, recurrent; recurrent miscarriage; recurrent miscarriages; abortion, recurrent; recurrent abortion; recurrent abortions; recurrent pregnancy loss. Como critérios de inclusão, foram considerados artigos publicados nos últimos 5 anos, no período de maio de 2014 a maio de 2018, artigos que abordassem pesquisas apenas com humanos, guidelines e aqueles publicados em língua portuguesa, inglesa ou espanhola. Artigos de revisão foram excluídos da seleção. Resultados: Na pesquisa inicial, utilizando os termos descritores, foram encontrados 4492 artigos; restringindo aos últimos 5 anos, restaram 1429 artigos; desses, foram selecionados apenas aqueles com pesquisas em seres humanos, restaram 1004 artigos e desses selecionamos 962 que estão nos idiomas escolhidos. Os artigos de revisão foram excluídos da seleção. Vinte artigos foram incluídos para a elaboração desta revisão da literatura. Conclusões: Através deste artigo foi possível revisar evidências atuais referentes a diagnóstico e a manejo clínico nos casos de abortamento de repetição. Além de proporcionar conhecimento e orientação a estudantes e profissionais, o artigo levanta questões que ainda não estão bem estabelecidas na prática clínica e que ainda necessitam de maiores estudos.

Objective: The recurrent pregnancy loss affects approximately 1% to 2% of couples. Due to its importance, the present revision aims to approach the best clinical management. To do that, diagnosis criteria, research and treatments methods, as well as the general vision of the main causes, were discussed. Methods: The articles were searched in the PUBmed database, in May 2018, using keywords: miscarriage, recurrent; recurrent miscarriage; recurrent miscarriages; abortion, recurrent; recurrent abortion; recurrent abortions; recurrent pregnancy loss. As inclusion criteria, articles published in the past 5 years were chosen, from May 2014 to May 2018, articles that deal with researches in humans, guidelines and publications in portuguese, spanish or english. Revision articles were excluded. Results: In the initial search, using the terms descriptors, we found 4492 articles; restricting to the last 5 years, 1429 papers were found; selecting only those in humans, there were 1004 articles remaining and of those 962 selected in the chosen languages. Review articles were excluded from the selection. Twenty articles were selected for this review. Conclusions: Through this article it was possible to review current evidence regarding diagnosis and clinical management in recurrent pregnancy loss. In addition to provide knowledge and guidance to students and professionals, the article raises questions that are not well established in clinical practice yet and that still require further study.

Assuntos