Is HLA-E a possible genetic marker relevant for natural conception?

BACKGROUND: HLA-E products, class Ib human leukocyte antigens, act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy. AIMS: To evaluate HLA-E role in the establishment of a viable pregnancy. MATERIALS & METHODS: HLA-E was genotyped by sequence-based typing (SBT) and analyzed for specific polymorphisms, comparing couples who underwent assisted reproduction treatment (ART) and fertile control couples. RESULTS: There was a significant difference in HLA-E allele and genotype distributions between ART couples and control couples. The allele HLA-E*01:03 was observed in 63.2% of ART men and in 35.1% of fertile men (P = 0.0032). CONCLUSION: These results suggest that HLA-E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.

HLA-G profile of infertile couples who underwent assisted reproduction treatment.

HLA-G codes for a non-classical class I (Ib) protein which is mainly expressed in trophoblast cells. Many pieces of evidence pointed out its essential role conferring immunological tolerance to the fetus. Some HLA-G alleles have been linked to enhanced or reduced HLA-G protein levels expression, which have been associated with reproductive failure. In this study 33 couples undergoing ART (assisted reproduction treatment; n=66) and 120 couples who conceived naturally (controls; n=240) were enrolled in the study. Genotyping was performed by SBT and tagged an 1837bp at 5'URR as well as exons 2, 3 and4 of HLA-G. Alleles, genotypes and haplotypes were compared between infertile and control groups using Fisher Exact Test. The haplotype HLA-G∗010101b/HLA-G∗01:01:01 showed statistically significant higher frequency in control groups. The immunogenetics of infertility is complex and might be dependent on different genes involved in the establishment of a successful pregnancy. A better understanding of HLA-G alleles and haplotypes structure and how the genetic diversity at their regulatory sites could impact on their level of expression and build up the susceptibility or protection conditions may shed light on the comprehension of immunogenetics mechanisms acting at the fetus-maternal interface.

HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment.

The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART.

HLA-G e reprodução humana / HLA-G and human reproduction

O gene HLA-G tem sido investigado em várias condições clínicas relacionadas à reprodução. Casais com abortamento espontâneo de repetição, mulheres com pré-eclâmpsia ou que se submetem a tratamentos de reprodução assistida têm participado de estudos caso-controle com o objetivo principal de obter informações que possam esclarecer a participação de HLA-G nessas ocorrências clínicas. Este trabalho traz uma revisão bibliográfica com os estudos principais e mais recentes que descrevem o gene HLA-G e suas isoformas proteicas, bem como a variação genética e polimorfismos que possam influenciar etapas importantes do processo reprodutivo humano. Considerando-se a gestação como uma característica multifatorial, com influência de fatores genéticos e ambientais, não existe um consenso sobre o papel desempenhado pelo gene HLA-G nesse processo. No entanto, variantes alélicas de HLA-G e suas correspondentes isoformas solúveis ou de membrana, têm sido associadas a níveis plasmáticos dos HLA-G e consideradas prognóstico favorável do processo implantacional.

The HLA-G has been investigated in several clinic conditions related to reproduction. Couples with spontaneous recurrent miscarriage, women with preeclampsia or who were submitted assisted reproduction treatments have participated in case-control studies whose main objective was to obtain information that could shed light on the involvement of HLA-G in such clinic conditions. This paper presents a bibliographic revision with the most recent major studies describing HLA-G gene and its protein isoforms, genetic variation and polymorphisms that may influence important stages of the human reproductive process. Considering pregnancy as a multifactorial feature, with the influence of genetic and environmental factors, there is no consensus about the role of HLA-G gene in pregnancy. However, allelic variants of HLA-G and their corresponding soluble or membrane bound isoforms, have been associated with plasma levels sHLA-G and considered a favorable prognosis of the implantation process.

Induction and removal of DNA damage in blood leukocytes of patients with type 2 diabetes mellitus undergoing hemodialysis.

Type 2 diabetes mellitus (T2DM) is associated with a high production of reactive oxygen species, which may cause oxidative DNA damage. High levels of genomic damage have been associated with renal failure and hemodialysis. However, no information is available in the literature concerning the levels of DNA damage in T2DM individuals who are dependent on hemodialysis. This study used the comet assay to assess the levels of DNA damage before, immediately after and 48 h after the hemodialysis session in 25 patients with T2DM and in a group of 20 healthy individuals, selected according to mean age, sex and smoking habit. Our results showed increased levels of DNA damage in hemodialysis-dependent T2DM individuals (12.36+/-8.04) when compared with healthy individuals (7.35+/-7.41) (p=0.014). Damage levels increased immediately after the hemodialysis session (19.76+/-12.40) (p=0.04), which suggests a possible action of pro-oxidative factors related to the therapy, with a genotoxic effect on cells. Results obtained 48 h after hemodialysis (6.44+/-5.99) evidenced damage removal (p=0.001), which may be suggestive of DNA repair.

Teste dos micronúcleos: um biomarcador de dano genotóxico em células descamadas da mucosa bucal / Micronucleus assay: a biomarker of genotoxic damage in exfoliated oral mucosa cells

O objetivo deste trabalho é fazer uma revisão de literatura a respeito do ensaio dos micronúcleos, explicando o seu significado e sua aplicação em células esfoliadas da mucosa bucal. Micronúcleo (MN) é um núcleo acessório, originado a partir de fragmentos de cromossomo ou de cromossomos inteiros que não são incluídos no núcleo principal durante a mitose. MNs surgem por alterações genéticas espontâneas ou são induzidos por agentes genotóxicos. A análise dos micronúcleos tem sido utilizada como uma ferramenta importante de biomonitoramento de populações. Estudos demonstram que consumidores de fumo e álcool, assim como grupos expostos a determinados agentes em função de sua ocupação ou estilo de vida apresentam um elevado número de MNs nas células bucais esfoliadas.

The aim of this study is to summarise the literature on micronucleus assay, explaining its meaning and its application in exfoliated oral mucosal cells. Micronuclei (MN) is an extra nuclei, originated from chromosome fragments or whole chromosomes that are not included in the main nuclei during mitosis. MNs arise from spontaneous genetic damage or are induced by genotoxic agents. MN analysis has been used as an important tool to biomonitore populations exposed to life-style agents. Studies demonstrate that tobacco and alcohol users, as well as occupationally exposed groups present increased number of MNs in exfoliated oral mucosa cells. Despite the fact that the role of MN frequency has not yet been fully understood, the MNs assay is considered to be an effective biomarker of oral squamous cell carcinoma risk factors effects.