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During pregnancy, maternal blood circulates through the intervillous space of the placenta and the reciprocal interactions between foetal tissues and maternal immune cells makes the intervillous space a unique immunological niche. Labour is characterised by a proinflammatory response in the myometrium, but the relationship between local and systemic changes during the onset of labour remains elusive. We here aimed to investigate how the systemic and intervillous circulatory systems are affected during labour from an immunological point of view. We report that the proportion of monocytes is dramatically higher in peripheral (PB), intervillous blood (IVB) and decidua in labouring (n = 14) compared to non-labouring women (n = 15), suggesting that labour leads to both a systemic and local mobilisation of monocytes. Labour was associated with a relative increase of effector memory T cells in the intervillous space compared to the periphery, and MAIT cells and T cells showed an elevated expression of activation markers both in PB and IVB. Intervillous monocytes consisted to a higher degree of CD14+CD16+ intermediate monocytes compared to peripheral monocytes, independently of mode of delivery, and displayed an altered phenotypic expression pattern. A proximity extension assay analysis of 168 proteins revealed that several proteins associated to myeloid cell migration and function, including CCL2 and M-CSF, were upregulated in IVB plasma in labouring women. Thus, the intervillous space could be a bridging site for the communication between the placenta and the periphery, which contribute to monocyte mobilisation and generation of inflammatory reactions during spontaneous labour.
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Trabajo de Parto , Células T Invariantes Asociadas a Mucosa , Embarazo , Femenino , Humanos , Monocitos , Factores Quimiotácticos , PlacentaRESUMEN
Background: Transcription factor 7-like 2 (TCF7L2) gene has a significant role in hyperglycemia in pregnancy (HIP) risk. The current study was planned with the aim to evaluate the association of single nucleotide polymorphism (SNP) rs7903146 in patients of newly detected HIP among Indian population of northern region. Methods: This study was an observational case control study done among newly detected HIP (The World Health Organization (WHO) criteria, 2013) and healthy pregnant females without diabetes. Participants from both the group were genotyped for rs7903146 (C/T) variant of TCF7L2 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: A total of 71 cases of newly detected HIP were included in the study, out of which 25 (35.2%) of them were of first-time detected diabetes mellitus in pregnancy (DIP) and 46 (64.7%) were of gestational diabetes (GDM) and 100 were pregnant females without diabetes in third trimester were enrolled as controls. Average age of participants in the case group was 28.7 ± 4.0 years and the control group were 26.5 ± 3.6 years (P value 0.09). The wild homozygous CC genotype, heterozygous CT genotype and homozygous TT genotype were present in 39.4%, 53.5%, 7.1% of case group vs 53%, 43% and 4% of control group, respectively. No significant association of rs7903146(C/T) SNP of TCF7L2 gene in HIP (CC/CT, CC/TT P value 0.15, 0.38, respectively) in our population was found. There was no significant difference in the distribution of genotypes between DIP and GDM. Conclusion: This study shows no evidence of association of rs7903146(C/T) SNP of TCF7L2 gene with newly detected HIP in our population.
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PROBLEM: Hyperhomocysteinemia (hypHcy) due to impaired folate metabolism is shown to be a risk factor for preterm birth (PTB) and low birth weight (LBW) in mothers. However, the relationship of fetal hypHcy with adverse pregnancy outcomes is under-represented. The present study aims to investigate the association of fetal hypHcy with oxidative stress and placental inflammation that can contribute to an early breakdown of maternal-fetal tolerance in pre-term birth (PTB). METHODS: Cord blood and placenta tissue were collected from PTB and term infant group. Levels of homocysteine, folic acid, vitamin B12 and oxidative stress markers (MDA, T-AOC, 8-OHdG) were measured in cord blood serum using ELISA and respective standard assay kits. Relative expression of candidate genes (TNF-α, IL-6, IL1-ß, VEGF-A, MMP2 and MMP9) was also checked using RT-PCR and immunoblotting/immunohistochemistry. RESULTS: PTB infants showed significantly higher levels of homocysteine (P = .02) and lower levels of vitamin B12 (P = .005) as compared to term infants. We also found that PTB infants with hypHcy had lower T-AOC (P = .003) and higher MDA (P = .04) levels as compared to term infants with normal homocysteine levels. The mRNA and protein levels of TNF-α, VEGF-A, MMP2 and MMP9 were significantly higher in hypHcy PTB infants. CONCLUSION: Our results show that fetal hypHcy is associated with oxidative stress and an increase in inflammatory markers in the placenta. Thus, in conclusion, our study demonstrates that fetal hypHcy during pregnancy is a potential risk factor that may initiate an early breakdown of uterine quiescence due to activation of inflammatory processes leading to PTB.
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Hiperhomocisteinemia , Nacimiento Prematuro , Biomarcadores/metabolismo , Femenino , Sangre Fetal/metabolismo , Ácido Fólico/metabolismo , Homocisteína/metabolismo , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/metabolismo , Lactante , Recién Nacido , Inflamación/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Placenta/metabolismo , Embarazo , Nacimiento Prematuro/metabolismo , Nacimiento a Término , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vitamina B 12/metabolismoRESUMEN
Synergistic interplay of immune endocrine interaction is prerequisite for an effective maternal fetal tolerance. Pre-term birth (PTB) may be a consequence of altered immune-endocrine crosstalk during third trimester resulting in early breakdown of this tolerance. Myeloid derived suppressor cells (MDSCs), a heterogenous population of immature immune cells are increased in pregnant women and healthy newborns, but their role in PTB still remains obscure. We now report that granulocytic MDSCs (G-MDSCs) is decreased in women delivering prematurely, suggesting their potential role in maintaining maternal fetal tolerance. Interestingly, in contrast statistically significant increase in MDSCs and monocytic MDSCs (M-MDSCs) along with positive correlation with cord serum estradiol (E2), and overexpressed ER-α in placental tissue suggested E2 mediated accumulation of M-MDSCs in PTB babies. MDSCs mediated immune suppression is accompanied with subsequent decline in total T cells and its subtypes: Th and Tc in PTB babies, which signifies their potential contribution towards the impaired immune system of PTB babies.
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Estradiol/sangre , Recien Nacido Prematuro/inmunología , Células Supresoras de Origen Mieloide/inmunología , Nacimiento Prematuro/inmunología , Adulto , Estudios de Casos y Controles , Receptor alfa de Estrógeno/análisis , Receptor alfa de Estrógeno/metabolismo , Femenino , Sangre Fetal , Histocompatibilidad Materno-Fetal , Humanos , Inmunofenotipificación , Recién Nacido , Edad Materna , Placenta/patología , Embarazo , Nacimiento Prematuro/sangre , Nacimiento Prematuro/patología , Factor de Transcripción STAT3/análisis , Factor de Transcripción STAT3/metabolismoRESUMEN
We investigated the impact of socio-demographic variables on antenatal care (ANC) utilization and the low birth weight of a child. Data were collected from 300 pregnant females. Only 22.5% of females received full antenatal care (≥4 visits). Our results showed that female's age at marriage and education plays a significant role in improving ANC. We observed an overall decrease in the utilization of services provided during each antenatal visit. ANC visits from the first trimester decrease the risk of having a baby with low birth weight. Awareness programs and educating families about pregnancy care are recommended to improve ANC utilization.
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Aceptación de la Atención de Salud , Atención Prenatal , Niño , Femenino , Humanos , India , Matrimonio , Embarazo , Mujeres EmbarazadasRESUMEN
PROBLEM: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth. METHOD OF STUDY: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study. RESULTS: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies. CONCLUSION: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth.
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Sangre Fetal/química , Recien Nacido Prematuro/sangre , Inflamación/sangre , Enfermedades Placentarias/sangre , Nacimiento Prematuro/sangre , Vitamina D/análogos & derivados , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/biosíntesis , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Adulto , Peso al Nacer , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Femenino , Edad Gestacional , Humanos , Lactante , Inflamación/patología , Mediadores de Inflamación/análisis , Enfermedades Placentarias/patología , Embarazo , Complicaciones del Embarazo/sangre , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptores de Calcitriol/biosíntesis , Receptores de Calcitriol/genética , Factor de Transcripción ReIA/sangre , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
PROBLEM: Decline in myeloid-derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation. METHOD OF STUDY: Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G-MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor -α (ER-α), STAT-3/pSTAT-3, and caspase-3, respectively. RESULTS: Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G-MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER- α and increased caspase-3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT-3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT-3 indicates that these processes pertaining to MDSCs are compromised. CONCLUSION: Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal-fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy.
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Aborto Espontáneo/inmunología , Decidua/fisiología , Estradiol/metabolismo , Células Supresoras de Origen Mieloide/fisiología , Progesterona/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Células Cultivadas , Citocinas/metabolismo , Femenino , Humanos , Embarazo , Balance Th1 - Th2 , Tolerancia al Trasplante , Adulto JovenRESUMEN
In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their "Yin and Yang" nature in a more comprehensive and coherent manner.
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Enfermedades Autoinmunes/inmunología , Diabetes Mellitus/inmunología , Células Supresoras de Origen Mieloide/inmunología , Neoplasias/inmunología , Obesidad/inmunología , Animales , Enfermedades Autoinmunes/patología , Diabetes Mellitus/patología , Femenino , Humanos , Masculino , Células Supresoras de Origen Mieloide/patología , Neoplasias/patología , Obesidad/patología , EmbarazoRESUMEN
S100 proteins are calcium (Ca2+)-binding proteins and these have an important function in progression, manifestation and therapeutic aspects of various inflammatory, metabolic and neurodegenerative disorders. Based on their involvement in intracellular or extracellular regulatory effects, S100 proteins are classified into three subgroups: one subgroup is specialized in exerting only intracellular effects, other performs both intracellular and extracellular functions and the third subgroup members only display extracellular regulatory effects. S100 proteins are expressed particularly in vertebrates and have cell-specific expression. Functionally, S100 proteins act through their surface receptors and regulate cell functions in autocrine or paracrine mode. Receptor for advanced glycation end products (RAGEs) and toll-like receptor 4 are the main surface receptors. S100 proteins participate in the regulation of cellular differentiation, proliferation, apoptosis and inflammation along with Ca2+ homeostasis, energy metabolism and cellular migration, and perform the respective functions through their interaction with transcription factors, nucleic acids, enzymes, receptors, cytoskeleton system, etc. Currently, their role in adverse pregnancy outcomes and compromised reproductive health is being explored. These proteins are present in amniotic fluid, endometrium tissue and foetal brain; therefore, it is quite likely that alterations in the expression levels of S100 family members will be affecting the particular function they are involved in and ultimately affecting the pregnancy in adverse manner. The current review discusses about an association of S100 proteins in pregnancy disorders such as endometriosis, intrauterine growth retardation and miscarriage.
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Endometriosis/genética , Inflamación/genética , Reproducción/genética , Proteínas S100/genética , Calcio/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , Endometriosis/patología , Femenino , Homeostasis , Humanos , Inflamación/metabolismo , Embarazo , Resultado del Embarazo , Receptor para Productos Finales de Glicación Avanzada/genética , Proteínas S100/metabolismo , Receptor Toll-Like 4/genéticaRESUMEN
Fertilization is a hallmark event of sexual reproduction marked by the fusion of male and female gamete to form zygote. It is a highly complex, yet a robust process that is intricately regulated by various signalling molecules. A healthy fertilization is determined by the quality of zygote which is contingent on the health of egg and sperm. The relationship between infertility and gametic health can be reciprocal. On one hand gametogenesis has to be dynamic and unremitting to sustain the reproductive health, while on the other hand it has to be error free for proper embryonic development. Complex cellular interactions make gametogenesis highly vulnerable to extrinsic as well as intrinsic intrusions. Molecular disparities during these phases may result in complete fertilization failure. Present review provides an overview of the regulation of gametogenesis, determinants of healthy gamete, players at fertilization window and what may go wrong during the development of zygote to embryo leading to implantation failure. We have outlined different 'windows' of vulnerability during gametogenesis supported by evidences affecting the fertility potential of both the partners.