Galectins in Early Pregnancy and Pregnancy-Associated Pathologies.
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ABSTRACT:
SUBMITTER: Jovanovic Krivokuca M
PROVIDER: S-EPMC8744741 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionGalectins are master regulators of maternal immune responses and placentation in pregnancy. Galectin-13 (gal-13) and galectin-14 (gal-14) are expressed solely by the placenta and contribute to maternal-fetal immune tolerance by inducing the apoptosis of activated T lymphocytes and the polarization of neutrophils toward an immune-regulatory phenotype.Furthermore, their decreased placental expression is associated with pregnancy complications, such as preeclampsia and miscarriage. Yet, our knowledge of the immunoregulatory role of placental galectins is incomplete.MethodsThis study aimed to investigate the effects of recombinant gal-13 and gal-14 on cell viability, apoptosis, and cytokine production of peripheral blood mononuclear cells (PBMCs) and the signaling pathways involved.ResultsHerein, we show that gal-13 and gal-14 bind to the surface of non-activated PBMCs (monocytes, natural killer cells, B cells, and T cells) and increase their viability while decreasing the rate of their apoptosis without promoting cell proliferation. We also demonstrate that gal-13 and gal-14 induce the production of interleukin (IL)-8, IL-10, and interferon-gamma cytokines in a concentration-dependent manner in PBMCs. The parallel activation of Erk1/2, p38, and NF-ĸB signaling evidenced by kinase phosphorylation in PBMCs suggests the involvement of these pathways in the regulation of the galectin-affected immune cell functions.DiscussionThese findings provide further evidence on how placenta-specific galectins assist in the establishment and maintenance of a proper immune environment during a healthy pregnancy.
| S-EPMC9832025 | biostudies-literature
Project description:Tosyl activated magnetic beads were used for aptamer selection against PAG- 7 and 18 proteins of bovine origin. PAG proteins were immobilized on beads with further addition of biotin tagged aptamer library. The recognition of aptamers with PAG was identified by ST-HRP based approach which was colorimetric in nature. The selected aptamers were sequenced and at the same time several new aptamers were identified. Later M-fold structure and G-quadruplex score of aptamers were analyzed for their selection. Those aptamers having high G value and complex structure were chosen. In dot blot assay, aptamers recognized PAG protein in an animal after 42 days of artificial insemination which later given birth to a healthy calf. Further the cross reactivity with serum of 0th day animal (post AI) or with non pregnant animal serum was minimal. Aptamers have also shown interaction with PAG protein of buffalo origin. These selected aptamers have commercial application especially in development of biosensors for early detection of pregnancy in bovine.
| S-EPMC8636505 | biostudies-literature
Project description:ObjectiveThis study was conducted to assess the level of pregnancy-associated glycoprotein (PAG) in whole and skim milk samples, and its suitability for early pregnancy diagnosis in goats.MethodsA two-step sandwich enzyme-linked immunosorbent assay (ELISA) system for estimation of milk PAG was developed and validated, which employed caprine-PAG specific polyclonal antisera. Whole and skim milk samples (n = 210 each) from fifteen multiparous goats were collected on alternate days from d 10 to d 30, and thereafter weekly till d 51 postmating. PAG levels in milk samples were estimated by ELISA and the pregnancies were confirmed at d40 post-mating by transrectal ultrasonography (TRUS).ResultsThe level of PAG in whole and skim milk samples of both pregnant and nonpregnant goats remained below the threshold values until d 24 after mating. Thereafter, PAG concentration in whole and skim milk increased steadily in pregnant goats, whereas it continued below the threshold in non-pregnant does. The PAG profiles in whole and skim milk of pregnant goats were almost similar and exhibited strong positive relationship (r = 0.891; p<0.001). Day 26 post-mating was identified as the first time-point for significantly (p<0.05) higher milk PAG concentration in pregnant goats than to non-pregnant goats. When compared to TRUS examination for pregnancy diagnosis, the accuracy and specificity of PAG ELISA using whole and skim milk samples were 94.5% and 95.4%; and 95.3% and 100%, respectively. The high values of area-under-curve (0.904 [whole milk] and 0.922 [skim milk]), demonstrate outstanding discrimination ability of the milk assays. Among the sampling dates chosen, d 37 post-mating was identified as the best suitable time point for collection of milk samples to detect pregnancy in goats.ConclusionThe PAG concentration in whole and skim milk of goats collected between days 26 and 51 post-breeding can be used for the accurate prediction of pregnancy and may be useful for assisting management decisions in goat flocks.
| S-EPMC7888492 | biostudies-literature
Project description:BackgroundMany couples experience difficulties to become pregnant or carry a pregnancy to term due to unknown causes. Here we define pre-pregnancy complications as having prior recurrent pregnancy loss, prior late miscarriages, time to pregnancy more than one year, or the use of artificial reproductive technologies. We aim to identify factors associated with pre-pregnancy complications and poor well-being in early pregnancy.MethodsOnline questionnaire data from 5330 unique pregnancies in Sweden were collected from November 2017 - February 2021. Multivariable logistic regression modelling was used to investigate potential risk factors for pre-pregnancy complications and differences in early pregnancy symptoms.ResultsPre-pregnancy complications were identified in 1142 participants (21%). Risk factors included diagnosed endometriosis, thyroid medication, opioids and other strong pain medication, body mass index > 25 kg/m2 and age over 35 years. Different subgroups of pre-pregnancy complications had unique risk factors. The groups also experienced different pregnancy symptoms in early pregnancy, where women that had experienced recurrent pregnancy loss were at higher risk of depression in their current pregnancy.ConclusionWe report one of the largest pregnancy cohorts with high frequency of pre-pregnancy complications compared to the Swedish population. Prescribed drug use and body weight were the top potentially modifiable risk factors in all groups. Participants that experienced pre-pregnancy complications also had higher risk of depression and pregnancy problems in early pregnancy.
| S-EPMC9993650 | biostudies-literature
Project description:Low fertility remains a leading cause of poor productivity in dairy cattle. In this context, there is significant interest in developing novel tools for accurate early diagnosis of pregnancy. MicroRNAs (miRNAs) are short RNA molecules which are critically involved in regulating gene expression during both health and disease. MiRNAs have been shown to regulate ovarian function, uterine receptivity, embryonic development and placental function. Circulating miRNAs can provide useful biomarkers of tissue function and disease; importantly, differential miRNA profiles have been linked to pregnancy and preeclampsia in humans. This study sought to establish the potential of circulating miRNAs as biomarkers of early pregnancy in cattle. We applied Illumina small-RNA sequencing to profile miRNAs in plasma samples collected from eight non-pregnant heifers on Days 0, 8 and 16 of the oestrous cycle and 11 heifers on Days 16 and 24 of pregnancy. We sequenced a total of 46 samples and generated 9.2 million miRNA reads per sample. There were no differences in miRNA read abundance between any of the pregnant and non-pregnant time-points (FDRâ>â0.1). As a complementary approach, we analysed sample pools (3-4 samples/pool) corresponding to Days 0, 8 and 16 of the oestrous cycle and Day 24 of pregnancy (nâ=â3 pools/group) using Qiagen PCR arrays. A total of 16 miRNAs were differentially expressed (FDRâ<â0.1) in plasma between pregnant and non-pregnant animals. RT-qPCR validation using the same plasma samples confirmed that miR-26a was differentially upregulated on Day 16 pregnant relative to non-pregnant heifers (1.7-fold; Pâ=â0.043), whereas miR-1249 tended to be upregulated in Day 16 pregnant heifers (1.6-fold; Pâ=â0.081). Further validation in an independent group of heifers confirmed an increase in plasma miR-26a levels during early pregnancy, which was significant only on Day 24 (2.0-fold; Pâ=â0.027). Through genome-wide analyses we have successfully profiled plasma miRNA populations associated with early pregnancy in cattle. We have identified miR-26a as a potential circulating biomarker of early pregnancy. Sequencing of three sequencial samples from each of eight cycling animals (Days 0, 8 and 16, total 24 samples) and two samples from each of 11 pregnant animals (Days 16 and 24, total 22 samples). Main comparisons were between non-pregnant and pregnant groups
2016-08-03 | E-GEOD-85090 | biostudies-arrayexpress
Project description:Low fertility remains a leading cause of poor productivity in dairy cattle. In this context, there is significant interest in developing novel tools for accurate early diagnosis of pregnancy. MicroRNAs (miRNAs) are short RNA molecules which are critically involved in regulating gene expression during both health and disease. MiRNAs have been shown to regulate ovarian function, uterine receptivity, embryonic development and placental function. Circulating miRNAs can provide useful biomarkers of tissue function and disease; importantly, differential miRNA profiles have been linked to pregnancy and preeclampsia in humans. This study sought to establish the potential of circulating miRNAs as biomarkers of early pregnancy in cattle. We applied Illumina small-RNA sequencing to profile miRNAs in plasma samples collected from eight non-pregnant heifers on Days 0, 8 and 16 of the oestrous cycle and 11 heifers on Days 16 and 24 of pregnancy. We sequenced a total of 46 samples and generated 9.2 million miRNA reads per sample. There were no differences in miRNA read abundance between any of the pregnant and non-pregnant time-points (FDR > 0.1). As a complementary approach, we analysed sample pools (3-4 samples/pool) corresponding to Days 0, 8 and 16 of the oestrous cycle and Day 24 of pregnancy (n = 3 pools/group) using Qiagen PCR arrays. A total of 16 miRNAs were differentially expressed (FDR < 0.1) in plasma between pregnant and non-pregnant animals. RT-qPCR validation using the same plasma samples confirmed that miR-26a was differentially upregulated on Day 16 pregnant relative to non-pregnant heifers (1.7-fold; P = 0.043), whereas miR-1249 tended to be upregulated in Day 16 pregnant heifers (1.6-fold; P = 0.081). Further validation in an independent group of heifers confirmed an increase in plasma miR-26a levels during early pregnancy, which was significant only on Day 24 (2.0-fold; P = 0.027). Through genome-wide analyses we have successfully profiled plasma miRNA populations associated with early pregnancy in cattle. We have identified miR-26a as a potential circulating biomarker of early pregnancy.
2016-08-03 | GSE85090 | GEO
Project description:Microglia are brain-resident macrophages that contribute to central nervous system development, maturation, and preservation. Here, we examine the consequences of lifelong absence of microglia on ageing using the Csf1rΔFIRE/ΔFIRE mouse model. In juvenile Csf1rΔFIRE/ΔFIRE mice, we show that microglia are largely dispensable for the transcriptomic maturation of other brain cell types. In contrast, with advancing age, multiple pathologies accumulate in Csf1rΔFIRE/ΔFIRE brains, astrocytes and oligodendrocyte-lineage cells become increasingly dysregulated, and white matter integrity declines, mimicking many of the pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly sensitive to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular disturbances, macroglial dysregulation, and severe calcifications all detected in this region. Thalamic calcification formation, which often occurs with normal ageing, is dramatically accelerated in Csf1rΔFIRE/ΔFIRE brains but can be prevented via transplantation of wild-type microglia. Our results indicate that lifelong absence of microglia results in an age-related neurodegenerative condition that can be prevented by the transplantation of healthy microglia.
2024-05-22 | GSE267545 | GEO
Project description:Limited evidence revealed conflicting results on relationship between phthalate exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort study in Chinese pregnant women (n = 3220) was conducted to investigate the association between urinary phthalate metabolites and clinical pregnancy loss (gestational weeks 6 to 27; n = 109). Morning urine samples during gestational weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The concentrations of low- and high-molecular weight phthalate metabolites (ΣLMWP <250 Da and ΣHMWP >250 Da) were calculated. Adjusted logistic regression models showed increased risks of clinical pregnancy loss in women with higher creatinine- normalized concentrations of MEP, MBP, MEOHP, MEHHP, ΣLMWP and ΣHMWP. Stratified analysis by gestational weeks (10 weeks) of miscarriage indicated positive associations of MEP, MEOHP, MEHHP and ΣHMWP with embryonic loss (during gestational weeks 6 to 10). The only association of foetal loss (during gestational weeks 11 to 27) was observed with MEHHP. Our findings suggested that Chinese women who were exposed to phthalates during early pregnancy had an increased risk of clinical pregnancy loss, especially embryonic loss.
| S-EPMC5533765 | biostudies-literature
Project description:Plasma level of microbial translocation is a marker of mucosal permeability. Increased mucosal permeability ignites elevated microbial translocation and as a consequence of systemic inflammation. Pregnant women with depression have higher levels of inflammatory markers relative to pregnant women without depression, however, no studies have reported whether systemic microbial translocation will change in depressed women during pregnancy. In this study, we examined the plasma LPS level of depressed women during pregnancy. The results showed that the plasma LPS level was significantly increased in depressed mothers during their 8-12 weeks gestation compared to healthy controls. Compared to 8-12 weeks gestation, the plasma LPS levels were significantly decreased at 24-28 weeks gestation and 6-8 weeks postpartum in both depressed subjects and healthy controls. Furthermore, the plasma levels of pro-inflammatory cytokines (TNF-? and MCP/CCL2) associated with microbial translocation were significantly increased in depressed subjects during 8-12 weeks gestation compared to healthy controls. These results indicate that the level of microbial translocation is increased in depressed women during early pregnancy.
| S-EPMC5742552 | biostudies-literature
Project description:BackgroundAllostatic load (AL) measures the cumulative impact of chronic stress and is associated with adverse health outcomes. A novel scoring system has previously been developed for AL in early pregnancy that is associated with pre-eclampsia. It was hypothesized that AL, as identified by the present model, is associated with psychosocial stressors and, specifically, poor sleep quality.MethodsWomen were selected from a low-risk, community-dwelling study population who enrolled at <15 weeks gestation. Nine physiologic components were divided among the domains of cardiovascular, metabolic, and inflammatory function. Spearman's rank correlations were used to examine the association of AL with age, income, the Revised Prenatal Distress Questionnaire (NuPDQ), Inventory of Depressive Symptoms (IDS), and Pittsburgh Sleep Quality Index (PSQI). The Wilcoxon rank-sum test was used to compare AL by race and educational attainment.ResultsA total of 103 women were identified, with: a mean age of 29.8 ± 5.0 years, 17.5% black, and mean gestational age 12.2 ± 1.1 weeks. Allostatic load was positively correlated with the PSQI (ρ = 0.23, p = 0.018). There were no associations with age, income, prenatal distress, race, or depression scores. College-educated women had lower AL compared with those with less education (0.57 ± 0.43 vs 0.81 ± 0.55, p = 0.045).ConclusionHigher AL, measured by the pregnancy-specific model, was associated with poorer sleep quality and lower educational attainment, both of which were considered to be chronic stressors. These relationships were consistent with previous findings in non-pregnant populations, and suggest that AL may be useful for capturing the physiologic impact of chronic stress in early pregnancy.
| S-EPMC5501183 | biostudies-literature