scholarly journals Activation of proneuronal transcription factor Ascl1 in maternal liver ensures a healthy pregnancy

2021 ◽  
Author(s):  
Joonyong Lee ◽  
Veronica Garcia ◽  
Shashank M. Nambiar ◽  
Huaizhou Jiang ◽  
Guoli Dai
Keyword(s):  
Transcription Factor ◽  
Neuronal Development ◽  
Adverse Pregnancy Outcome ◽  
Postnatal Growth ◽  
Hepatocyte Proliferation ◽  
Gene Encoding ◽  
Helix Loop Helix ◽  
Healthy Pregnancy ◽  
Maternal Liver ◽  
Adverse Pregnancy

AbstractBackground & AimsMaternal liver exhibits robust adaptations to pregnancy to accommodate the metabolic needs of developing and growing placenta and fetus by largely unknown mechanisms. We found that achaete-scute homolog-like 1 (Ascl1), a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice.MethodsTo investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from mid-gestation until term.ResultsAs a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 exhibited aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and elevated release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta displayed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 exhibited robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments.ConclusionIn summary, we demonstrate that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies reveal Ascl1 as a novel and critical regulator of the physiology of pregnancy.SynopsisHow the maternal liver adapts to pregnancy remains elusive. We found that maternal liver activates the expression of Ascl1, a gene encoding a proneuronal transcription factor, to coordinate the adaptations of maternal organs and the growth of the placenta, enabling a healthy pregnancy and normal postnatal growth of the offspring.Graphical Abstract

AB0105 CHECKPOINT MOLECULES AND PREGNANCY: ENHANCED SPD-L1 PREDICTS FLARE IN RA PREGNANCY AND POSTPARTUM

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1351.1-1352
Author(s):  
A. L. Stefanski ◽  
K. Eriksson ◽  
A. Zbinden ◽  
P. Villiger ◽  
F. Förger
Keyword(s):  
Birth Weight ◽  
Disease Activity ◽  
Pregnancy Outcome ◽  
Preterm Delivery ◽  
Adverse Pregnancy Outcome ◽  
Healthy Controls ◽  
Serum Samples ◽  
Healthy Pregnancy ◽  
Pregnancy And Postpartum ◽  
Adverse Pregnancy

Background:Rheumatoid arthritis (RA) is a female-predominant autoimmune disease that may affect women in childbearing age, making family planning an important issue for their life. There is a need for better understanding the mechanisms modulating RA in pregnancy and develop prognostic marker regarding adverse pregnancy outcome such as reduced birth weight and preterm delivery. As a crucial organ for peripheral tolerance during pregnancy, the placenta is expressing constitutively programmed cell death ligand 1 (PD-L1), major ligand of the inhibitory receptor PD-1 (Zhang et al, 2015). We hypothesize that the PD-1 pathway plays a central inhibitory role in regulating the course of the disease and pregnancy outcome in RA.Objectives:To investigate the relationship between PD-1 pathway, disease activity during pregnancy/postpartum and pregnancy outcome in RA.Methods:We measured soluble PD-1 and PD-L1 levels by ELISA in serum samples of 27 pregnant RA patients and 25 healthy pregnant controls at different time points during pregnancy and postpartum. As for pregnancy controls, we analyzed serum samples from 28 non-pregnant RA patients and 18 non-pregnant healthy controls. The data was analyzed in correlation with disease activity (measured by DAS28-CRP) and pregnancy outcome (defined as preterm delivery and birth weight). Statistics were calculated by Mann-Whitney U test and Wilcoxon test, correlations by Spearman rank test.Results:In healthy pregnancy, sPD-L1 increases significantly in the 1sttrimester (p = 0,0198) and decreases significantly postpartum (p = 0,0029). sPD-L1 values are higher in non-pregnant RA patients compared to non-pregnant healthy controls (p = 0,047) and there are no significant changes during RA pregnancy. Postpartum sPD-L1 values are significantly higher in RA patients compared to healthy controls (p = 0,0014), Fig. 1. Notably, regarding disease activity, we noticed a significant positive correlation between the overall sPD-L1 values in RA and DAS28-CRP (p= 0.0104), Fig. 2. No significant correlation was seen between sPD-L1, birth weight and preterm delivery. For sPD-1 we focused on 3rdtrimester and postpartum, however, there was no difference between healthy controls and RA patients and no correlation with disease activity or pregnancy outcome.Conclusion:In healthy pregnancy, we observed an increase of sPD-L1, which decreases after delivery. This supports the hypothesis, that PD-1 pathway may be involved in shaping the physiological fetal-maternal tolerance. In RA higher sPD-L1 values are measured already in non-pregnant patients compared to healthy controls and there is no physiological decrease postpartum. Intriguing, sPD-L1 correlates positively with RA disease activity, reflecting a possible functional antagonism towards the inhibitory function of membrane bound PD-L1 molecules. However, the detailed function of sPD-L1 need to be further delineated. Nevertheless, sPD-L1 may have the potential to serve as prognostic marker for flares in RA pregnancy. Regarding the rather rarely observed adverse pregnancy outcome, larger cohorts need to be investigated.References:[1]Zhang YH, Tian M, Tang MX et al. Recent Insight into the Role of the PD-1/PD-L1 Pathway in Feto-Maternal Tolerance and Pregnancy. Am J Reprod Immunol. 2015 Sep;74(3):201-8.Disclosure of Interests:Ana-Luisa Stefanski: None declared, Klara Eriksson: None declared, Astrid Zbinden: None declared, Peter Villiger Consultant of: MSD, Abbvie, Roche, Pfizer, Sanofi, Speakers bureau: Roche, MSD, Pfizer, Frauke Förger Grant/research support from: Unrestricted grant from UCB, Consultant of: UCB, GSK, Roche, Speakers bureau: UCB, GSK

scholarly journals Endometrial Decidualization: The Primary Driver of Pregnancy Health

2020 ◽  
Vol 21 (11) ◽  
pp. 4092
Author(s):  
Shu-Wing Ng ◽  
Gabriella A. Norwitz ◽  
Mihaela Pavlicev ◽  
Tamara Tilburgs ◽  
Carlos Simón ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Inflammatory Response ◽  
Immune Tolerance ◽  
Adverse Pregnancy Outcome ◽  
Tissue Invasion ◽  
Healthy Pregnancy ◽  
Expression Of Genes ◽  
Primary Driver ◽  
Adverse Pregnancy

Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst—including the downregulation of genes involved in the pro- inflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion—leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.

Renal disease in pregnancy

2020 ◽  
pp. 170-185
Author(s):  
David Williams
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Pregnancy Outcome ◽  
Chronic Renal Disease ◽  
Adverse Pregnancy Outcome ◽  
Physiological Change ◽  
Healthy Pregnancy ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
In Pregnancy

The kidneys undergo marked physiological changes during healthy pregnancy. Awareness of these gestational changes is critical to the management of kidney disease in pregnancy as they both mask and mimic renal disease. Gestational changes to maternal vasculature, clotting, and metabolism predispose previously healthy women to a unique set of acute kidney injuries during pregnancy, whereas women with chronic kidney disease make suboptimal gestational adaptations to pregnancy, with an increased risk of adverse pregnancy outcome and possible further damage to their kidneys. Women with kidney transplants can be confident about the safety of established immunosuppressive regimens during pregnancy and can expect a good pregnancy outcome dictated by the function of their renal graft. Pregnancy outcomes for women on renal replacement therapy have improved through intensive haemodialysis regimens that mimic gestational physiological change. This chapter describes renal physiological change and the management of acute and chronic renal disease in pregnancy.

scholarly journals The basic helix-loop-helix transcription factors LIN-32 and HLH-2 function together in multiple steps of a C. elegans neuronal sublineage

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5415-5426 ◽  
Author(s):  
D.S. Portman ◽  
S.W. Emmons
Keyword(s):  
Transcription Factors ◽  
Neuronal Development ◽  
Cell Types ◽  
Gene Encoding ◽  
Structural Cell ◽  
C Elegans ◽  
Helix Loop Helix ◽  
Bhlh Genes

bHLH transcription factors function in neuronal development in organisms as diverse as worms and vertebrates. In the C. elegans male tail, a neuronal sublineage clonally gives rise to the three cell types (two neurons and a structural cell) of each sensory ray. We show here that the bHLH genes lin-32 and hlh-2 are necessary for the specification of multiple cell fates within this sublineage, and for the proper elaboration of differentiated cell characteristics. Mutations in lin-32, a member of the atonal family, can cause failures at each of these steps, resulting in the formation of rays that lack fully-differentiated neurons, neurons that lack cognate rays, and ray cells defective in the number and morphology of their processes. Mutations in hlh-2, the gene encoding the C. elegans E/daughterless ortholog, enhance the ray defects caused by lin-32 mutations. In vitro, LIN-32 can heterodimerize with HLH-2 and bind to an E-box-containing probe. Mutations in these genes interfere with this activity in a manner consistent with the degree of ray defects observed in vivo. We propose that LIN-32 and HLH-2 function as a heterodimer to activate different sets of targets, at multiple steps in the ray sublineage. During ray development, lin-32 performs roles of proneural, neuronal precursor, and differentiation genes of other systems.

scholarly journals A Review of the Potential Interaction of Selenium and Iodine on Placental and Child Health

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2678
Author(s):  
Nahal Habibi ◽  
Jessica A. Grieger ◽  
Tina Bianco-Miotto
Keyword(s):  
Oxidative Stress ◽  
Pregnancy Outcomes ◽  
Maternal Nutrition ◽  
Disease Risk ◽  
Adverse Pregnancy Outcome ◽  
Potential Interaction ◽  
Future Health ◽  
Chronic Disease Risk ◽  
Healthy Pregnancy ◽  
Adverse Pregnancy

A healthy pregnancy is important for the growth and development of a baby. An adverse pregnancy outcome is associated with increased chronic disease risk for the mother and offspring. An optimal diet both before and during pregnancy is essential to support the health of the mother and offspring. A key mediator of the effect of maternal nutrition factors on pregnancy outcomes is the placenta. Complicated pregnancies are characterized by increased oxidative stress in the placenta. Selenium and iodine are micronutrients that are involved in oxidative stress in placental cells. To date, there has been no comprehensive review investigating the potential synergistic effect of iodine and selenium in the placenta and how maternal deficiencies may be associated with increased oxidative stress and hence adverse pregnancy outcomes. We undertook a hypothesis-generating review on selenium and iodine, to look at how they may relate to pregnancy complications through oxidative stress. We propose how they may work together to impact pregnancy and placental health and explore how deficiencies in these micronutrients during pregnancy may impact the future health of offspring.

Reproductive health issues in patients with psoriasis (literature review)

2019 ◽  
Vol 1 (7) ◽  
pp. 5-8
Author(s):  
L. S. Kruglova ◽  
A. A. Osina ◽  
A. A. Khotko
Keyword(s):  
Drug Therapy ◽  
Reproductive Health ◽  
Literature Review ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcome ◽  
Certolizumab Pegol ◽  
Genetically Engineered ◽  
Health Issues ◽  
Degree Of Confidence ◽  
Adverse Pregnancy

Among patients with psoriasis, approximately 50% are women and almost 75 % of them are under the age of 40 years. Thus, most women with psoriasis have childbearing potential. When pregnancy occurs in 22 % of patients, the activity of psoriasis persists, characteristic of the course before pregnancy, in 23 % of women, the course of the disease worsens. The article provides up-to-date data on the management of pregnant patients with psoriasis. To improve pregnancy outcomes in patients with psoriasis, it is important to prevent exacerbation of the disease. The choice of drug therapy in this case is based on an assessment of the ratio of the risk of undesirable effects of the drugs on the developing fetus and the risk of the development of exacerbation of psoriasis, which can cause an adverse pregnancy outcome. Despite the fact that the available clinical experience of using genetically engineered drugs is still limited, with a certain degree of confidence we can say that there is no increase in the risk of adverse pregnancy outcomes associated with therapy with certolizumab pegol.

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