IUGR and infections

doi:10.1016/S0378-3782(14)70014-3

Early Human Development

Volume 90, Supplement 1, March 2014, Pages S42-S44

https://doi.org/10.1016/S0378-3782(14)70014-3 Get rights and content

ABSTRACT

Intra-uterine growth retardation (IUGR) is usually defined as impaired growth and development of the fetus and/or its organs during gestation. Infants are defined small for gestational age (SGA), following IUGR, when the birth weight is below the 10th percentile. Pre-natal congenital infections caused by T. gondii, rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and Treponema are associated with, and account for, approximately 5 to 15% of IUGR. On the other hand, SGA preterm infants are at increased risk of post-natal infection compared to their age-matched appropriately grown controls, in particular nosocomial infection, irrespective of the responsible pathogen. One possible mechanism is the retarded development in the immune system which has been described in association with IUGR. Indeed, SGA infants have a disproportionately small thymus and low leukocyte, lymphocyte and macrophage counts. However, immune therapies, including prophylactic intravenous immunoglobulins and GM-CSF have not proven to be effective in reducing the incidence of sepsis, and further research is required.

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Citation Excerpt :
Pregnant women infected with other pathogens such as Plasmodium falciparum or Plasmodium vivax (malaria), zika (ZIKV) and even SARS-COV-2 (COVID-19), as well as other examples including Brucella spp (brucellosis), vaginal infection with bacterial vaginosis (polymicrobial), influenza virus (flu), human immunodeficiency virus (HIV) and Dengue virus (DENV), may also exhibit a higher risk of adverse pregnancy outcomes (Adams Waldorf and McAdams, 2013; Bloise et al., 2021b; Epelboin et al., 2017; Giakoumelou et al., 2016; Wong et al., 2021). These pathogens elicit specific cytokine/chemokine inflammatory responses broadly associated with the induction of miscarriage (Giakoumelou et al., 2016), stillbirths (Blackwell, 2015), preeclampsia (PE) (Harmon et al., 2016; Minassian et al., 2013), intrauterine growth restriction (IUGR) (Longo et al., 2014) and preterm labor (Conti et al., 2015), as well as, negative influences on central nervous, cardiovascular, endocrine and reproductive systems (Ahmadian et al., 2020; Fitzgerald et al., 2020; Izvolskaia et al., 2018; Xia et al., 2019). Infectious pathogens may be sensed by the innate immune system via recognition of pathogen-associated molecular patterns (PAMPs; structure-conserved molecules of pathogens) and damage-associated molecular patterns (DAMPs; endogenously released from infected cells).
P-glycoprotein (P-gp, encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP/ABCG2) are efflux multidrug resistance (MDR) transporters localized at the syncytiotrophoblast barrier of the placenta and protect the conceptus from drug and toxin exposure throughout pregnancy. Infection is an important modulator of MDR expression and function. This review comprehensively examines the effect of infection on the MDR transporters, P-gp and BCRP in the placenta. Infection PAMPs such as bacterial lipopolysaccharide (LPS) and viral polyinosinic–polycytidylic acid (poly I:C) and single-stranded (ss)RNA, as well as infection with Zika virus (ZIKV), Plasmodium berghei ANKA (modeling malaria in pregnancy – MiP) and polymicrobial infection of intrauterine tissues (chorioamnionitis) all modulate placental P-gp and BCRP at the levels of mRNA, protein and or function; with specific responses varying according to gestational age, trophoblast type and species (human vs. mice). Furthermore, we describe the expression and localization profile of Toll-like receptor (TLR) proteins of the innate immune system at the maternal-fetal interface, aiming to better understand how infective agents modulate placental MDR. We also highlight important gaps in the field and propose future research directions. We conclude that alterations in placental MDR expression and function induced by infective agents may not only alter the intrauterine biodistribution of important MDR substrates such as drugs, toxins, hormones, cytokines, chemokines and waste metabolites, but also impact normal placentation and adversely affect pregnancy outcome and maternal/neonatal health.
MAP3K4 promotes fetal and placental growth by controlling the receptor tyrosine kinases IGF1R/IR and Akt signaling pathway
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Citation Excerpt :
We predict that FGR will also occur in Map3k4KI/KI mice in the pure C57BL/6N background. FGR-complicated pregnancies are a major public health concern because of increased perinatal mortality and morbidity and long-term consequences of FGR (2, 8–10). Unfortunately, therapies to prevent or treat FGR remain difficult to identify.
Disruption of fetal growth results in severe consequences to human health, including increased fetal and neonatal morbidity and mortality, as well as potential lifelong health problems. Molecular mechanisms promoting fetal growth represent potential therapeutic strategies to treat and/or prevent fetal growth restriction (FGR). Here, we identify a previously unknown role for the mitogen-activated protein kinase kinase kinase 4 (MAP3K4) in promoting fetal and placental growth. We demonstrate that inactivation of MAP3K4 kinase activity causes FGR due in part to placental insufficiency. Significantly, MAP3K4 kinase–inactive mice display highly penetrant lethality prior to weaning and persistent growth reduction of surviving adults. Additionally, we elucidate molecular mechanisms by which MAP3K4 promotes growth through control of the insulin-like growth factor 1 receptor (IGF1R), insulin receptor (IR), and Akt signaling pathway. Specifically, MAP3K4 kinase inactivation in trophoblast stem (TS) cells results in reduced IGF1R and IR expression and decreased Akt activation. We observe these changes in TS cells also occur in differentiated trophoblasts created through in vitro differentiation of cultured TS cells and in vivo in placental tissues formed by TS cells. Furthermore, we show that MAP3K4 controls this pathway by promoting Igf1r transcript expression in TS cells through activation of CREB-binding protein (CBP). In the MAP3K4 kinase–inactive TS cells, Igf1r transcripts are repressed because of reduced CBP activity and increased histone deacetylase 6 expression and activity. Together, these data demonstrate a critical role for MAP3K4 in promoting fetal and placental growth by controlling the activity of the IGF1R/IR and Akt signaling pathway.
Dietary curcumin supplementation ameliorates placental inflammation in rats with intra-uterine growth retardation by inhibiting the NF-κB signaling pathway
2022, Journal of Nutritional Biochemistry
Citation Excerpt :
Moreover, we also found the trace of curcumin in the serum and liver, demonstrating that the accumulation of curcumin could occur in the other tissues of pregnant animals. IUGR, which refers to the impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is an important reproductive problem in humans and domestic animals [34,35]. Several studies have shown that gestational inflammation leads to fetal IUGR due to placental development and functioning impairment [36,37].
Intra-uterine growth restriction (IUGR) is a serious, commonly occurring reproductive problem in humans. This study aimed to investigate the effects of daily curcumin supplementation during pregnancy on placental inflammation, in a rat model of IUGR. Pregnant rats were divided into three groups based on diet: (1) normal protein (19%) (NP), (2) low protein (8%) (LP), and (3) low protein + 100 mg curcumin/kg bw per day (LPC). The results showed that curcumin accumulation in the serum, placenta and liver. Fetal weight and placental total protein levels were increased in the LPC group compared with those in the LP group. Dietary curcumin supplementation normalized the low protein diet-induced decrease of placental weight, blood sinusoid area, and proliferating cell nuclear antigen (PCNA) protein expression levels. It also reversed the low protein diet-induced increase of serum triglyceride levels and tumor necrosis factor alpha-like (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) concentrations in both the placenta and serum. Additionally, it normalized the enhanced gene expression levels of the pro-inflammatory cytokines in the LP group to that in the NP group. Furthermore, it downregulated the inhibitor of kappa Balpha (IκBα) and nuclear factor kappa Balpha (NF-κB) phosphorylation. In conclusion, daily curcumin supplementation ameliorates placental inflammation in rats with IUGR by inhibiting the NF-κB signaling pathway.
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IUGR and infections

ABSTRACT

J Gynécologie Obstétrique Biol Reprod

Early Hum Dev

Lancet

Intrauterine growth retardation—small events, big consequences

Ital J Pediatr

Predictors of fetal growth in maternal HIV disease

Am J Perinatol

How to use … neonatal TORCH testing

Arch Dis Child Educ Pr Ed

Neonatal outcome in growth-restricted versus appropriately grown preterm infants

Am J Perinatol

Perinatal outcome of monochorionic twins with selective IUGR compared with uncomplicated monochorionic twins

Twin Res Hum Genet Off J Int Soc Twin Stud