Role of the IGF system in trophoblast invasion and pre-eclampsia

Irwin, Juan C.; Suen, Lii-Fang; N, Martina; Mark, Silke; Giudice, Linda C.

doi:10.1093/humrep/14.suppl_2.90

Cited by 153 publications

(98 citation statements)

References 26 publications

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“…By interacting mainly with the IGF1R (Wang & Chard 1999), both IGF1 and IGF2 are mitogenic factors whose uterine expression is regulated Embryo-maternal interaction in the dog by steroidogenic hormones (De Cock et al 2002, Bhatti et al 2007, Dantzer & Swanson 2012. They possess differentiation properties capable of influencing embryonic development, as shown, e.g., in humans and ruminants (Wathes et al 1998, Irwin et al 1999, Kim et al 2008. In addition, in human decidua, for example, IGF1 regulates PRL and arachidonic acid secretion (Handwerger et al 1991), the latter serving as a common precursor for PG synthesis.…”

Section: Discussionmentioning

confidence: 99%

Expression of genes involved in the embryo–maternal interaction in the early-pregnant canine uterus

et al. 2014

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Although there is no acute luteolytic mechanism in the absence of pregnancy in the bitch, a precise and well-timed embryo-maternal interaction seems to be required for the initiation and maintenance of gestation. As only limited information is available about these processes in dogs, in this study, the uterine expression of possible decidualization markers was investigated during the pre-implantation stage (days 10-12) of pregnancy and in the corresponding nonpregnant controls. In addition, the expression of selected genes associated with blastocyst development and/or implantation was investigated in embryos flushed from the uteri of bitches used for this study (unhatched and hatched blastocysts). There was an upregulated expression of prolactin receptor (PRLR) and IGF2 observed pre-implantation. The expression of PRL and of IGF1 was unaffected, and neither was the expression of progesterone-or estrogen receptor b (ESR2). In contrast, (ESR1) levels were elevated during early pregnancy. Prostaglandin (PG)-system revealed upregulated expression of PGE2-synthase and its receptors, PTGER2 and PTGER4, and of the PG-transporter. Elevated levels of AKR1C3 mRNA, but not the protein itself, were noted. Expression of prostaglandin-endoperoxide synthase 2 (PTGS2) remained unaffected. Most of the transcripts were predominantly localized to the uterine epithelial cells, myometrium and, to a lesser extent, to the uterine stroma. PGES (PTGES) mRNA was abundantly expressed in both groups of embryos and appeared higher in the hatched ones. The expression level of IGF2 mRNA appeared higher than that of IGF1 mRNA in hatched embryos. In unhatched embryos IGF1, IGF2, and PTGS2 mRNA levels were below the detection limit.

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Section: Discussionmentioning

confidence: 99%

Expression of genes involved in the embryo–maternal interaction in the early-pregnant canine uterus

et al. 2014

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“…Among these factors are the transforming growth factor-␤s (TGF␤s), insulin-like growth factors (IGFs), and their binding proteins (IGFBPs) (Irving and Lala, 1995;Hamilton et al, 1998;Irwin et al, 1999;Chakraborty et al, 2002;Constancia et al, 2002;Nayak and Giudice, 2003;Carter et al, 2004;Pollheimer and Knofler, 2005). Recent studies indicate that HtrA1 is involved in regulating TGF-␤ signalling (Oka et al, 2004) and the IGF/IGFBP system (Hou et al, 2005); HtrA1 may, therefore, have regulatory roles in modulating these two pathways, which are critical for placental development.…”

Section: Figmentioning

confidence: 99%

“…The IGF/IGFBPs are important mediators during placental development and establishment of pregnancy (Han et al, 1996;Irwin et al, 1999;Constancia et al, 2002;Nayak and Giudice, 2003). It is proposed that trophoblast-derived IGFs and decidualderived IGFBPs provide autocrine/ paracrine enhancement of trophoblast migration and invasion (Han et al, 1996;Hamilton et al, 1998;Nayak and Giudice, 2003).…”

Section: Figmentioning

confidence: 99%

Distinct expression and localization of serine protease HtrA1 in human endometrium and first‐trimester placenta

Nie¹,

Hale²,

Liu³

et al. 2006

Developmental Dynamics

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Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternaltrophoblast interface suggests that HtrA1 may play a role in placental development. Developmental Dynamics 235:3448 -3455, 2006.

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“…PAPP-A first identified in 1974, was later shown to be a protease that cleaves insulin-like growth factor binding protein -4 and -5 (IGFBP-4 and -5) to release free Insulin-like Growth Factors (IGF-1 and IGF-2) [7][8][9], and known to play a critical role in the regulation of fetal and placental growth [10][11][12]. Insulin-like Growth Factors (IGFs) are also thought to have an important role in the autocrine and paracrine control of trophoblast invasion of the decidua [13]. Maternal serum PAPP-A concentrations reflect the placental volume; hence low levels of PAPP-A may be an indicator of impaired placental function and implantation.…”

Section: Introductionmentioning

confidence: 99%

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

Ranganathan¹,

Fresen²,

Sarkar³

2017

Obstet Gynecol Rep

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Objectives: To explore the effects of low levels of first trimester Pregnancy Associated Plasma Protein-A (PAPP-A) on adverse pregnancy outcomes.Design: Single centre retrospective observational study. Setting: District general hospital.Population: Women with singleton pregnancies with low PAPP-A, attending Heatherwood and Wexham Park Hospital for first trimester combined screening for Down syndrome.Methods: Data was collected from Astraia Database and CMiS maternity system. Multiple linear regression models for birth weight and gestational age at delivery were developed after adjusting for confounding variables. Logistic regressions were dichotomised for preterm delivery into <34 weeks and ≥ 34 weeks, birth weight centiles, into <10 th centile and ≥10 th centile, and pre-eclampsia versus no pre-eclampsia. Main outcome measures:Preterm birth, small for gestational age (SGA) and pre-eclampsia.Results: PAPP-A levels of ≤0.4MoM is associated with SGA <10 th centile at p=0.04 with a positive predictive value (PPV) of 83.3% and negative predictive value (NPV) of 79.3%. Similarly, association with preterm birth <34 weeks is also significant at p=0.05 with PPV of 66% and NPV of 87.4%. A significant association with pre-eclampsia (p=0.6) could not be identified. In our study data of PAPP-A ≤0.4 MoM, for every 0.1MoM fall in PAPP-A, there was a reduction in birth weight by 78gm and an earlier birth by 5.3 days. Conclusion:There is an increased likelihood of preterm delivery and SGA with progressive reduction of PAPP-A levels below ≤0.4 MoM.

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Role of the IGF system in trophoblast invasion and pre-eclampsia

Cited by 153 publications

References 26 publications

Expression of genes involved in the embryo–maternal interaction in the early-pregnant canine uterus

Expression of genes involved in the embryo–maternal interaction in the early-pregnant canine uterus

Distinct expression and localization of serine protease HtrA1 in human endometrium and first‐trimester placenta

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

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