Modulation of PAPP-A Expression By PPARγ in Human First Trimester Trophoblast☆

Handschuh, Karen; Gadrey, Jean; Guesnon, Mickaël; Laurendeau, Ingrid; Évain-Brion, Danièle; Fournier, Thierry

doi:10.1016/j.placenta.2005.10.012

Cited by 46 publications

(39 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the analysis of PPARg-target genes in human trophoblast led to characterization of new factors engaged in the regulation of trophoblast invasion [82,83,96]. Among those, heme-oxygenase-1 (HO-1), human placental growth hormone (hPGH), the pregnancy-associated plasma protein (PAPP-A) and hCG seems to have a significant role in this process [97][98][99]. Moreover, the role of PPARs in the immune response and immunotolerance during trophoblast invasion cannot be neglected [100].…”

Section: Ppars In the Placentamentioning

confidence: 99%

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

Bogacka

Kurzyńska

Bogacki

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) belong to a ligand-dependent nuclear receptor family. In the past decade, numerous studies have revealed the presence and significance of PPARs in the reproductive system. PPARs are expressed at different levels of hypothalamic-pituitary-gonadal (HPG) axis. They are also present in the uterus as well as in the placenta and embryonic tissues of different species. PPARs significance has been reported during the estrous/menstrual cycle and pregnancy with the gamma isoform studied most frequently. Several studies indicate that PPARs regulate proliferation of ovarian cells, tissue remodeling and steroidogenesis. In the endometrium, PPARs are engaged in the regulation of prostaglandins, steroids and cytokines synthesis. The role of PPARs in the trophoblast differentiation, maturation and invasion as well as in the embryo development has also been demonstrated. In this review, we summarize current findings concerning the role of PPARs in the regulation of reproductive functions at different levels of the HPG axis during various physiological statuses of females. In addition, the role of PPARs in the modulation of uterine functions as well as the placenta and embryo development has also been discussed.

show abstract

Section: Ppars In the Placentamentioning

confidence: 99%

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

Bogacka

Kurzyńska

Bogacki

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…Most of the PAPP-A is synthesized in the placental syncytiotrophoblast [16] and all proMBP is synthesized in extravillous cytotrophoblasts [17] from where it is secreted without propeptide cleavage. The process of PAPP-A/proMBP complex formation occurs in the extracellular, probably at the surface of the syncytiotrophoblast.…”

Section: Papp-a In Pregnancymentioning

confidence: 99%

“…Decreased levels of PAPP-A are found in association with abnormal placental function which has formed the basis for the first trimester screening of fetal Down syndrome [13,16]. Low first trimester maternal serum levels are found not only in trisomy 21, trisomy 18 and trisomy 13, but also in non-Down syndrome fetal aneuploidies.…”

Section: Papp-a In Pregnancymentioning

confidence: 99%

First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome

Shiefa¹,

Amargandhi²,

Bhupendra³

et al. 2012

Ind J Clin Biochem

View full text Add to dashboard Cite

The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free b-human chorionic gonadotrophin (free b-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 ? 0-13 ? 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 ? 0-13 ? 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free b-hCG is increased whereas in trisomies 18 and 13 free b-hCG is decreased.Prenatal screening for trisomies based on the analysis of biochemical markers in maternal serum has become an established part of obstetric practice in many countries. Resent interest in prenatal screening for trisomies has focused on the first trimester. Of the biochemical markers that have been investigated, only maternal serum free b-human chorionic gonadotrophin (free b-hCG) and pregnancy associated plasma protein-A (PAPP-A) has been shown to be of value. The goal of first trimester maternal serum screening programs is to identify women at increased risk of having a baby affected with Down syndrome, Patau syndrome, and Edward syndrome defects and those that will benefit from the testing.The association between advancing maternal age [1] and increased risk of trisomy 21 (Table 1) is well known, and pregnant women older than 35 years at delivery are routinely offered invasive prenatal diagnostic testing. The most commonly used test for genetic diagnosis is amniocentesis, but the rate of spontaneous fetal loss related to amniocentesis averages about one in every 200 [2] procedures. Because of this risk, serum analyte testing has become an important, noninvasive first step in detecting patients at risk for congenital abnormalities.Current studies done on first trimester maternal serum screening has shown that the double marker test helps to identify 90 % of women at risk for Down syndrome, 94 % of all major chromosomal defects such as Patau syndrome, Edward syndrome, triploidy and Turner syndrome, and 60 % of other chromosomal defects, such as deletions, partial trisomies, unbalanced translocations, and sex chromosome aneuploidies other than turners [3]. Some of the advantages of first-trimester biochemical screening over second trimester biochemical screening include providing clinicians and patients with the substantial advantage of an earlier diagnosis, higher detection rates for fetal Down syndrome i.e; 90 % [4] or even higher, compared to 80 % for the second trimester quadruple test [5,6] and 70 % for the older triple screening test [7], and detection of most major chromosome abnormalities other than trisomy 21. It also acts as a nonspecific marker for other birth defects inclu...

show abstract

“…Figure 1) The first model consists of primary cultures of trophoblastic cells isolated by gentle enzymatic digestion from first trimester chorionic villi and purified as previously described (Tarrade et al, 2001aand 2001b, Handschuh et al, 2006a. Cultured on an extra cellular matrix such as Matrigel, these cells are non proliferative and express specific markers of invasive EVCT such as cytokeratin 7 (CK7), human leukocyte antigen-G (HLA-G), human placental lactogen (hPL), the protooncogene c-erbB2, CD9 and the alpha5 subunit of the alpha5-beta1 fibronectin receptor (Tarrade et al, 2001a and2001b;Pavan et al, 2003).…”

mentioning

confidence: 99%

Role of nuclear receptors and their ligands in human trophoblast invasion

Fournier

Handschuh

Tsatsaris

et al. 2008

Journal of Reproductive Immunology

View full text Add to dashboard Cite

Human implantation involves a major invasion of the uterus wall and a complete remodelling of the uterine arteries by the extravillous cytotrophoblasts (EVCT). Abnormality of these early steps of placental development leads to poor placentation, fetal growth defects and is very often associated with preeclampsia, a major and frequent complication of human pregnancy. To study the mechanisms that control trophoblast invasion during early placental development and to provide new insight in the understanding of preeclampsia, we have developed in vitro models of human invasive trophoblasts. We showed that activation of the ligand-activated nuclear receptor PPAR with synthetic (rosiglitazone) or natural (15deoxyPGJ 2 ) agonists inhibits the trophoblastic invasion process. Analysis of PPAR-target genes revealed that placental growth hormone and the protease PAPP-A might be involved in the PPAR-mediated effect in an autocrine manner. We next investigated for PPAR ligands at the maternofetal interface and showed that oxidized-LDLs are present in EVCT in situ and decrease trophoblast invasion in vitro. Analysis of oxidized-LDLs revealed that they contain potent PPAR agonists such as eicosanoids but also high levels of oxysterols, which are specific ligands for the liver X receptor. The isoform ß of LXR was found in EVCT in situ, and activation of LXRß with synthetic or natural ligands inhibits trophoblast invasion in vitro.Together, our data underscore a major role for PPAR and LXRß in the control of human trophoblast invasion and suggest that excess of ligands such as oxidized-LDLs at the implantation site might contribute to the development of preeclampsia. 3 Development of human placentaImplantation of the human conceptus involves the invasion of the uterine epithelium and the underlying stroma by extra embryonic trophoblastic cells, which undergo a complex process of proliferation, migration and differentiation. One particularity of human placentation is the very high degree of trophoblast invasion during the first trimester (Aplin, 1991) unparalleled in other mammals. The trophoblasts named extravillous cytotrophoblasts (EVCT) invade the uterine wall and the associated arterioles where they replace the endothelial lining and most of the musculoelastic tissue of the vessel wall. This arteriole remodelling leads to low resistance vessels that provide adequate supply of maternal blood for fetal growth (Loke and King, 1995). The human trophoblastic invasion, unlike tumour invasion, is precisely regulated. It is temporally restricted to early pregnancy and it is spatially confined to the endometrium, the first third of the myometrium and the associated uterine arterioles (Fisher and Damsky, 1993;Redman, 1997). Trophoblast migration and invasive capacity have been shown to be modulated by numerous factors including oxygen concentration (Zhou et al, 1998), transforming growth factor (TGF-), IGF-II and IGFBP-1 (Irving and Lala, 1995;Hamilton et al, 1998), epidermal growth factor (Bass et al, 1994) and hepato...

show abstract

Modulation of PAPP-A Expression By PPARγ in Human First Trimester Trophoblast☆

Cited by 46 publications

References 48 publications

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome

Role of nuclear receptors and their ligands in human trophoblast invasion

Contact Info

Product

Resources

About