Human placental lactogen and pregnancy‐associated plasma protein A in first trimester and subsequent fetal growth

Pedersen, Jan Fog; Sørensen, Steen; Ruge, Susanne

doi:10.3109/00016349509024379

Cited by 42 publications

(35 citation statements)

References 9 publications

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“…Perhaps the best studied of these proteases is pregnancyassociated plasma protein A (PAPP-A), which is a metalloproteinase secreted by the decidua and placenta into maternal circulation where it is able to cleave IGFBP4 and IGFBP5 and thus increase the activity of local IGFs [73][74][75][76][77]. The levels of PAPP-A in maternal circulation during the first trimester have been found to be associated with subsequent fetal growth and birth weight [78][79][80], suggesting that the levels of placental IGFs observed very early in gestation may determine the extent of fetal growth throughout the pregnancy [79]. Low levels of PAPP-A in the first trimester of gestation have been found to be associated with intrauterine growth restriction, stillbirth, and preterm delivery [76].…”

Section: Igf1 and Igf2 Receptorsmentioning

confidence: 98%

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Callan

Milne

2009

Cancer Causes Control

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Fetal growth is determined by a complex interplay of genetic, nutritional, environmental, and hormonal factors. Greater than expected fetal growth has been positively associated with the risk of the development of some cancers in childhood, particularly acute lymphoblastic leukemia, and the biological mechanisms underlying such associations are thought to involve insulin-like growth factors (IGFs). Circulating IGF levels are highly correlated with fetal growth, and IGFs are believed to play an important role in carcinogenesis; however, these two bodies of evidence have not been well integrated and, as a result, the potential underlying biological mechanisms linking the IGF system with the development of specific childhood cancers have not been elucidated. This review aims to draw together and summarize the literature linking the IGF system, rapidity of fetal growth, and risk of some specific childhood cancers; suggest explanations for some of the inconsistencies observed in previous studies of these associations; and propose an integrated framework for the putative involvement of the IGF system in the development of at least some childhood cancers. If the challenges involved in studying the complex IGF system can be overcome, this field presents an exciting opportunity to elucidate etiological pathways to childhood malignancies.

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Section: Igf1 and Igf2 Receptorsmentioning

confidence: 98%

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Callan

Milne

2009

Cancer Causes Control

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“…Studies have shown that low free β-HCG and PAPP-A levels in the first trimester are associated with pregnancy complications. 10,11 In particular, low PAPP-A levels are significantly associated with spontaneous fetal loss, low-birth-weight babies, intra-uterine growth restriction, pregnancy-induced hypertension, preeclampsia, preterm rupture of membranes, and placental abruption. [12][13][14] Several studies have shown that women with pre-existing diabetes mellitus (DM) have significantly lower PAPP-A levels than those without DM.…”

Section: Introductionmentioning

confidence: 99%

Association between pregnancy-associated plasma protein-A levels in the first trimester and gestational diabetes mellitus in Chinese women

Wong

et al. 2015

Hong Kong Med J

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Introduction:Several studies have shown that women with pre-existing diabetes mellitus have significantly lower pregnancy-associated plasma protein-A levels than those without. This study aimed to evaluate whether first-trimester pregnancyassociated plasma protein-A multiple of median is associated with gestational diabetes mellitus in Chinese pregnant women. Methods:This prospectively collected case series was conducted in a regional hospital in Hong Kong. All consecutive Chinese women with a singleton pregnancy who attended the hospital for their first antenatal visit (before 14 weeks' gestation) from April to July 2014 were included. Pregnancyassociated plasma protein-A multiple of median was compared between the gestational diabetic (especially for early-onset gestational diabetes) and non-diabetic groups. The correlation between pregnancy-associated plasma protein-A level and glycosylated haemoglobin level in women with gestational diabetes was also examined. Results:Of the 520 women recruited, gestational diabetes was diagnosed in 169 (32.5%). Among them, 43 (25.4%) had an early diagnosis, and 167 (98.8%) with the disease were managed by diet alone. The gestational diabetic group did not differ significantly to the non-diabetic group in pregnancyassociated plasma protein-A (0.97 vs 0.99, P=0.40) or free β-human chorionic gonadotrophin multiple of median (1.05 vs 1.02, P=0.29). Compared with the non-gestational diabetic group, women with early diagnosis of gestational diabetes had a non- Association between pregnancy-associated plasma protein-A levels in the first trimester and gestational diabetes mellitus in Chinese womenNew knowledge added by this study • This is the first study to assess the association of first-trimester pregnancy-associated plasma protein-A multiple of median (PAPP-A MoM) with gestational diabetes mellitus (GDM) in a Chinese population. PAPP-A MoM was not predictive of development of non-insulin-dependent GDM in Chinese women.• There was no correlation between PAPP-A MoM and glycosylated haemoglobin level in Chinese women with GDM. PAPP-A levels were not useful to predict and identify poor glycaemic control in women with GDM.• There was a high prevalence of GDM (32.5%) in the Chinese population. Implications for clinical practice or policy • PAPP-A and β-human chorionic gonadotrophin do not seem to be predictive of non-insulin-dependent GDM.Other predictive model that comprises the maternal and clinical risk factors in Chinese women is warranted to identify women at risk of GDM.• Further studies that employ the new diagnostic criteria for GDM are warranted to examine the potential of first-trimester biochemical markers to predict GDM as well as their influence on the prevalence of GDM in the Chinese population.

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“…Therefore, PAPPA is considered as a bioactive IGF-1 promoting enzyme in the IGF system 10 . PAPPA is predominantly produced by embryonic trophoblast cells and the placenta, and its concentration in pregnant women serum is dramatically increased during the first trimester, and is continuously elevated until the end of pregnancy 11 . Notably, low circulating PAPPA levels may indicate a high risk of delivery of a small-for-gestational age infant, Down’s syndrome and preeclampsia 12–14 .…”

Section: Introductionmentioning

confidence: 99%

Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation

Wang

Liu

et al. 2017

Sci Rep

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Glycosylation of uterine endometrial cells plays important roles to determine their receptive function to blastocysts. Trophoblast-derived pregnancy-associated plasma protein A (PAPPA) is specifically elevated in pregnant women serum, and is known to promote trophoblast cell proliferation and adhesion. However, the relationship between PAPPA and endometrium receptivity, as well as the regulation of N-fucosylation remains unclear. We found that rhPAPPA and PAPPA in the serum samples from pregnant women or conditioned medium of trophoblast cells promoted endometrium receptivity in vitro. Moreover, rhPAPPA increased α1,2-, α1,3- and α1,6-fucosylation levels by up-regulating N-fucosyltransferases FUT1, FUT4 and FUT8 expression, respectively, through IGF-1R/PI3K/Akt signaling pathway in human endometrial cells. Additionally, α1,2-, α1,3- and α1,6-fucosylation of integrin αVβ3, a critical endometrium receptivity biomarker, was up-regulated by PAPPA, thereby enhanced its adhesive functions. Furthermore, PAPPA blockage with antibody inhibited embryo implantation in vivo, mouse embryo adhesion and spreading in vitro, as well as N-fucosylation level of the endometrium in pregnant mice. In summary, this study suggests that PAPPA is essential to maintain a receptive endometrium by up-regulating N-fucosylation, which is a potential useful biomarker to evaluate the receptive functions of the endometrium.

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Human placental lactogen and pregnancy‐associated plasma protein A in first trimester and subsequent fetal growth

Abstract: Higher levels of human placental lactogen and pregnancy-associated plasma protein A predicted earlier delivery, maybe because of better fetal growth, and higher levels of pregnancy-associated plasma protein A predicted better fetal growth.

Cited by 42 publications

References 9 publications

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Association between pregnancy-associated plasma protein-A levels in the first trimester and gestational diabetes mellitus in Chinese women

Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation

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