The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4‐vessel sampling

Michelsen, Trond M.; Henriksen, Tore; Reinhold, Dominik; Powell, Theresa L.; Jansson, Thomas

doi:10.1096/fj.201801193r

Cited by 28 publications

(30 citation statements)

References 56 publications

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“…In vitro studies show that both VEGF and PlGF are produced by the placenta 25 . Intriguingly, in contrast with PlGF, in vivo data suggests that maternal circulating VEGF is taken up by the placenta and mostly produced by peripheral organs (shown by a lower concentration of VEGF in the uterine vein when compared to the radial artery) 10 . This not only demonstrates the value of in vivo data, but also has important implications.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have examined in vivo PlGF placental production by interrogating the PlGF concentration gradient between the uterine vein (closer to placenta) and a peripheral vein. Whilst a difference has been shown by one group 8,10 , implicating the placenta as a main source of PlGF, this was not shown by another 9 . This discrepancy could be due to different methodologies used.…”

mentioning

confidence: 84%

“…Since then however, PlGF has been found to be produced by malignant cells, endothelium, smooth muscle, pericytes, myocites and immune cells [5][6][7] . In vivo studies in pregnancy show conflicting data as to the primary source of PlGF [8][9][10] . The question remains as to how much maternal circulating PlGF is of placental origin.…”

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confidence: 99%

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In vivo evidence of significant placental growth factor release by normal pregnancy placentas

Cerdeira

Kandžija

Pärgmäe

et al. 2020

Sci Rep

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Placental growth factor (PlGF) is an angiogenic factor identified in the maternal circulation, and a key biomarker for the diagnosis and management of placental disorders. Furthermore, enhancing the PlGF pathway is regarded as a promising therapy for preeclampsia. The source of PlGF is still controversial with some believing it to be placental in origin while others refute this. To explore the source of PlGF, we undertook a prospective study enrolling normal pregnant women undergoing elective caesarean section. The level of PlGF was estimated in 17 paired serum samples from the uterine vein (ipsilateral or contralateral to the placental insertion) during caesarean section and from a peripheral vein on the same day and second day post-partum. PlGF levels were higher in the uterine than in the peripheral vein with a median difference of 52.2 (IQR 20.1-85.8) pg/mL p = 0.0006. The difference when the sampled uterine vein was ipsilateral to the placenta was 54.8 (IQR 37.1-88.4) pg/mL (n = 11) and 23.7 (IQR −11; 70.5) pg/mL (n = 6) when the sample was contralateral. Moreover, PlGF levels fell by 83% on day 1-2 post-partum. Our findings strongly support the primary source of PlGF to be placental. These findings will be of value in designing target therapies such as PlGF overexpression, to cure placental disorders during pregnancy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 84%

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In vivo evidence of significant placental growth factor release by normal pregnancy placentas

Cerdeira

Kandžija

Pärgmäe

et al. 2020

Sci Rep

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“…(4)(5)(6)(7)(8)(9) Research interest has recently grown regarding GDF15 during pregnancy as substantial and progressive increases in serum GDF15 have been shown from early to late pregnancy, ending up with serum levels much higher than in any other physiological or pathophysiological state. (10)(11)(12)) Pregnancy is marked by major metabolic and physiological changes, such as increases in appetite, body weight, insulin resistance and inflammation. (13,14) GDF15 may play an important role in all these areas, and has been found during pregnancy to be linked to altered glucose metabolism, (12,15) and pregnancy-induced nausea.…”

Section: Introductionmentioning

confidence: 99%

Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

Andersson‐Hall

Svedin

Mallard

et al. 2021

Preprint

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Aim Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. Methods Women were sampled at elective caesarean section (n=45, BMI=28.1±5.0) and were followed up 5 years after pregnancy (n=25). GDF15, insulin and leptin were measured in CSF and serum. In addition, glucose, adiponectin and Hs-CRP were measured in blood. Results GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, p<0.001) and serum (73789±29198 vs. 404±102 ng/l, p<0.001). CSF levels correlated with serum levels during pregnancy (p<0.001), but not in the non-pregnant state (p=0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (p<0.001), previously linked to pregnancy-induced nausea. Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. Conclusion This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.

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“…Maternal GDF15 levels have been reported to increase across gestation, probably due to placental expression 18,19 , and high levels of GDF15 have been linked to pregnancy-related nausea and hyperemesis 20,21 . However, it is not known how GDF-15 levels increase during pregnancy in normoglycemic women that differ in body mass index (BMI) and whether these levels are linked to changes in insulin resistance and insulin secretory function.…”

Section: Introductionmentioning

confidence: 99%

Growth differentiation factor 15 levels in obese and healthy pregnancies and its relation to insulin resistance and insulin secretory function: a longitudinal study during and after pregnancy

Andersson‐Hall

Joelsson

Svedin

et al. 2020

Preprint

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Objective/aim Growth-differentiation-factor 15 (GDF15) has been suggested to improve or protect beta-cell function. During pregnancy, beta-cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta-cell function by homeostatic model assessment (HOMA). Methods The cohort participants were 38 NW (BMI 22.3±1.7) and 35 OB (BMI 35.8±4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12, and 18 months postpartum. Fasting glucose, insulin, and GDF15 were measured, and HOMA for insulin resistance (HOMA-IR) and beta cell function (HOMA-B) determined. Results GDF15 levels increased significantly each trimester and were˜200-fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB in T3, but was lower in NW at 18 months after pregnancy. GDF15 correlated inversely with BMI and fat-free mass at T3. Low GDF15 in T1 was associated with lower incidence of nausea and with carrying a male fetus. GDF15 at T2 and T3 and the increases between trimesters associated with increased HOMA-B over the course of pregnancy. Increases in GDF15 either early or late in pregnancy were associated with a reduction in blood glucose between T2 and T3. Conclusion Large gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy-induced insulin resistance. Abbreviations GDF15 Growth differentiation factor 15 HOMA-B Homeostatic model assessment for beta cell function HOMA-IR Homeostatic model assessment for insulin resistance NW Women of normal weight OB Women with obesity

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The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4‐vessel sampling

Cited by 28 publications

References 56 publications

In vivo evidence of significant placental growth factor release by normal pregnancy placentas

In vivo evidence of significant placental growth factor release by normal pregnancy placentas

Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

Growth differentiation factor 15 levels in obese and healthy pregnancies and its relation to insulin resistance and insulin secretory function: a longitudinal study during and after pregnancy

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