The Distribution of Activin and Activin Receptors in Gestational Tissues Across Human Pregnancy and During Labour

Schneider-Kolsky, Michal Elisabeth; Manuelpillai, Ursula; Waldron, Keneth; Dole, Anna; Wallace, Euan M.

doi:10.1053/plac.2002.0787

Cited by 50 publications

(24 citation statements)

References 36 publications

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“…The ability of the antibody to detect myostatin was confirmed by Western blot of the recombinant myostatin protein and positive staining of muscle tissues in which the myostatin was initially identified (1) (Figures 1, 2, and 3B). Localizations of myostatin's receptor, ACTRIIB, as well as myostatin's inhibitor, follistatin like-3 (FSTL-3), have previously been identified in human cytotrophoblasts, syncytiotrophoblasts, endothelial cells, and placental blood vessels (27)(28)(29). The mRNA expression of myostatin and ACTRIIB were confirmed by PCR in all tissues and cells used in this study.…”

Section: Discussionsupporting

confidence: 71%

Myostatin Is Localized in Extravillous Trophoblast and Up-Regulates Migration

Peiris

Salomón

Payton

et al. 2014

The Journal of Clinical Endocrinology & Metabolism

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Context: Myostatin is a highly conserved secretory protein that negatively regulates muscle development by affecting both proliferation and differentiation of muscle cells. In human placentae the expression of myostatin is negatively correlated with gestational age, and in placental explants, myostatin acts to facilitate glucose uptake. Myostatin expression is known to be higher in the placentae of pregnancies complicated by preeclampsia. Proper placental development is crucial for a healthy and successful pregnancy. Alterations to the function of the placental cells after treatment with myostatin have not previously been published.Objective: This study investigated the localization of myostatin in extravillous trophoblast (EVT) of human placentae. Furthermore, the effect of myostatin treatment on the proliferative and migrative capabilities of these placental cells was investigated.Results: Myostatin is localized in EVT, as identified by the immunohistochemistry of third-trimester placentae and immunocytochemistry of first-trimester EVT isolations positively staining for myostatin and human leukocyte antigen-G. Treatment of an EVT cell line (HTR-8/SVneo) and primary isolated EVT with varied concentrations of myostatin resulted in a significant increase in the proliferation (HTR-8/SVneo; P Ͻ .0001) and migration (HTR-8/SVneo and primary isolated EVT; P Ͻ .05), with proliferation being dose dependent and migration being dose independent. Conclusions:Myostatin localization was positively identified in EVT. Myostatin positively affected proliferation (HTR-8/SVneo) and migration of EVT (HTR-8/SVneo and primary isolated EVT). For the first time, the effect of myostatin treatment on placental cells is described. The results provide a base from which further in vitro investigations on myostatin's ability to modulate placental cell function can be made. (J Clin Endocrinol Metab 99: E2288 -E2297, 2014)

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Section: Discussionsupporting

confidence: 71%

Myostatin Is Localized in Extravillous Trophoblast and Up-Regulates Migration

Peiris

Salomón

Payton

et al. 2014

The Journal of Clinical Endocrinology & Metabolism

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“…In pregnancy, the placenta is the major source of activin in the maternal circulation (de Kretser et al 1994, Qu & Thomas 1995, Wallace & Healy 1996, Fowler et al 1998, secreting predominantly activin A (Fowler et al 1998). Maternal serum levels of activin A increase from about mid-pregnancy to a peak close to term (Muttukrishna et al 1996, Fowler et al 1998, Schneider-Kolsky et al 2002, falling quickly after birth (Fowler et al 1998). In pregnancies complicated by placental dysfunction as evidenced by intrauterine foetal growth restriction (Bobrow et al 2002, Barkehall-Thomas et al 2006 or preeclampsia (Muttukrishna et al 1997, D'Antona et al 2000, Manuelpillai et al 2001, Silver et al 2002, maternal serum levels of activin A are significantly higher than observed in normal pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress increases placental and endothelial cell activin A secretion

Mandang

Manuelpillai

Wallace

2007

Journal of Endocrinology

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Circulating levels of activin A are significantly increased in women with preeclampsia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin b A in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preeclampsia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139 . 1G27 . 4 per mg wet weight vs 322 . 9G 89 . 7 pg/ml per mg wet weight, PZ0 . 02) and from HUVECs (1 . 2G0 . 2 vs 3 . 2G1 . 8 ng/ml, PZ0 . 04). There was no effect on activin A output from monocytes. X/XO significantly increased b A mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preeclampsia when compared with controls (333 . 8G70 vs 176 . 3G 26 . 2 pg/ml, PZ0 . 04 and 49 . 5G7 vs 13 . 1G1 . 2 ng/ml, P!0 . 001 respectively). In the women with preeclampsia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated (r 2 Z0 . 72; P!0 . 001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preeclampsia.

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“…However, betaglycan is also involved in the inhibin A and activin A pathways, as it mediates the passage of inhibin A activity into cells and prevents activin A binding to ActRI, thus antagonizing activin A. Activin A and inhibin A are localized in maternal decidual, amniotic and chorionic cells and in the syncytial layer of placental villi (4, 6, 10 -12), the cytotrophoblast remaining unstained. In the light of these findings, we can conclude that the localization of betaglycan overlaps with that of the TGF-b and related receptors, with activin/inhibin bA and a subunits, and with activin receptors (13,14).…”

Section: Discussionmentioning

confidence: 77%

“…In contrast, inhibin A is not able to affect directly either the secretion of GnRH, progesterone, hCG and prostaglandin E 2 (4, 6, 15), or placental growth and differentiation (5). Thus the lack of inhibin A activity may be attributable to the fact that betaglycan is not expressed by cytotrophoblast and amniotic cells whereas, in contrast, activin exerts an effect because its receptors are localized on the cytotrophoblast and syncytiotrophoblast, and amniotic cells (14).…”

Section: Discussionmentioning

confidence: 99%

“…Activin/ inhibin receptors (such as ActRI and ActRII) have been immunolocalized in placental endothelial cells mainly at term (14), whereas betaglycan staining has been demonstrated only in tissues of early pregnancy. Because activin A is involved in endothelial proliferation and angiogenesis (18,19), the localization of betaglycan and ActRs in vascular endothelial cells of decidual (13) and villous (14) blood vessels suggests a role for betaglycan in modulating the effect of activin A on vascular adaptations to pregnancy in concert with TGF-b. Furthermore, although inhibin A is without effect on vascular endothelial cell growth (19), TGF-b, in contrast, is an important modulator of endothelial functions (20).…”

Section: Discussionmentioning

confidence: 99%

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Expression of betaglycan in pregnant tIssues throughout gestation

Ciarmela

Florio²,

Toti³

et al. 2003

European Journal of Endocrinology

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Background: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of transforming growth factor-b (TGF-b), inhibin and activin activities into cells. TGF-b and inhibin-related proteins are growth factors that are expressed by several tissues and in pregnancy. They have a function in modulating the growth, differentiation and invasion of the placental trophoblast. Objective: To evaluate whether betaglycan is expressed by intrauterine tissues throughout gestation. Design and methods: Expression of betaglycan mRNA and protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in trophoblast, decidua and fetal membranes collected during the first (n ¼ 6 elective terminations of pregnancy, between 8 and 12 gestational weeks) and third (n ¼ 6 elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy. Results: Betaglycan mRNA was expressed by all gestational tissues, independently of gestational age. Immunoreactive protein was found in decidual cells and in some chorionic, but not epithelial, amniotic cells. With respect to the placental localization, syncytiotrophoblast, but not cytotrophoblast, cells were intensively stained both in the placental bed and in the villous trophoblast, and in some cells within the stroma of terminal villi, of the first and third trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the endothelial cells of decidual vessels in both the first and third trimesters of pregnancy, whereas endothelial cells of fetal blood vessels in the villous were clearly represented only in first trimester samples, not in those of term placenta. Conclusions: Betaglycan mRNA and peptide are expressed by the trophoblast, the decidua and the fetal membranes, but the localization of the peptide in vessel walls is dependent on gestational age.

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The Distribution of Activin and Activin Receptors in Gestational Tissues Across Human Pregnancy and During Labour

Cited by 50 publications

References 36 publications

Myostatin Is Localized in Extravillous Trophoblast and Up-Regulates Migration

Myostatin Is Localized in Extravillous Trophoblast and Up-Regulates Migration

Oxidative stress increases placental and endothelial cell activin A secretion

Expression of betaglycan in pregnant tIssues throughout gestation

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