Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal membranes

Macri, Charles J.; Martı́nez, Alfredo; Moody, Terry W.; Gray, Karen; Miller, Matthew T.; Gallagher, Michael; Cuttitta, Frank

doi:10.1016/s0002-9378(96)80023-8

Cited by 75 publications

(63 citation statements)

References 18 publications

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“…9,10 We and others have shown a progressive increase in maternal plasma ADM levels throughout pregnancy. [11][12][13][14][15][16] In PE, early reports suggested that maternal ADM levels were decreased, but subsequent larger series found no difference from controls. 14,17,18 However, we believe that this indicates a lack of compensatory increase in response to the hypertensive state.…”

mentioning

confidence: 99%

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Dakour

Kaufman

et al. 2003

Hypertension

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Abstract-To explore the mechanisms of adrenomedullin (ADM) regulation in normal and preeclamptic (PE) states, we determined placental production of ADM and ADM regulation by cytokines. Isolated, purified cytotrophoblast cultures from normal (nϭ8) and PE (nϭ10) placentas were cultured for 3 days in the absence or presence of 10 ng/mL epidermal growth factor (EGF), 1 ng/mL transforming growth factor (TGF)-␤1, 10 ng/mL tumor necrosis factor (TNF)-␣, or 100 U/mL interferon (IFN)-␥. Cells were also cultured for 3 days in 10% fetal bovine serum for determination of syncytial formation by desmoplakin staining. Pieces of normal and PE placentas were snap-frozen for ADM mRNA measurement. Results showed that basal ADM production into culture medium by radioimmunoassay was significantly lower in PE placental cells. EGF significantly stimulated ADM production in normal trophoblasts but did not in PE placentas.

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mentioning

confidence: 99%

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Dakour

Kaufman

et al. 2003

Hypertension

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“…Occasionally, immunocytochemical staining for AM has also been reported in cytotrophoblast cells and in the mesenchyma and inflammatory cells within the villi (Kanenishi et al, 2001;Macri et al, 1998). The fetal membranes, and, more specifically, the epithelium of the amniotic membrane, also show high levels of AM and its mRNA (Kanenishi et al, 2000(Kanenishi et al, , 2001Kobayashi et al, 2000;Macri et al, 1996b;Makino et al, 1999c). The pattern and intensity of AM immunoreactivity in the first trimester human placenta and fetal membranes were reported to be similar to that in term pregnancy (Macri et al, 1996a;Kanenishi et al, 2001), suggesting that AM secreted from these sites might play an important role in the maintenance of normal pregnancy throughout gestation.…”

Section: Am In Early Developmental Stages Am In Fetoplacental Tissuesmentioning

confidence: 96%

“…Interestingly, significantly higher AM concentration has been found in amniotic fluid as compared to maternal plasma at any gestational age Kanenishi et al, 2001). The amniotic membrane, placenta, and the embryo proper are candidate sources for these elevated levels in the amniotic fluid Kanenishi et al, 2001;Macri et al, 1996b). Both total AM concentration in amniotic fluid Kanenishi et al, 2001), and the mature/total AM concentration ratio (Kanenishi et al, 2001) were significantly increased in late gestation.…”

Section: Clinical Aspects Related To the Levels Of Am In Normal Pregnmentioning

confidence: 99%

“…Future studies should elucidate the putative importance of this AM increase in the amniotic fluid on fetal organ development and/or maturation at this gestational period. Besides, AM has also been shown to have antimicrobial activity (Allaker et al, 1999;Walsh et al, 1998), and thus a protective role of AM in the amniotic fluid preventing fungal or bacterial infections during pregnancy has also been proposed (Macri et al, 1996b).…”

Section: Clinical Aspects Related To the Levels Of Am In Normal Pregnmentioning

confidence: 99%

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Adrenomedullin in mammalian embryogenesis

Garayoa

Bodegas

Cuttitta

et al. 2002

Microscopy Res & Technique

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Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

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“…17 At the cellular level, many studies have described Adm expression in several tissues derived from both the mother and the fetus: ovary, uterus, placenta and fetal membranes. [18][19][20][21][22][23][24] For example, just prior to implantation in mice, Adm is highly expressed in the trophectoderm cells of the early blastocyst and the luminal epithelial cells of the uterine lining. 20,25,26 Shortly after implantation, and during the rapid expansion of the murine decidua, Adm expression is strongly centered within the primary decidual zone, a 3-5 cell-layer thick region surrounding the recently implanted embryo which serves as a temporary and physical barrier to immunological attack.…”

Section: Am Is a Versatile Peptide Hormone Expressed By Both Maternalmentioning

confidence: 99%

Adrenomedullin and endocrine control of immune cells during pregnancy

Matson

Caron

2014

Cell Mol Immunol

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The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternalfetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies. Keywords: adrenomedullin; preeclampsia; pregnancy; spiral artery remodeling; uNK cells INTRODUCTION Pregnancy presents a mysterious immunological paradox that is permitted by the complex, unique immunology of the maternalfetal interface. We are only beginning to understand how this very specialized immune 'subsystem' differs from the systemic immune system and thus effectively protects the fetus from maternal rejection. For example, the sizable uterine natural killer (uNK) cell and macrophage populations found during early pregnancy are distinctive in their cell surface markers and functions compared to their peripheral counterparts. 1,2 Understanding the activity and control of these immune cell types will shed light on this immunological paradox and possibly inform the pathophysiology of complications of pregnancy.During the past decade, numerous studies have characterized critical roles for the peptide hormone adrenomedullin (Adm gene; AM protein) in the establishment and maintenance of a healthy pregnancy. Here, we discuss the effects of AM on implantation and placentation, concentrating on the control of the uNK cell population and its subsequent involvement in the process of spiral artery remodeling-a necessary process for the maternal vascular adaptation to pregnancy. Importantly, studies addressing the link between

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Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal membranes

Cited by 75 publications

References 18 publications

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Adrenomedullin in mammalian embryogenesis

Adrenomedullin and endocrine control of immune cells during pregnancy

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