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    علم الأجنة

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    bessaannn123

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    © All Rights Reserved
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    علم الأجنة

    Uploaded by

    bessaannn123
    6 views8 pages

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    © © All Rights Reserved

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    6 views8 pages

    علم الأجنة

    Uploaded by

    bessaannn123

    Copyright:

    © All Rights Reserved
    Download as DOCX, PDF, TXT or read online from Scribd
    Download as docx, pdf, or txt
    of 8

    Collage of Science and Technology

    Dept.Biology
    .Name:Bisan Talahma

    .Course: Embryology

    .Instructor Name: Dr. Khaldoun Nijem

    .Role of PAPP-A in Pregnancy


    Role of PAPP-A in Pregnancy:

    *Biochemical Function:

    PAPP-A is a large glycoprotein produced by the placental


    syncytiotrophoblasts.
     It functions as a metalloproteinase that specifically cleaves
    IGFBPs (insulin-like growth factor binding proteins),
    particularly IGFBP-4 and IGFBP-5, which regulate the
    availability of IGFs (insulin-like growth factors).
    The six IGFBPs all bind IGFs with higher affinity than the IGF1
    receptor (IGF1R). Therefore, the decrease of IGF affinity for
    the IGFBPs, resulting from in vitro proteolytic cleavage, will
    lead to an increase of IGF signalling.

    *Insulin-like Growth Factors (IGFs) :

    The biological activity of insulin-like growth factors (IGFs)-I


    and -II is tightly regulated by six different, but homologous,
    IGF binding proteins (IGFBP-1–6) . Cleavage in the central
    region of IGFBPs causes dissociation of bound IGF, and
    such limited proteolysis is a powerful means by which the
    bioavailable concentration of IGF is locally regulated .
    Although a large number of biological fluids and
    conditioned media have been shown to contain specific
    proteolytic activity against one or more of the IGFBPs, the
    identities of the proteinases have remained unknown in
    most cases. One exception is the IGFBP-4 proteinase
    secreted by human fibroblasts, which has recently been
    identified as pregnancy-associated plasma protein-A
    (PAPP-A), a high-molecular-weight protein not previously
    connected with the IGF system . Several other sources of
    IGFBP-4 proteolytic activity have now been investigated,
    and PAPP-A has been shown to be the responsible
    proteinase .
    Based primarily on the presence of an elongated zinc-binding
    motif in the amino acid sequence, PAPP-A belongs to the
    metzincin superfamily of metalloproteinases .
     IGFs, primarily IGF-1 and IGF-2, are critical for cellular
    growth and development. They play a significant role in fetal
    growth by promoting cell proliferation and differentiation.
     IGF-1 is crucial for embryonic and fetal development, while
    IGF-2 is important for placental growth and nutrient transfer
    to the fetus.
    a novel autosomal recessive syndrome consisting of
    short stature, skeletal abnormalities, and high
    circulating IGF-1, IGFBP-3, IGFBP-5, and acid labile
    subunit (ALS) levels due to loss-of-function mutations in
    the pregnancy-associated plasma protein-A2 (PAPP-A2,
    pappalysin 2) gene (1). PAPP-A2 is a metalloproteinase
    that specifically cleaves IGFBP-3 and -5, resulting in
    dissociation of IGFs carried within ternary complexes
    with ALS and IGFBP-3 or -5, enabling unbound IGF to
    enter the extravascular space to stimulate the IGF-1
    receptor (IGF-1R) in target tissues .
    *Placental Development:

    The human placenta undergoes radical changes during the


    first trimester of pregnancy. The implantating conceptus
    embeds itself within the uterine endometrium and the
    placental trophoblastic tissue surrounds the gestational sac.
    By the end of the first trimester, two thirds of the primitive
    placenta disappears and the position of the placenta can be
    determined . The early trophoblastic tissue in the placenta is
    not able to produce enough of the steroids – the most
    important of which is progesterone – required to maintain the
    pregnancy; the steroids are produced by the corpus luteum
    up to the 8th pregnancy week, after which the placenta is
    capable of sufficient steroid synthesis . The earliest stages of
    fetal development take place in a low oxygen environment
    inside the gestational sac . By the end of the first trimester,
    the fetoplacental blood flow is established, after trophoblastic
    cells have invaded the myometrium superficially and
    remodeled the uterine spiral arteries to ensure sufficient
    maternal blood flow in the intervillous space of the placenta.

    Any disturbance in the placentation and trophoblastic


    invasion may cause immediate or later complications, such as
    miscarriage, intrauterine growth restriction (IUGR),
    preeclampsia, and preterm delivery . Placental proteins like
    Pregnancy Associated Protein A (PAPP-A), A Disintegrin and
    Metalloproteinase 12 (ADAM12) and Placental Protein 13
    (PP13) have been used to screen for chromosomal anomalies
    during the first trimester; they also seem to be capable of
    predicting adverse outcomes later in the pregnancy .These
    proteins are thought to be involved in normal implantation
    and placental development .

    The majority of current knowledge concerning the secretion


    of PAPP-A, ADAM12 and PP13 during the first trimester is
    based on cross-sectional data from studies evaluating their
    effectiveness on Down syndrome screening . The relationship
    between the growth of the placenta and the gestational sac
    and the secretion of PAPP-A, ADAM12 and PP13 in normal
    pregnancies has not been established.
    :Fetal Growth*
    Plasma protein-A is produced in the human placenta (PAPP- .
    A) and has a regulatory effect on insulin-like growth factor
    (IGF) concentration, by means of proteolysis of the insulin-
    like growth factor binding protein (IGFBP). IGF acts locally to
    promote mitosis and cellular differentiation; it has effects on
    both embryogenesis and the regulation of foetal and placental
    growth. As a consequence of this latter function, PAPP-A is
    .considered as a regulator of cell growth and proliferation
    Pregnancy outcomes associated with low PAPP‐A levels

    there was a higher rate of Caesarian Sections (28.9%) in the


    low PAPP-A group compared to local (20.6%) and national
    (26.2%) data in the same time frame. Lower levels of PAPP-A
    were associated with higher caesarian section rates 38.1%
    (0.11-0.20 MoM) versus 24.2% (0.31-0.40 MoM). Conversely,
    normal vaginal delivery was more common with a higher
    PAPP-A at 62.4% (0.31-0.40 MoM) verses 45.5% in the 0.11-0.20
    MoM group. Twenty-four percent of women underwent
    induction of labour, 24% of these for presumed intrauterine
    .growth restriction
    A lower PAPP-A level was associated with a higher incidence
    of maternal complications such as diabetes and pregnancy
    induced hypertension (PIH) 33.3% in the lowest level of PAPP-
    A (0.40 MoM). The overall rate of maternal complications in
    the cohort was 17.7% with the most prevalent maternal
    complications being Diabetes (30.2%), Pregnancy Induced
    .Hypertension (28.3%) and Polyhydramnios (15.1%)
    Lower levels of PAPP-A are associated with an increase in
    adverse maternal complications and an increase in Caesarian
    Section rate. It also confirms that there is an association
    between low PAPP-A and small for gestational age babies and
    .preterm birth
    :References

    Svensson AC, Cnattingius S, Lichtenstein P Pawitan Y, .1


    Cnattingius S, Reilly M, Lichtenstein P. Familial aggregation of
    small-for-gestational-age births: the importance of fetal
    .genetic effects. Am J Obstet Gynecol. 2006 Feb;194(2):475–9
    Basso O, Weinberg CR Wilcox AJ, Weinberg CR. Birth .2
    weight and mortality: causality or confounding? Am J
    .Epidemiol. 2006 Aug 15;164(4):303–11

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