Genetic Disorders and the Fetus. Группа авторов
Milunsky A, Bender CS. Failure of amniotic‐fluid cell growth with toxic tubes. N Engl J Med 1979; 301:47.
667 667. Kohn G. Failure of amniotic fluid cell cultures due to syringe toxicity. Prenat Diagn 1981; 1:233.
668 668. Chiesa J, Bureau JP. Nothing ventured, nothing gained! Prenat Diagn 1999; 19:894.
669 669. Seguin LR, Palmer CG. Variables influencing growth and morphology of colonies of cells from human amniotic fluid. Prenat Diagn 1983; 3:107.
670 670. Felix JS, Doherty RA. Amniotic fluid cell culture II. Evaluation of a red blood cell lysis procedure for culture of cells from blood‐contaminated amniotic fluid. Clin Genet 1979; 15:215.
671 671. Johansson KE, Bolske G. Evaluation and practical aspects of the use of a commercial DNA probe for detection of mycoplasma infections in cell cultures. J Biochem Biophys Methods 1989; 19:185.
672 672. Knutsen T. Laboratory safety, quality control and regulations. In: Barch MJ, ed. The AGT cytogenetics laboratory manual, 3rd edn. Philadelphia: Lippincott Williams & Wilkins, 1997:597.
673 673. Holtge GA. Laboratory safety. In: McClatchey KD, ed. Clinical laboratory medicine, 2nd edn. Philadelphia: Lippincott Williams & Wilkins, 2002:78.
674 674. Travers EM. Basic laboratory management. In: McClatchey KD, ed. Clinical laboratory medicine, 2nd edn. Philadelphia: Lippincott Williams & Wilkins, 2002:3.
675 675. Tsai MS, Lee JL, Chang YJ, et al. Isolation of human multipotent mesenchymal stem cells from second‐trimester amniotic fluid using a novel two‐stage culture protocol. Hum Reprod 2004; 19:1450.
676 676. De Coppi P, Bartsch G, Jr., Siddiqui MM, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007; 25:100.
677 677. Guillot PV, Gotherstrom C, Chan J, et al. Human first trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells 2007; 25:646.
678 678. Roubelakis MG, Pappa KI, Bitsika V, et al. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells. Stem Cells Dev 2007; 16:931.
679 679. Zhou J,Wang D, Liang T, et al. Amniotic fluid‐derived mesenchymal stem cells: characteristics and therapeutic applications. Arch Gynecol Obstet 2014; 290:223.
680 680. In't Anker PS, Scherjon SA, Kleijburg‐van der Keur C, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 2003; 102:1548.
681 681. Trounson A. A fluid means of stem cell generation. Nat Biotechnol 2007; 25:62.
682 682. Liu YW, Roan JN, Wang SP, et al. Xenografted human amniotic fluid‐derived stem cell as a cell source in therapeutic angiogenesis. Int J Cardiol 2013; 168:66.
683 683. Petsche Connell J, Camci‐Unal G, Khademhosseini A, et al. Amniotic fluid‐derived stem cells for cardiovascular tissue engineering applications. Tissue Eng Part B Rev 2013; 19:368.
684 684. Kang NH, Hwang KA, Kim SU, et al. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid‐derived stem cells. Cancer Gene Ther 2012; 19:517.
685 685. Kaviani A, Perry TE, Dzakovic A, et al. The amniotic fluid as a source of cells for fetal tissue engineering. J Pediatr Surg 2001; 36:1662.
686 686. Gucciardo L, Lories R, Ochsenbein‐Kolble N, et al. Fetal mesenchymal stem cells: isolation, properties and potential use in perinatology and regenerative medicine. BJOG 2009; 116:166.
687 687. Murphy SV, Atala A. Amniotic fluid and placental membranes: unexpected sources of highly multipotent cells. Semin Reprod Med 2013; 31:62.
4 Molecular Aspects of Placental Development
Wendy P. Robinson1,2 and Deborah E. McFadden1,2
1BC Children's Hospital Research Institute, Vancouver, BC, Canada
2University of British Columbia, Vancouver, BC, Canada
Overview
The placenta is a fetal organ that is discarded after birth, but is essential to ensuring normal development in utero. It regulates fetal growth, protects the fetus from infection and other adverse exposures, as well as generally programming the fetus for good health after birth. Screening for placental disease is an important component to the assessment of the fetus in pregnancy. Reduced placental efficiency can lead to fetal growth restriction (FGR) and/or maternal preeclampsia (PE). This can be caused by genetic changes within the placenta or by environmental influences, such as maternal stress or drug exposure. In this chapter, causes of placental disease and the role of the placenta in diagnosis of fetal health will be reviewed with a focus on genetic associations.
Placental structure
Evaluating the placenta requires an understanding of its unique structure and development. The chorionic villi that compose the placenta are organized into 50–70 distinct tree‐like structures that grow in a clonal manner outwards from the chorionic plate into the basal plate (which interface with the maternal decidua).1 These villi are bathed in maternal blood, from which they sponge up nutrients important for fetal growth. The maternal blood is in direct contact with the outer trophoblast bilayer of the chorionic villi. This bilayer is made up of a multinucleated syncytium derived by fusion of the cytotrophoblast cells that form a single‐cell layer below the syncytium. In addition, some cytotrophoblasts form columns that migrate into and anchor the placenta to the uterine wall. Invasive cells that detach from these columns are termed extravillous trophoblasts (EVTs) and include the interstitial cytotrophoblasts (iCTBs) found in the decidual stroma and those that remodel maternal blood vessels, termed endovascular cytotrophoblasts (eCTBs).1 The inner core of the villi is the chorionic mesenchyme, which includes structural components, and a mix of cells including fetal blood vessels, fibroblasts, pericytes, and Hofbauer cells (placental macrophages). These extraembryonic cells derive from the epiblast of the blastocyst, from which the fetus is also derived.
Placental size is strongly correlated with fetal size; however, there is considerable variation in placental size for any given birthweight.2 The efficiency of the placenta depends on the surface area for exchange, thickness, and density of transporter proteins,3 and birthweight is highly associated with placental weight.4 Interestingly, mean placental size can vary between populations and even within a population over time because of changes in maternal nutrition or other environmental conditions.5
Placental development and function
The placenta is responsible for many functions, which change as pregnancy proceeds.1 In early gestation, the primary roles of the placenta include invasion into the maternal endometrium, remodeling of maternal vasculature, and secretion of hormones important to maintain pregnancy. The placenta subsequently regulates blood flow and nutrient delivery to the fetus, buffers the fetus from adverse environmental effects, and generally performs the functions of multiple organs (lung, brain, kidney, immune system, etc.).
Implantation
During the invasion process, the early trophoblasts produce molecules to help them attach to and invade the uterine wall (e.g. integrins), prevent menstruation (e.g. human chorionic gonadotropin (hCG)), destroy the uterine matrix (e.g. matrix metalloproteinases), and suppress the maternal immune system (e.g. corticotropin‐releasing hormone (CRH)).6, 7 hCG (encoded by CGA and CGB) is one of the earliest hormones expressed from syncytiotrophoblast and stimulates many other processes. Multiple growth factors are important in regulating trophoblast proliferation, including placental growth factor (PlGF), epidermal growth factor (EGF), and transforming growth factor β (TGF‐β).