Journal of Midwifery & Women’s Health www.jmwh.org Original Review The Fascinating and Complex Role of the Placenta in Pregnancy and Fetal Well-being CEU Gwen Latendresse, CNM, PhD, Sandra Founds, CNM, PhD, FNP-BC Existing evidence implicates the placenta as the origin of some common pregnancy complications. Moreover, some maternal conditions, such as inadequate nutrition, diabetes, and obesity, are known to adversely affect placental function, with subsequent negative impact on the fetus and newborn. The placenta may also contribute to fetal programming with health consequences into adulthood, such as cardiovascular, metabolic, and mental health disorders. There is evidence that altered placental development, specifically impaired trophoblast invasion and spiral artery remodeling in the first trimester, is the origin of preeclampsia. Prenatal care providers who understand the relationships between placental health and maternal-newborn health can better inform and guide women to optimize health early in pregnancy and prior to conception. This article reviews the current understanding of placental function; placental contributions to normal fetal brain development and timing of birth; and impact of maternal nutrition, obesity, and diabetes on the placenta. J Midwifery Womens Health 2015;60:360–370 c 2015 by the American College of Nurse-Midwives. Keywords: fetal origins of adult disease, placenta, pregnancy INTRODUCTION pregnancy complications, such as preeclampsia and preterm The placenta is an amazing organ. Not only does it play birth. Implications for clinical practice are also addressed. avitalroleinthedeliveryofnutrientsandoxygentothe growing fetus, but also it contributes significantly to the hor- monal milieu of both mother and fetus during pregnancy. The PLACENTAL DEVELOPMENT word placenta originates from the Greek word plakoenta, meaning flat, slab-like object. The placenta is variously re- A brief review and overview of placental development dur- garded and dispatched based on cultural, societal, personal, ing pregnancy may assist the reader to better understand or institutional foundations; that is, some are planted un- how the placenta contributes to perinatal outcomes, such as der a tree, some are eaten, some are incinerated, and some preeclampsia and preterm birth (PTB), and how maternal receive ceremonial treatment and burial.1 Readers are re- conditions, such as diabetes and obesity, can negatively im- ferred to the companion article in this issue of the Journal pact placental function. of Midwifery & Women’s Health to learn more about the The fertilized ovum develops into the blastocyst by the contemporary Western trend in the practice of consuming fifth day postconception. The multistructured blastocyst con- one’splacenta(seeTable1).2,3 However, how much do we re- sists of the embryonic inner cell mass; a fluid-filled cavity; ally know about what the placenta does? and the surrounding trophectoderm, which becomes the pla- Prenatal and intrapartum care providers obtain essential centa. The trophectoderm bilayer is comprised of 2 types of knowledge and skills pertinent to the identification and ap- trophoblasts: the cytotrophoblast stem cells, some of which propriate management of placental abnormalities, such as pla- develop into the outermost layer of syncytiotrophoblasts. The centa previa and abruption. Midwives and other intrapartum blastocyst implants within the maternal decidua, and at 10 to care providers also inspect the placenta after the birth to 12 days postconception is encased in a mantle of syncytiotro- 4 ensure that it is intact and appears normal. However, in recent phoblasts (Figure 1). Lacunaearefluid-filledpocketsamong years the depth of knowledge regarding placental function has the syncytiotrophoblasts. These grow and eventually merge to expanded profoundly. Maternity care providers can benefit form the intervillous spaces that later fill with maternal blood. by increasing their awareness of new insights into placental The syncytiotrophoblast layer remains in direct contact with function and contributions to maternal and fetal outcomes. maternal blood throughout pregnancy. Syncytiotrophoblasts 4 This article 1) reviews current understanding of placental produce hormones as well as deliver nutrients to the fetus. development and function, including placental contributions At 12 days postconception, the cytotrophoblasts pro- to normal fetal brain development and stress response system; liferate and penetrate into the lacunar spaces (Figure 1). 2) describes the impact of nutrition, maternal obesity, and Approximately 2 days later, these cells grow laterally to form diabetes on placental function; and 3) explores existing ev- the cytotrophoblastic shell. These first developmental events Ͻ idence regarding the relationships between the placenta and occur in relatively hypoxic conditions ( 15 mm Hg pO2)that favor cell proliferation (multiplication of cells).5 Appropriate oxygen tension is critical to normal processes to establish a Address correspondence to Gwen Latendresse, CNM, PhD, University of healthy placenta and pregnancy. Cytotrophoblasts leaving Utah College of Nursing, 10 South 2000 East, Salt Lake City, UT 84112. the shell differentiate into extravillous trophoblasts (EVTs). E-mail: [email protected] Proliferative EVTs in cell columns anchor the placenta to 360 1526-9523/09/$36.00 doi:10.1111/jmwh.12344 c 2015 by the American College of Nurse-Midwives ✦ The placenta is a major source of steroid and peptide hormones, such as corticotropin-releasing hormone, which orches- trate the timing of birth, and serotonin, which is essential for fetal neurodevelopment. ✦ The origins of preeclampsia can be traced to inadequate trophoblast invasion and spiral artery remodeling in the placenta during the first trimester of pregnancy. ✦ The placenta may contribute to fetal programming for adult cardiovascular, metabolic, and mental health disorders by failing to protect the fetus from glucocorticoid overexposure. the maternal decidua. Endovascular EVTs form plugs in the to the hormonal environment for both mother and the de- maternal spiral arteries, maintaining the relatively hypoxic en- veloping fetus throughout pregnancy.5 This hormonal envi- vironment early in pregnancy. Deeper layers of decidua and ronment contributes to fetal brain development, continuance maternal blood vessels increase the oxygen tension, which of the pregnancy, labor initiation, and maturation of the fetal stimulates invasiveness of the EVTs migrating into maternal stress response via the hypothalamic-pituitary-adrenal (HPA) tissue.6 Interstitial EVTs invade the decidua and inner one- axis.5,15,18–20 third of the maternal myometrium to remodel 100 to 150 spi- ral arteries. The EVT plugs dissipate at 10 to 12 weeks’ ges- Role of Placental Hormones in Fetal Development tation, establishing early uteroplacental circulation and in- and Fetal Programming creased oxygenation. Remodeling continues in the myome- trial portion of maternal vessels until 20 to 22 weeks’ gestation Recent evidence indicates that placental production of to create low-resistance, high-flow funnels providing mater- some substances, such as serotonin, directly or indirectly nal blood to the intervillous spaces (Figure 2).4,7 contributes to fetal neurodevelopment or neuroprotection. The placenta is a vascular organ (Figure 3),8 which is ap- For example, the placenta synthesizes serotonin from its parent to clinicians upon delivery and inspection. The pla- precursor, tryptophan, which is obtained from maternal 21 cental vasculature begins to develop at 5 weeks’ gestation. dietary sources. Normal fetal brain development requires Bloodvesselsformfromvillousmesenchymalcellsunderthe serotonin, a neurotransmitter crucial for fetal forebrain 22 influence of growth factors, such as fibroblast growth fac- neurogenesis and interconnection between neurons. This tor and vascular endothelial growth factor (see Table 2).5,7,9 process begins early in gestation, with increasing concentra- Angiogenesis, the branching outgrowths of vessels, contin- tions of serotonin and serotonin receptors within the fetal ues throughout pregnancy, later forming capillary sprouts and brain. The fetal brain also selectively accumulates placentally loops that become the mature terminal placental villi.10,11 At derived serotonin over time. Data implicate sensitivity of the maternal–fetal interface, trophoblasts remodel maternal the fetal brain to placental serotonin. Disruptions in the spiral arteries. Meanwhile, vasculogenesis and angiogenesis fetal serotonin system are observed in association with an occur within the fetoplacental tissues. increased risk of serotonin-associated mental illness and behavioral abnormalities in offspring. The consequences of PLACENTAL FUNCTION disruption may extend into adulthood.21–23 The placenta plays several essential roles during pregnancy, Another example is the placental production of enzymes such as delivering nutrients to the growing fetus, exchang- that are often precursors to fetal neuroactive steroids syn- 24 ing oxygen and carbon dioxide, and serving as gatekeeper be- thesized in the placenta and the fetal brain. For example, tween the mother and fetus.12 The placenta is both a passive allopregnanolone is a neuroactive steroid known to provide filter and an active participant in these exchanges.13 neuroprotection to the fetus, but it requires placentally pro- Thegatekeeperroleincludesprotectionofthefetus duced 5-alpha reductase for