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      Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives

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          Abstract

          Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.

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          Most cited references92

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          Prevalence of Obesity Among Adults and Youth: United States, 2015-2016.

          Obesity is associated with serious health risks. Monitoring obesity prevalence is relevant for public health programs that focus on reducing or preventing obesity. Between 2003–2004 and 2013–2014, there were no significant changes in childhood obesity prevalence, but adults showed an increasing trend. This report provides the most recent national estimates from 2015–2016 on obesity prevalence by sex, age, and race and Hispanic origin, and overall estimates from 1999–2000 through 2015–2016.
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            PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.

            It has been proposed that the Xenopus homeobox gene, XlHbox8, is involved in endodermal differentiation during pancreatic and duodenal development (Wright, C.V.E., Schnegelsberg, P. and De Robertis, E.M. (1988). Development 105, 787-794). To test this hypothesis directly, gene targeting was used to make two different null mutations in the mouse XlHbox8 homolog, pdx-1. In the first, the second pdx-1 exon, including the homeobox, was replaced by a neomycin resistance cassette. In the second, a lacZ reporter was fused in-frame with the N terminus of PDX-1, replacing most of the homeodomain. Neonatal pdx-1 -/- mice are apancreatic, in confirmation of previous reports (Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Nature 371, 606-609). However, the pancreatic buds do form in homozygous mutants, and the dorsal bud undergoes limited proliferation and outgrowth to form a small, irregularly branched, ductular tree. This outgrowth does not contain insulin or amylase-positive cells, but glucagon-expressing cells are found. The rostral duodenum shows a local absence of the normal columnar epithelial lining, villi, and Brunner's glands, which are replaced by a GLUT2-positive cuboidal epithelium resembling the bile duct lining. Just distal of the abnormal epithelium, the numbers of enteroendocrine cells in the villi are greatly reduced. The PDX-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels. These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors.
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              Placental hormones and the control of maternal metabolism and fetal growth.

              To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth. In addition to promoting growth of maternal tissues, placental growth hormone (GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression. The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                16 April 2020
                April 2020
                : 9
                : 4
                : 1142
                Affiliations
                [1 ]Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 33 Polna St, 60-535 Poznan, Poland; 75094@ 123456student.ump.edu.pl (R.S.); pawelgutaj@ 123456ump.edu.pl (P.G.)
                [2 ]Department of Anatomy, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781 Poznan, Poland; mjankowski@ 123456ump.edu.pl (M.J.); bkempisty@ 123456ump.edu.pl (B.K.)
                [3 ]Physiology Graduate Program, North Carolina State University, Campus Box 7608, Raleigh, NC 27695-7608, USA; pemozdzi@ 123456ncsu.edu
                [4 ]Department of Histology and Embryology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781 Poznan, Poland
                [5 ]Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 20 Jihlavská St., 625 00 Brno, Czech Republic
                [6 ]Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
                Author notes
                [* ]Correspondence: ewaozegow@ 123456ump.edu.pl ; Tel.: +61-854-65-55
                Author information
                https://orcid.org/0000-0001-8346-0085
                https://orcid.org/0000-0001-9476-0235
                https://orcid.org/0000-0002-1575-3123
                Article
                jcm-09-01142
                10.3390/jcm9041142
                7230810
                32316284
                5f5ff9a4-9072-41cf-b3b7-746259d7e4aa
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 March 2020
                : 13 April 2020
                Categories
                Review

                diabetes,fetal growth,placental lactogen,obesity
                diabetes, fetal growth, placental lactogen, obesity

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