Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014:2014:985478.
doi: 10.1155/2014/985478. Epub 2014 Jan 23.

Modulation of wolframin expression in human placenta during pregnancy: comparison among physiological and pathological states

Angela Lucariello  1 , Angelica Perna  1 , Carmine Sellitto  1 , Alfonso Baldi  2 , Alessandro Iannaccone  3 , Luigi Cobellis  4 , Antonio De Luca  1 , Maria De Falco  5
Affiliations

Modulation of wolframin expression in human placenta during pregnancy: comparison among physiological and pathological states

Angela Lucariello et al. Biomed Res Int. 2014.

Abstract

The WFS1 gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of the WFS1 gene in mice causes progressive β-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) Very high wolframin expression distributed in the cytotrophoblast cells of placental villi from the first trimester voluntary termination of gestation (VTG), 150x; (b) higher magnification showing the very high immunostaining for wolframin localized at perinuclear level in the cytotrophoblast cells from VTG, 640x; (c) moderate wolframin expression in the cytotrophoblast cells and in the stroma of placental villi from loss of pregnancy (LP), 150x; (d) higher magnification showing the moderate wolframin immunopositivity in the cytoplasm of cytotrophoblast cells from LP, 640x; (e) representative negative control of the first trimester VTG, 150x; (f) representative negative control of the third trimester vaginal delivery (VD), 150x. For all the images, C represents cytotrophoblast and S represents syncytiotrophoblast.
Figure 2
Figure 2
(a) Low wolframin expression in the endothelial cells inside placental villi from the third trimester vaginal delivery (VD), 300x; (b) higher magnification showing wolframin immunopositivity localized in the cytotrophoblast cells (arrow) from the VD, 640x; (c) moderate wolframin immunopositivity in the endothelial cells lining blood vessels of placental villi from caesarean section (CS), 300x; (d) higher magnification showing moderate wolframin expression in endothelial cells and in cytotrophoblast cells (arrow) of placental villi from CS, 640x; (e) low expression level of wolframin in the stroma and endothelial cells of the third trimester placental villi from diabetic women, 300x; (f) higher magnification showing low wolframin expression localized almost exclusively in the stroma and endothelial cells of placenta from diabetic women; no immunopositivity was shown in both cytotrophoblast and syncytiotrophoblast.
Figure 3
Figure 3
Intensity staining of wolframin immunopositivity in human placenta during gestation. Wolframin expression level in placental villi from physiological and pathological human placentas during gestation is shown. Vertical lines show S.E.M. VTG: voluntary termination of gestation, LP: loss of pregnancy, VD: vaginal delivery, CS: caesarean section, and DM: third trimester placentas from women with diabetes mellitus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Wolfram DJ, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings: report on four cases. Mayo Clinic Proceedings. 1938;13:715–718.
    1. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome) Nature Genetics. 1998;20(2):143–148. - PubMed
    1. Strom TM, Hörtnagel K, Hofmann S, et al. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Human Molecular Genetics. 1998;7(13):2021–2028. - PubMed
    1. Fonseca SG, Urano F, Weir GC, Gromada J, Burcin M. Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion. Nature Cell Biology. 2012;14:1105–1112. - PMC - PubMed
    1. Cryns K, Sivakumaran TA, Van den Ouweland JMW, et al. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Human Mutation. 2003;22(4):275–287. - PubMed

Publication types