Central Medical Journal of Obstetrics and Gynecology

Editorial *Corresponding author Luis M. Gómez, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Sciences Center, Memphis, TN, USA, Understanding the Effects of Email: [email protected] Submitted: 31 August 2013 Fetuin-A in Pregnancy Accepted: 31 August 2013 Published: 02 September 2013 Luis M. Gómez* Copyright Division of Maternal-Fetal Medicine, University of Tennessee Health Sciences Center, © 2013 Gómez USA OPEN ACCESS fetuin-A has emerged as a provocative molecule which actions in pregnancy have become the subject of research Women who present with preeclampsia are at risk of developing especially since the last decade. Also known as alpha-2 Heremans- metabolic syndrome later in their life [13,14]. Initial attempts Schmid glycoprotein, fetuin-A is a circulating glycoprotein to associate fetuin-A with preeclampsia were reported by produced in increased amounts during fetal life by various Shinagawa and Saitoh who found that fetuin-A was more tissues. Similar fetuin-A concentrations in maternal serum and prevalent among urine of women who developed preeclampsia umbilical cord suggest passive placental transfer of fetuin-A [15]; this association persisted after delivery. Park and during pregnancy [1]. The concentration of fetuin-A in plasma colleagues compared maternal serum proteome in women who decreases soon after delivery [2]. In the adult life, it is actively developed severe preeclampsia (n=8) with normal pregnancies secreted into the blood stream mainly by the [3]. Research (n=5) [16]; among candidate target , fetuin-A was investigating the effects of fetuin-A in pregnancy has emerged noted to be elevated in severe preeclampsia cases. Johnstone after the following concepts: and collaborators determined the expression in highly - Fetuin-A is a natural regulator of insulin action due to women with preeclampsia (n=5) and controls (n=5) [17]; they its inhibitory effect on insulin receptor tyrosine kinase purified invasive trophoblasts obtained from term placentas of activity and autophosphorylation [4,5]. from preeclamptic placentas. However, dissimilar results have - The encoding human fetuin-A resides on the 3q27 beenfound publishedsignificant by increased the group expression of Molvarec of fetuin-A and colleagues in trophoblasts [18]: region of which is a susceptibility locus for impaired glucose tolerance, diabetes mellitus, and trimester in women who developed severe preeclampsia with metabolic syndrome [6-8]. This genetic association has (n=10)they reported and without significantly (n=20) lower hemolysis-elevated levels of fetuin-A liver in enzymes-the third been observed in clinical medicine [9]. low platelets (HELLP) when compared to normotensive Because fetuin-A is a natural inhibitor of insulin receptor controls (n=20). In a subsequent study by the same group [19], activity, several investigators have studied the association of women with preeclampsia without HELLP (n=93) presented results. In a recent small case-control study, researchers from trimester when compared to normotensive controls (n=127). with significantly lower concentrations of fetuin-A in the third Austriafetuin-A investigatedwith the role of during acute pregnancy glucose ingestion with conflicting during standard oral glucose tolerance test on serum fetuin-A levels The investigators attributed these findings in correlation to the obtained early in the third trimester in women with gestational systemic inflammation that is present in preeclampsia (fetuin-A diabetes mellitus (GDM) (n=10) and normal controls (n=10) as aDecreased negative inflammatory endovascular mediator). trophoblast migration is a common [10]. Fetuin-A correlated only with body mass index but neither pathologic feature in preeclampsia [20,21]. Recently, our group hypothesized that, analogous to its action on the insulin receptor, fetuin-A inhibits the receptor tyrosine kinase activity showed significant association with insulin sensitivity or insulin during or after pregnancy. In another case control study from of trophoblast growth factors, and as a consequence impairs and C-peptide levels nor was influenced by glucose tolerance Hungary involving more subjects (pregnant women with GDM, trophoblast growth and invasion potentially leading to adverse n=30; normal healthy pregnant, n=104; and non-pregnant pregnancy outcomes [22]. By treating human primary extravillous controls, n=104), Kalabay and colleagues assessed maternal trophoblasts with increasing concentrations of fetuin-A, we serum levels of fetuin-A and correlated these levels with indirect parameters of maternal insulin resistance (fasting C peptide and Moreover, enhanced invasiveness of extravillous trophoblasts C-peptide/fasting glucose ratio) [11]. They noted that serum resultingnoted that from trophoblast the addition invasion of various was trophoblast significantly growth decreased. factors levels of fetuin-A were higher in women with GDM and correlated was reversed by elevated concentrations of fetuin-A especially with indirect parameters of insulin resistance. in cells treated with insulin growth factor (IGF)-1 and placental The genetic association of fetuin-A with metabolic syndrome growth factor (PlGF). Exposure to increased concentrations of has been correlated clinically in non pregnant adults [6,12]. fetuin-A correlated with a lower expression of tyrosine kinase

Cite this article: Gómez LM (2013) Understanding the Effects of Fetuin-A in Pregnancy. Med J Obstet Gynecol 1(2): 1010. Gómez (2013) Email: [email protected] Central downstream signaling intermediates suggesting that fetuin-A impairs trophoblast cell invasion by inhibiting receptor tyrosine Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes. 2008; 8. Stefan N, Fritsche A, Weikert C, Boeing H, Joost HG, Häring HU, et al. kinase activity of placental growth factors. Interestingly our in 57: 2762-2767. vitro effects were observed with fetuin-A concentrations that 9. Ix JH, Wassel CL, Kanaya AM, Vittinghoff E, Johnson KC, Koster A, et al. correlate clinically with metabolic syndrome [12]. We correlated Fetuin-A and incident diabetes mellitus in older persons. JAMA. 2008; our in vitro 300: 182-188. fetuin-A levels among women with preeclampsia (n=111) and 10. Farhan S, Handisurya A, Todoric J, Tura A, Pacini G, Wagner O, et al. healthy pregnant findings controls with a case (n=95). control Women study: we with compared preeclampsia, serum Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study. Int J Endocrinol. 2012; 2012: 896736. 11. Kalabay L, Cseh K, Pajor A, Baranyi E, Csákány GM, Melczer Z, et afterespecially controlling those for with diabetes, severe obesity disease, and had chronic significant hypertension. elevated al. Correlation of maternal serum fetuin/alpha2-HS-glycoprotein Ourserum data levels suggest of that fetuin-A; increased this differenceconcentrations remained of fetuin-A significant affect concentration with maternal insulin resistance and anthropometric trophoblast cell invasiveness and elevated serum concentrations parameters of neonates in normal pregnancy and gestational diabetes. of fetuin-A correlate with preeclampsia. Eur J Endocrinol. 2002; 147: 243-248. 12. 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Cite this article Gómez LM (2013) Understanding the Effects of Fetuin-A in Pregnancy. Med J Obstet Gynecol 1(2): 1010.

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