Abstract
During human pregnancy the placenta produces a variety of proteins like steroid hormones and their receptors that are responsible for the establishment and ongoing of the feto-placental unit. Inhibins are dimeric glycoproteins, composed of an α-subunit and one of two possible β-subunits (β A or β B). Aims of the present study were the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with fetal growth restriction (IUGR). Slides of paraffin embedded placental tissue were obtained after delivery from patients diagnosed with IUGR (n = 6) and normal term placentas (n = 8). Tissue samples were fixed and incubated with monoclonal antibodies inhibin/activin-subunits -α, -β A, -β B. Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score and statistical analysis was performed (P<0.05). A significant lower expression of the inhibin-α subunit in IUGR extravillous trophoblast compared to normal pregnancies was observed, while the inhibin-α immunostaining was significantly upregulated in syncytiotrophoblast. Additionally, a significant down-regulation of inhibin-β B subunit in extravillous trophoblast cells in IUGR syncytiotrophoblast cells was demonstrated. A co-localisation of inhibin-α and the β-subunits was also observed, suggesting a production and secretion of intact inhibin A and inhibin B. Although the precise role of these inhibin/activin subunits in human placenta and IUGR pregnancies is still unclear, they could be involved in autocrine/paracrine signalling, contributing to several aspects like angiogenesis and tissue remodelling.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aitken DA, Wallace EM, Crossley JA, Swanston IA, van Pareren Y, van Maarle M, Groome NP, Macri JN, Connor JM (1996) Dimeric inhibin A as a marker for Downȁ9s syndrome in early pregnancy. N Engl J Med 334:1231–1236
Barker DJP (1998) In utero programming of chronic disease. Clin Sci 95:115–128
Baschat AA (2004) Fetal responses to placental insufficiency: an update. BJOG 111:1031–1041
Bersinger NA, Groome N, Muttukrishna S (2002) Pregnancy-associated and placental proteins in the placental tissue of normal pregnant women and patients with pre-eclampsia at term. Eur J Endocrinol 147:785–793
Bobrow CS, Holmes RP, Muttukrishna S, Mohan A, Groome N, Murphy DJ, Soothill PW (2002) Maternal serum activin A, inhibin A, and follistatin in pregnancies with appropriately grown and small-for-gestational-age fetuses classified by umbilical artery Doppler ultrasound. Am J Obstet Gynecol 186:283–287
Caniggia I, Lye SJ, Cross JC (1997) Activin is a local regulator of human cytotrophoblast cell differentiation. Endocrinology 138:3976–3986
Casagrandi D, Bearfield C, Geary J, Redman CW, Muttukrishna S (2003) Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the placental tissue of patients with pre-eclampsia. Mol Hum Reprod 9:199–203
Dȁ9Antona D, Reis FM, Benedetto C, Evans LW, Groome NP, de Kretser DM, Wallace EM, Petraglia F (2000) Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders. J Endocrinol 165:157–162
de Kretser DM, Hedger MP, Loveland KL, Phillips DJ (2002) Inhibins, activins and follistatin in reproduction. Hum Reprod Update 8:529–541
Debieve F, Beerlandt S, Hubinont C, Thomas K (2000) Gonadotropins, prolactin, inhibin A, inhibin B, and activin A in human fetal serum from midpregnancy and term pregnancy. J Clin Endocrinol Metab 85:270–274
Fang J, Yin W, Smiley E, Wang SQ, Bonadio J (1996) Molecular cloning of the mouse activin beta E subunit gene. Biochem Biophys Res Commun 228:669–674
Florio P, Ciarmela P, Luisi S, Palumbo MA, Lambert-Messerlian G, Severi FM, Petraglia F (2002) Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels. Gynecol Endocrinol 16:365–372
Florio P, Cobellis L, Luisi S, Ciarmela P, Severi FM, Bocchi C, Petraglia F (2001) Changes in inhibins and activin secretion in healthy and pathological pregnancies. Mol Cell Endocrinol 180:123–130
Florio P, Perrone S, Luisi S, Longini M, Tanganelli D, Petraglia F, Buonocore G (2003) Activin A plasma levels at birth: an index of fetal hypoxia in preterm newborn. Pediatr Res 6:6
Greenwood C, Impey L, Muttukrishna S, Groome NP, Redman CW (2001) Intrauterine growth restriction without pre-eclampsia and associated changes in serum inhibin A and activin A levels: a case report. Placenta 22:617–618
Hötten G, Neidhardt H, Schneider C, Pohl J (1995) Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun 206:608–613
Jenkin G, Ward J, Hooper S, Oȁ9Connor A, de Kretser D, Wallace E (2001a) Feto-placental hypoxemia regulates the release of fetal activin A and prostaglandin E(2). Endocrinology 142:963–966
Jenkin G, Ward J, Loose J, Schneider-Kolsky M, Young R, Canny B, Oȁ9Connor A, de Kretser D, Wallace E (2001b) Physiological and regulatory roles of activin A in late pregnancy. Mol Cell Endocrinol 180:131–138
Jeschke U, Richter DU, Hammer A, Briese V, Friese K, Karsten U (2002) Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro. Histochem Cell Biol 117:219–226
Keelan JA, Taylor R, Schellenberg JC, Groome NP, Mitchell MD, North RA (2002) Serum activin A, inhibin A, and follistatin concentrations in preeclampsia or small for gestational age pregnancies. Obstet Gynecol 99:267–274
Lim KH, Zhou Y, Janatpour M, McMaster M, Bass K, Chun SH et al (1997) Human cytotrophoblast differentiation/invasion is abnormal in preeclampsia. Am J Pathol 151:1809–1818
McCarthy SA, Bicknell R (1993) Inhibition of vascular endothelial cell growth by activin-A. J Biol Chem 268:23066–23071
McCluggage WG, Ashe P, McBride H, Maxwell P, Sloan JM (1998) Localization of the cellular expression of inhibin in trophoblastic tissue. Histopathology 32:252–256
Muttukrishna S, Knight PG, Groome NP, Redman CW, Ledger WL (1997) Activin A and inhibin A as possible endocrine markers for pre-eclampsia. Lancet 349:1285–1288
Muttukrishna S, North RA, Morris J, Schellenberg JC, Taylor RS, Asselin J, Ledger W, Groome N, Redman CW (2000) Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia. Hum Reprod 15:1640–1645
Mylonas I, Speer R, Makovitzky J, Richter DU, Briese V, Jeschke U, Friese K (2000) Immunohistochemical analysis of steroid receptors and glycodelin A (PP14) in isolated glandular epithelial cells of normal human endometrium. Histochem Cell Biol 114:405–411
Mylonas I, Jeschke U, Winkler L, Makovitzky J, Richter DU, Briese V, Friese K (2003) Immunohistochemical expression of inhibin-alpha in human endometrium and the in vitro secretion of inhibin, estradiol and cortisol in cultured human endometrial glandular cells. Arch Gynecol Obstet 268:142–150
Mylonas I, Jeschke U, Wiest I, Hoeing A, Vogl J, Shabani N, Kuhn C, Schulze S, Kupka MS, Friese K (2004a) Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle. Histochem Cell Biol 122:461–471
Mylonas I, Makovitzky J, Richter DU, Jeschke U, Briese V, Friese K (2004b) Expression of the inhibin-alpha subunit in normal, hyperplastic and malignant endometrial tissue: an immunohistochemical analysis. Gynecol Oncol 93:92–97
Mylonas I, Makovitzky J, Hoeing A, Richter DU, Vogl J, Schulze S, Jeschke U, Briese V, Friese K (2006) Inhibin/activin subunits beta-A (-βA) and beta-B (-βB) are differentially localized in normal, hyperplastic and malignant human endometrial tissue. Acta Histochem 108:1–11
Petraglia F, Garuti GC, Calza L, Roberts V, Giardino L, Genazzani AR, Vale W, Meunier H (1991) Inhibin subunits in human placenta: localization and messenger ribonucleic acid levels during pregnancy. Am J Obstet Gynecol 165:750–758
Phillips DJ, Jones KL, Scheerlinck JY, Hedger MP, de Kretser DM (2001) Evidence for activin A and follistatin involvement in the systemic inflammatory response. Mol Cell Endocrinol 180:155–162
Schiessl B, Mylonas I, Hantschmann P, Kuhn C, Kunze S, Friese K, Jeschke U (2005) Expression of endothelial NO synthase, inducible NO synthase and estrogen receptors alpha and beta in placental tissue of normal, preeclamptic and intrauterine growth restricted pregnancies. J Histochem Cytochem 53:1441–1449
Tjoa ML, Oudejans CBM, van Vugt JMG, Blankenstein MA, van Wijk IJ (2004) Markers for presymptomatic prediction of preeclampsia and intrauterine growth restriction. Hypertens Pregnancy 23:171–189
Vale W, Rivier C, Hsueh A, Campen C, Meunier H, Bicsak T, Vaughan J, Corrigan A, Bardin W, Sawchenko P et al (1988) Chemical and biological characterization of the inhibin family of protein hormones. Recent Prog Horm Res 44:1–34
Wallace EM, Schneider-Kolsky ME, Edwards A, Baker L, Jenkin G (2003) Maternal serum activin A levels in association with intrauterine fetal growth restriction. BJOG 110:306–310
Welt CK (2002) The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction. Curr Opin Obstet Gynecol 14:317–323
Acknowledgements
We would like to thank the medical doctors of the 1st Department of Obstetrics and Gynaecology—Ludwig-Maximilians-University Munich for obtaining the placental samples. Additionally, we would like to thank Dr. N. Shabani—1st Department of Obsterics and Gynaecology—Ludwig-Maximilians-University Munich for evaluating the placental tissue samples and Dr. U. Bierl—DSL Deutschland GmbH—Sinsheim Germany for his support in conducting this study. This study was financially supported in part by FöFoLe (Nr. 297/03)—Ludwig-Maximilians-University Munich, Munich, Germany and the Weigland Foundation Ludwig-Maximilians-University Munich, Munich, Germany for I. Mylonas.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mylonas, I., Schiessl, B., Jeschke, U. et al. Expression of Inhibin/activin Subunits alpha (-α), beta A (-β A) and beta B (-β B) in Placental Tissue of Normal and Intrauterine Growth Restricted (IUGR) Pregnancies. J Mol Hist 37, 43–52 (2006). https://doi.org/10.1007/s10735-006-9029-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-006-9029-6