Activin A and Follistatin in Menstrual Blood: Low Concentrations in Women With Dysfunctional Uterine Bleeding

In: Reproductive Sciences · 2007 · vol. 14(4) , pp. 383–389 · doi:10.1177/1933719107303985 · PMID:17644811 · W2072915076
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Activin A and follistatin are measurable in menstrual blood at higher concentrations than peripheral serum, and these levels are significantly lower in women with dysfunctional uterine bleeding.

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This study measured activin A and follistatin protein concentrations in menstrual and peripheral blood and quantified their endometrial mRNA expression in endometrial samples collected during the perimenstrual period from healthy women with regular cycles (n=15) and women with dysfunctional uterine bleeding (DUB) (n=12). Using highly sensitive enzyme immunoassays and real-time PCR, the authors found that activin A and follistatin were detectable at higher concentrations in menstrual than peripheral serum in controls, but both were significantly lower in the menstrual serum of women with DUB, along with reduced endometrial activin A and follistatin mRNA expression. There was no correlation between menstrual and peripheral serum levels for either protein. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Activin A and follistatin are growth factors produced by several organs, comprising the endometrium, where they modulate cell and tissue differentiation. In this study, the authors tested whether activin A and follistatin are measurable in menstrual blood and whether their concentrations change in women with dysfunctional uterine bleeding (DUB). The authors evaluated healthy women with regular menstrual cycles (n = 15) and women with DUB (n = 12). Activin A and follistatin were measured in both menstrual and peripheral blood samples using highly sensitive enzyme immunoassays, whereas their respective mRNAs were quantified by real-time polymerase chain reaction in endometrial samples collected during the perimenstrual period. Activin A concentrations were 4-fold higher in menstrual than in peripheral serum of healthy women (mean +/- SE, 4.24 +/- 0.18 vs 1.00 +/- 0.15 ng/mL, P < .001) and were significantly lower in women with DUB compared to healthy subjects (P < .001). Follistatin concentration was 8-fold higher in menstrual than in peripheral serum of healthy women (3.94 +/- 0.49 vs 0.49 +/- 0.04 ng/mL, P < .001) and was significantly lower in the menstrual serum of women with DUB compared to controls (P < .001). There was no correlation between menstrual and peripheral serum concentrations of both proteins. The endometrial expression of activin A and follistatin mRNA was lower in women with DUB compared to controls (P < .05). Both activin A and follistatin are measurable in high concentrations in human menstrual blood and are relatively lower in women with DUB. The quantitative assessment of activin A and follistatin in menstrual serum might be a putative clinical marker of endometrial function.
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Abstract

Activin A and follistatin are growth factors produced by several organs, comprising the endometrium, where they modulate cell and tissue differentiation. In this study, the authors tested whether activin A and follistatin are measurable in menstrual blood and whether their concentrations change in women with dysfunctional uterine bleeding (DUB). The authors evaluated healthy women with regular menstrual cycles (n = 15) and women with DUB (n = 12). Activin A and follistatin were measured in both menstrual and peripheral blood samples using highly sensitive enzyme immunoassays, whereas their respective mRNAs were quantified by real-time polymerase chain reaction in endometrial samples collected during the perimenstrual period. Activin A concentrations were 4-fold higher in menstrual than in peripheral serum of healthy women (mean ± SE, 4.24 ± 0.18 vs 1.00 ± 0.15 ng/mL, P < .001) and were significantly lower in women with DUB compared to healthy subjects (P < .001). Follistatin concentration was 8-fold higher in menstrual than in peripheral serum of healthy women (3.94 ± 0.49 vs 0.49 ± 0.04 ng/mL, P < .001) and was significantly lower in the menstrual serum of women with DUB compared to controls (P < .001). There was no correlation between menstrual and peripheral serum concentrations of both proteins. The endometrial expression of activin A and follistatin mRNA was lower in women with DUB compared to controls (P < .05). Both activin A and follistatin are measurable in high concentrations in human menstrual blood and are relatively lower in women with DUB. The quantitative assessment of activin A and follistatin in menstrual serum might be a putative clinical marker of endometrial function. Similar content being viewed by others

References

Fazleabas AT, Strakova Z. Endometrial function: cell specific changes in the uterine environment. Mol Cell Endocrinol. 2002;186:143–147. Vale W, Rivier C, Hsueh A, et al. Chemical and biological characterization of the inhibin family of protein hormones. Recent Prog Horm Res. 1988;44:1–34. Mather JP, Woodruff TK, Krummen LA. Paracrine regulation of reproductive function by inhibin and activin. Proc Soc Exp Biol Med. 1992;201:1–15. Findlay JK. An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis. Biol Reprod. 1993;48:15–23. Woodruff TK. Regulation of cellular and system function by activin. Biochem Pharmacol. 1998;55:953–963. Florio P, Luisi S, Vigano P, et al. Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle. Hum Reprod. 1998;13:2606–2611. Florio P, Severi FM, Luisi S, et al. Endometrial expression and secretion of activin A, but not follistatin, increase in the secretory phase of the menstrual cycle. J Soc Gynecol Investig. 2003;10:237–243. Leung PH, Salamonsen LA, Findlay JK. Immunolocalization of inhibin and activin subunits in human endometrium across the menstrual cycle. Hum Reprod. 1998;13:3469–3477. Jones RL, Salamonsen LA, Critchley HO, Rogers PA, Affandi B, Findlay JK. Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestinonly contraception. Mol Hum Reprod. 2000;6:1107–1117. Jones RL, Salamonsen LA, Findlay JK. Activin A promotes human endometrial stromal cell decidualization in vitro. J Clin Endocrinol Metab. 2002;87:4001–4004. Petraglia F, Florio P, Luisi S, et al. Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab. 1998;83: 1194–1200. Reis FM, Di Blasio AM, Florio P, Ambrosini G, Di Loreto C, Petraglia F. Evidence for local production of inhibin A and activin A in patients with ovarian endometriosis. Fertil Steril. 2001;75:367–373. Shimonaka M, Inouye S, Shimasaki S, Ling N. Follistatin binds to both activin and inhibin through the common subunit. Endocrinology. 1991;128:3313–3315. de Winter JP, ten Dijke P, de Vries CJ, et al. Follistatins neutralize activin bioactivity by inhibition of activin binding to its type II receptors. Mol Cell Endocrinol. 1996;116:105–114. Schneyer AL, Rzucidlo DA, Sluss PM, Crowley WF Jr. Characterization of unique binding kinetics of follistatin and activin or inhibin in serum. Endocrinology. 1994;135:667–674. Phillips DJ, de Kretser DM. Follistatin: a multifunctional regulatory protein. Front Neuroendocrinol. 1998;19:287–322. Jones RL, Salamonsen LA, Zhao YC, Ethier JF, Drummond AE, Findlay JK. Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization. Mol Hum Reprod. 2002;8:363–374. Speroff L, Fritz MA. Dysfunctional uterine bleeding. In: Speroff L, Fritz MA, eds. Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005:547–571. Higham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990;97:734–739. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25. Knight PG, Muttukrishna S, Groome NP. Development and application of a two-site enzyme immunoassay for the determination of “total” activin-A concentrations in serum and follicular fluid. J Endocrinol. 1996;148:267–279. Evans LW, Muttukrishna S, Groome NP. Development, validation and application of an ultra-sensitive two-site enzyme immunoassay for human follistatin. J Endocrinol. 1998;156: 275–282. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–408. Luisi S, Florio P, Reis FM, Petraglia F. Expression and secretion of activin A: possible physiological and clinical implications. Eur J Endocrinol. 2001;145:225–236. Bell SC. The insulin-like growth factor binding proteins— the endometrium and decidua. Ann N Y Acad Sci. 1991; 622:120–137. Psychoyos A. Endocrine control of egg implantation. In: Greep RO, Astwood EG, Geiger SR, eds. Handbook of Physiology. Washington, DC: American Physiological Societty; 1973:87–215. Tierney EP, Giudice LC. Role of activin A as a mediator of in vitro endometrial stromal cell decidualization via the cyclic adenosine monophosphate pathway. Fertil Steril. 2004;81(suppl 1): 899–903. McCarthy SA, Bicknell R. Inhibition of vascular endothelial cell growth by activin-A. J Biol Chem. 1993;268:23066–23071. Kozian DH, Ziche M, Augustin HG. The activin-binding protein follistatin regulates autocrine endothelial cell activity and induces angiogenesis. Lab Invest. 1997;76:267–276. Panopoulou E, Murphy C, Rasmussen H, Bagli E, Rofstad EK, Fotsis T. Activin A suppresses neuroblastoma xenograft tumor growth via antimitotic and antiangiogenic mechanisms. Cancer Res. 2005;65:1877–1886. Jones RL, Salamonsen LA, Findlay JK. Potential roles for endometrial inhibins, activins and follistatin during human embryo implantation and early pregnancy. Trends Endocrinol Metab. 2002;13:144–150. Rombauts L, Donoghue J, Cann L, Jones RL, Healy DL. Activin-A secretion is increased in the eutopic endometrium from women with endometriosis. Aust N Z J Obstet Gynaecol. 2006;46:148–153. Garzia E, Borgato S, Cozzi V, et al. Lack of expression of endometrial prolactin in early implantation failure: a pilot study. Hum Reprod. 2004;19:1911–1916. Francis J, Rai R, Sebire NJ, et al. Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome. Mol Hum Reprod. 2006;12:435–442. Tuckerman E, Laird SM, Stewart R, Wells M, Li TC. Markers of endometrial function in women with unexplained recurrent pregnancy loss: a comparison between morphologically normal and retarded endometrium. Hum Reprod. 2004;19: 196–205. Ulukus M, Cakmak H, Arici A. The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006;13:467–476. Author information Authors and Affiliations Corresponding author Additional information This research was supported by CNPq, Ministry of Science and Technology, Brazil; the Italian Ministry of University and Scientific Research; and the University of Siena, Italy. We thank Irene M. Dias, RN, for her excellent technical assistance. Rights and permissions About this article Cite this article Reis, F.M., Nascimento, L.L., Tsigkou, A. et al. Activin A and Follistatin in Menstrual Blood: Low Concentrations in Women With Dysfunctional Uterine Bleeding. Reprod. Sci. 14, 383–389 (2007). https://doi.org/10.1177/1933719107303985 Published: Issue date: DOI: https://doi.org/10.1177/1933719107303985

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