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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Methodology

Changes in cell proliferation, but not in vascularisation are characteristic for human endometrium in different reproductive failures - a pilot study

Authors: Ariane Germeyer, Michael von Wolff, Julia Jauckus, Thomas Strowitzki, Tanuj Sharma, Anna T Grazul-Bilska

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

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Abstract

Background

Reproductive failure, determined as recurrent spontaneous abortions (RSA) or recurrent implantation failure (RIF) in women is not well understood. Several factors, including embryo quality, and cellular and molecular changes in endometrium may contribute to the insufficient feto-maternal interaction resulting in reproductive failure. Prior clinical studies suggest an inadequate endometrial growth and development of the endometrium, leading to a lesser endometrial thickness.

Methods

We therefore aimed to determine the cellular proliferation using Ki67, and the expression of markers of vascularisation, such as factor VIII (a marker of endothelial cells) and smooth muscle cell actin (SMCA; a marker of pericytes and smooth muscle cells) in endometrium of healthy women and women with RSA or RIF. LH-dated mid-secretory endometrial biopsies of seven healthy women and twenty women with reproductive failure were examined via immunohistochemistry followed by image analysis.

Results

Cellular proliferation but not expression of factor VIII or SMCA was decreased (P < 0.0004) in endometrium of women with RSA and RIF compared to healthy controls. Conclusion: Our data indicate that reproductive failure is due to insufficient cell proliferation/tissue growth rather than inadequate vascularisation in the endometrium.
Appendix
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Literature
1.
Farquharson RG, Jauniaux E, Exalto N: Updated and revised nomenclature for description of early pregnancy events. Hum Reprod. 2005, 20 (11): 3008-3011. 10.1093/humrep/dei167.CrossRefPubMed
2.
Margalioth EJ, Ben-Chetrit A, Gal M, Eldar-Geva T: Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod. 2006, 21 (12): 3036-3043. 10.1093/humrep/del305.CrossRefPubMed
3.
Li TC, Makris M, Tomsu M, Tuckerman E, Laird S: Recurrent miscarriage: aetiology, management and prognosis. Hum Reprod Update. 2002, 8 (5): 463-481. 10.1093/humupd/8.5.463.CrossRefPubMed
4.
Nyboe Andersen A, Goossens V, Bhattacharya S, Ferraretti AP, Kupka MS, de Mouzon J, Nygren KG: Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE: ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2009, 24 (6): 1267-1287. 10.1093/humrep/dep035.CrossRefPubMed
5.
Christiansen OB, Nielsen HS, Kolte AM: Inflammation and miscarriage. Semin Fetal Neonatal Med. 2006, 11 (5): 302-308. 10.1016/j.siny.2006.03.001.CrossRefPubMed
6.
Potdar N, Konje JC: The endocrinological basis of recurrent miscarriages. Curr Opin Obstet Gynecol. 2005, 17 (4): 424-428. 10.1097/01.gco.0000175363.20094.bd.CrossRefPubMed
7.
Tomassetti C, Meuleman C, Pexsters A, Mihalyi A, Kyama C, Simsa P, D'Hooghe TM: Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?. Reprod Biomed Online. 2006, 13 (1): 58-64. 10.1016/S1472-6483(10)62016-0.CrossRefPubMed
8.
Savaris RF, Hamilton AE, Lessey BA, Giudice LC: Endometrial gene expression in early pregnancy: lessons from human ectopic pregnancy. Reprod Sci. 2008, 15 (8): 797-816. 10.1177/1933719108317585.PubMedCentralCrossRefPubMed
9.
Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC: Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003, 144 (7): 2870-2881. 10.1210/en.2003-0043.CrossRefPubMed
10.
Koler M, Achache H, Tsafrir A, Smith Y, Revel A, Reich R: Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure. Hum Reprod. 2009, 24 (10): 2541-2548. 10.1093/humrep/dep193.CrossRefPubMed
11.
Lee J, Oh J, Choi E, Park I, Han C, Kim do H, Choi BC, Kim JW, Cho C: Differentially expressed genes implicated in unexplained recurrent spontaneous abortion. Int J Biochem Cell Biol. 2007, 39 (12): 2265-2277. 10.1016/j.biocel.2007.06.012.CrossRefPubMed
12.
Tapia A, Gangi LM, Zegers-Hochschild F, Balmaceda J, Pommer R, Trejo L, Pacheco IM, Salvatierra AM, Henriquez S, Quezada M, Vargas M, Ríos M, Munroe DJ, Croxatto HB, Velasquez L: Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy. Hum Reprod. 2008, 23 (2): 340-351. 10.1093/humrep/dem319.CrossRefPubMed
13.
Bagchi MK, Mantena SR, Kannan A, Bagchi IC: Control of uterine cell proliferation and differentiation by C/EBPbeta: functional implications for establishment of early pregnancy. Cell Cycle. 2006, 5 (9): 922-925. 10.4161/cc.5.9.2712.CrossRefPubMed
14.
Barnea ER: Embryo maternal dialogue: From pregnancy recognition to proliferation control. Early Pregnancy. 2001, 5 (1): 65-66.PubMed
15.
Maruyama T, Yoshimura Y: Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium. Endocr J. 2008, 55 (5): 795-810. 10.1507/endocrj.K08E-067.CrossRefPubMed
16.
17.
Fanchin R: Assessing uterine receptivity in 2001: ultrasonographic glances at the new millennium. Ann N Y Acad Sci. 2001, 943: 185-202. 10.1111/j.1749-6632.2001.tb03802.x.CrossRefPubMed
18.
Jirous J, Diejomaoh ME, Al-Abdulhadi F, Boland MH, Nazar M: A comparison of the uterine and intraovarian arterial flows in nonpregnant women having a history of recurrent spontaneous miscarriage associated with antiphospholipid syndrome. Arch Gynecol Obstet. 2004, 270 (2): 74-78. 10.1007/s00404-003-0510-0.CrossRefPubMed
19.
Lisman BA, Boer K, Bleker OP, van Wely M, van Groningen K, Exalto N: Abnormal development of the vasculosyncytial membrane in early pregnancy failure. Fertil Steril. 2004, 82 (3): 654-660. 10.1016/j.fertnstert.2004.02.119.CrossRefPubMed
20.
Murray MJ, Meyer WR, Zaino RJ, Lessey BA, Novotny DB, Ireland K, Zeng D, Fritz MA: A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril. 2004, 81 (5): 1333-1343. 10.1016/j.fertnstert.2003.11.030.CrossRefPubMed
21.
Grazul-Bilska AT, Banerjee J, Yazici I, Borowczyk E, Bilski JJ, Sharma RK, Siemionov M, Falcone T: Morphology and function of cryopreserved whole ovine ovaries after heterotopic autotransplantation. Reprod Biol Endocrinol. 2008, 6: 16-10.1186/1477-7827-6-16.PubMedCentralCrossRefPubMed
22.
Grazul-Bilska AT, Caton JS, Arndt W, Burchill K, Thorson C, Borowczyk E, Bilski JJ, Redmer DA, Reynolds LP, Vonnahme KA: Cellular proliferation and vascularization in ovine fetal ovaries: effects of undernutrition and selenium in maternal diet. Reproduction. 2009, 137 (4): 699-707. 10.1530/REP-08-0375.CrossRefPubMed
23.
Grazul-Bilska AT, Navanukraw C, Johnson ML, Vonnahme KA, Ford SP, Reynolds LP, Redmer DA: Vascularity and expression of angiogenic factors in bovine dominant follicles of the first follicular wave. J Anim Sci. 2007, 85 (8): 1914-1922. 10.2527/jas.2007-0044.CrossRefPubMed
24.
Kirk R, Experimental Design: Procedures for the Behavioral Sciences. 1982, Pacific Grove, CA, USA: Brooks/Cole, 2
25.
Rai R, Regan L: Recurrent miscarriage. Lancet. 2006, 368 (9535): 601-611. 10.1016/S0140-6736(06)69204-0.CrossRefPubMed
26.
Jauniaux E, Burton GJ: Pathophysiology of histological changes in early pregnancy loss. Placenta. 2005, 26 (23): 114-123. 10.1016/j.placenta.2004.05.011.CrossRefPubMed
27.
Strowitzki T, Germeyer A, Popovici R, von Wolff M: The human endometrium as a fertility-determining factor. Hum Reprod Update. 2006, 12 (5): 617-630. 10.1093/humupd/dml033.CrossRefPubMed
28.
Tantbirojn P, Crum CP, Parast MM: Pathophysiology of placenta creta: the role of decidua and extravillous trophoblast. Placenta. 2008, 29 (7): 639-645. 10.1016/j.placenta.2008.04.008.CrossRefPubMed
29.
Mitselou A, Ioachim E, Kitsou E, Vougiouklakis T, Zagorianakou N, Makrydimas G, Stefanaki S, Agnantis NJ: Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium. In Vivo. 2003, 17 (5): 469-477.PubMed
30.
Niklaus AL, Aubuchon M, Zapantis G, Li P, Qian H, Isaac B, Kim MY, Adel G, Pollard JW, Santoro NF: Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women. Hum Reprod. 2007, 22 (6): 1778-1788. 10.1093/humrep/dem032.CrossRefPubMed
31.
Hapangama DK, Turner MA, Drury JA, Quenby S, Hart A, Maddick M, Martin-Ruiz C, von Zglinicki T: Sustained replication in endometrium of women with endometriosis occurs without evoking a DNA damage response. Hum Reprod. 2009, 24 (3): 687-696. 10.1093/humrep/den416.CrossRefPubMed
32.
Mertens HJ, Heineman MJ, Evers JL: The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of ovulatory menstrual cycles. Gynecol Obstet Invest. 2002, 53 (4): 224-230. 10.1159/000064569.CrossRefPubMed
33.
Moller B, Rasmussen C, Lindblom B, Olovsson M: Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle. Mol Hum Reprod. 2001, 7 (1): 65-72. 10.1093/molehr/7.1.65.CrossRefPubMed
34.
Smith SK: Angiogenesis, vascular endothelial growth factor and the endometrium. Hum Reprod Update. 1998, 4 (5): 509-519. 10.1093/humupd/4.5.509.CrossRefPubMed
35.
Punyadeera C, Verbost P, Groothuis P: Oestrogen and progestin responses in human endometrium. J Steroid Biochem Mol Biol. 2003, 84 (4): 393-410. 10.1016/S0960-0760(03)00061-X.CrossRefPubMed
36.
Carranza-Lira S, Blanquet J, Tserotas K, Calzada L: Endometrial progesterone and estradiol receptors in patients with recurrent early pregnancy loss of unknown etiology--preliminary report. Med Sci Monit. 2000, 6 (4): 759-762.PubMed
37.
Ilesanmi AO, Hawkins DA, Lessey BA: Immunohistochemical markers of uterine receptivity in the human endometrium. Microsc Res Tech. 1993, 25 (3): 208-222. 10.1002/jemt.1070250304.CrossRefPubMed
38.
Raga F, Bonilla-Musoles F, Casan EM, Klein O, Bonilla F: Assessment of endometrial volume by three-dimensional ultrasound prior to embryo transfer: clues to endometrial receptivity. Hum Reprod. 1999, 14 (11): 2851-2854. 10.1093/humrep/14.11.2851.CrossRefPubMed
39.
Zollner U, Zollner KP, Specketer MT, Blissing S, Muller T, Steck T, Dietl J: Endometrial volume as assessed by three-dimensional ultrasound is a predictor of pregnancy outcome after in vitro fertilization and embryo transfer. Fertil Steril. 2003, 80 (6): 1515-1517. 10.1016/j.fertnstert.2003.08.004.CrossRefPubMed
40.
Zaidi J, Campbell S, Pittrof R, Tan SL: Endometrial thickness, morphology, vascular penetration and velocimetry in predicting implantation in an in vitro fertilization program. Ultrasound Obstet Gynecol. 1995, 6 (3): 191-198. 10.1046/j.1469-0705.1995.06030191.x.CrossRefPubMed
41.
Plaisier M, Dennert I, Rost E, Koolwijk P, van Hinsbergh VW, Helmerhorst FM: Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod. 2009, 24 (1): 185-197. 10.1093/humrep/den296.CrossRefPubMed
42.
Gargett CE, Rogers PA: Human endometrial angiogenesis. Reproduction. 2001, 121 (2): 181-186. 10.1530/rep.0.1210181.CrossRefPubMed
43.
Reynolds LP, Grazul-Bilska AT, Redmer DA: Angiogenesis in the female reproductive organs: pathological implications. Int J Exp Pathol. 2002, 83 (4): 151-163. 10.1046/j.1365-2613.2002.00277.x.PubMedCentralCrossRefPubMed
44.
Raine-Fenning NJ, Campbell BK, Kendall NR, Clewes JS, Johnson IR: Endometrial and subendometrial perfusion are impaired in women with unexplained subfertility. Hum Reprod. 2004, 19 (11): 2605-2614. 10.1093/humrep/deh459.CrossRefPubMed
45.
Ng EH, Chan CC, Tang OS, Yeung WS, Ho PC: Factors affecting endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound during IVF treatment. Hum Reprod. 2006, 21 (4): 1062-1069. 10.1093/humrep/dei442.CrossRefPubMed
46.
Ng EH, Chan CC, Tang OS, Yeung WS, Ho PC: The role of endometrial blood flow measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during in vitro fertilization treatment. Eur J Obstet Gynecol Reprod Biol. 2007, 135 (1): 8-16. 10.1016/j.ejogrb.2007.06.006.CrossRefPubMed
Metadata
Title
Changes in cell proliferation, but not in vascularisation are characteristic for human endometrium in different reproductive failures - a pilot study
Authors
Ariane Germeyer
Michael von Wolff
Julia Jauckus
Thomas Strowitzki
Tanuj Sharma
Anna T Grazul-Bilska
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-67

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