Research Article
Decreased glycodelin A expression in rat endometrium after stimulation with recombinant follicle stimulating hormone (rFSH) recombination affects the number of live births
Abstract
Glycodelin A (GdA) has been postulated as a marker of endometrial receptivity. However, its expression pattern following ovarian stimulation is conflicting, and its link with implantation and pregnancy is unknown. This study aimed to evaluate the influence of recombinant follicle stimulating hormone (rFSH) on glycodelin expression levels in the endometrium during the secretory phase and how it interacts with live birth. In the amount of 27 female Wistar rats with regular estrus cycles were separated into normal cycle and two stimulated cycle groups of SC1 & SC2 by injecting rFSH doses of 12 IU and 25 IU, respectively, using intraperitoneally (ip) followed by human chorionic gonadotropin (hCG) injection with a dose of 10 IU 48 h later. First, second, and third days after hCG injection, blood and uterine were obtained. GdA expression was examined by immunohistochemistry, while ELISA measured estrogen and progesterone levels. Male rats were mated with female rats from both groups of normal cycle and stimulated cycle. GdA expression in the glandular epithelium significantly decreased (p < 0.05) between control and dose 2, and between doses 1 and 2. Estrogen and progesterone levels did not differ between normal and stimulated cycles (p > 0.05). Furthermore, there was a significant relationship (p < 0.05) between decreased GdA expression in the glands of the SC1 and SC2 groups and the number of live births (r = 0.68). In conclusion, a significant decrease in GdA expression of 25 IU rFSH group reduced live births from 10 to 4 individuals.
References
- [1] Seppala M, Koistinen H, Koistinen R, Hautala L, Chiu PC, Yeung WS. Glycodelin in reproductive endocrinology and hormone-related cancer. Eur J Endocrinol. 2009; 160(2): 121-133. https://doi.org/10.1530/EJE-08-0756.
- [2] Matorras R, Matorras F, Mendoza R, Rodriguez M, Remohi J, Rodriguez-Escudero FJ, Simon C. The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates. Hum Reprod. 2005; 20(10): 2923-2931. https://doi.org/10.1093/humrep/dei129.
- [3] Gleicher N, Vidali A, Barad DH. Successful treatment of unresponsive thin endometrium. Fertil Steril. 2011; 95(6): 2123.e2113-2127. https://doi.org/10.1016/j.fertnstert.2011.01.143
- [4] Julkunen M, Seppala M, Janne OA. Complete amino acid sequence of human placental protein 14: a progesterone-regulated uterine protein homologous to beta-lactoglobulins. Proc Natl Acad Sci USA. 1988; 85(23): 8845-8849. https://doi.org/10.1073/pnas.85.23.8845
- [5] Salim R, Miel J, Savvas M, Lee C, Jurkovic D. A comparative study of glycodelin concentrations in uterine flushings in women with subseptate uteri, history of unexplained recurrent miscarriage and healthy controls. Eur J Obstet Gynecol Reprod Biol. 2007; 133(1): 76-80. https://doi.org/10.1016/j.ejogrb.2006.09.005
- [6] Seo WS, Jee BC, Moon SY. Expression of endometrial protein markers in infertile women and the association with subsequent in vitro fertilization outcome. Fertil Steril. 2011; 95(8): 2707-2710. https://doi.org/10.1016/j.fertnstert.2011.01.009
- [7] Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002; 143(6): 2119-2138. https://doi.org/10.1210/endo.143.6.8885
- [8] Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med. 2012; 18(12): 1754-1767. https://doi.org/10.1038/nm.3012
- [9] Mylonas I, Jeschke U, Kunert-Keil C, Shabani N, Dian D, Bauerfeind I, Kuhn C, Kupka MS, Friese K. Glycodelin A is expressed differentially in normal human endometrial tissue throughout the menstrual cycle as assessed by immunohistochemistry and in situ hybridization. Fertil Steril. 2006; 86(5): 1488-1497. https://doi.org/10.1016/j.fertnstert.2006.03.062
- [10] Rogenhofer N, Bohlmann MK, Thaler CJ, Friese K, Toth B. Habituelle abortneigung: Evidenzbasierte diagnostik und therapie. Geburtsh Frauenh. 2010; 70(07): 544-552. http://doi.org/10.1055/s-0030-1250064
- [11] Vasquez YM, DeMayo FJ. Role of nuclear receptors in blastocyst implantation. Semin Cell Dev Biol. 2013; 24(10-12): 724-735. https://doi.org/10.1016/j.semcdb.2013.08.004
- [12] Uysal S, Isik AZ, Eris S, Yigit S, Yalcin Y, Ozun Ozbay P. Correlation of endometrial glycodelin expression and pregnancy outcome in cases with polycystic ovary syndrome treated with clomiphene citrate plus metformin: a controlled study. Obstet Gynecol Int. 2015; 2015: 278591. https://doi.org/10.1155/2015/278591
- [13] Stavreus-Evers A, Mandelin E, Koistinen R, Aghajnova L, Hovatta O, Seppälä M. Glycodelin is present in pinopodes of receptive-phase human endometrium and is associated with down-regulation of progesterone receptor B. Fertil Steril. 2006; 85(6): 1803-1811. https://doi.org/10.1016/j.fertnstert.2005.12.018
- [14] Jakubowicz DJ, Essah PA, Seppälä M, Jakubowicz S, Baillargeon JP, Koistinen R, Nestler JE. Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy. J Clin Endocrinol Metab. 2004; 89(2): 833-839. https://doi.org/10.1210/jc.2003-030975
- [15] Jakubowicz DJ, Seppälä M, Jakubowicz S, Rodriguez-Armas O, Rivas-Santiago A, Koistinen H, Koistinen R, Nestler JE. Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2001; 86(3): 1126-1133. https://doi.org/10.1210/jcem.86.3.7295
- [16] Seppälä M, Taylor RN, Koistinen H, Koistinen R, Milgrom E. Glycodelin: A major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation. Endocrine Rev. 2002; 23(4): 401-430. https://doi.org/10.1210/er.2001-0026
- [17] Bastu E, Mutlu MF, Yasa C, Dural O, Nehir Aytan A, Celik C, Buyru F, Yeh J. Role of Mucin 1 and Glycodelin A in recurrent implantation failure. Fertil Steril. 2015; 103(4): 1059-1064.e1052. https://doi.org/10.1016/j.fertnstert.2015.01.025
- [18] Skrzypczak J, Wirstlein P, Mikołajczyk M. Is glycodelin an important marker of endometrial receptivity? Ginekol Pol. 2005; 76(10): 770-781.
- [19] Uchida H, Maruyama T, Nishikawa-Uchida S, Miyazaki K, Masuda H, Yoshimura Y. Glycodelin in reproduction. Reprod Med Biol. 2013; 12(3): 79-84. https://doi.org/10.1007/s12522-013-0144-2
- [20] Kolbl AC, Jeschke U, Dian D, Friese K, Andergassen U. Glycodelin A - a famous lipocalin and its role in breast cancer. Anticancer Res. 2014; 34(3): 1079-1085.
- [21] Lee CL, Lam KKW, Koistinen H, Seppala M, Kurpisz M, Fernandez N, Pang RTK, Yeung WSB, Chiu PCN. Glycodelin-A as a paracrine regulator in early pregnancy. J Reprod Immunol. 2011; 90(1): 29-34. https://doi.org/10.1016/j.jri.2011.04.007
- [22] Li MQ, Jin LP. Ovarian stimulation for in vitro fertilization alters the protein profile expression in endometrial secretion. Int J Clin Exp Pathol. 2013; 6(10): 1964-1971.
- [23] Brown SE, Mandelin E, Oehninger S, Toner JP, Seppala M, Jones HW. Endometrial glycodelin-A expression in the luteal phase of stimulated ovarian cycles. Fertil Steril. 2000; 74(1): 130-133. https://doi.org/10.1016/S0015-0282(00)00586-0
- [24] Diedrich K, Fauser BCJM, Devroey P, Griesinger G, Evian Annual Reproduction Workshop Group. The role of the endometrium and embryo in human implantation. Hum Reprod Update. 2007; 13(4): 365-377. https://doi.org/10.1093/humupd/dmm011
- [25] Dimitriadis E, Stoikos C, Stafford-Bell M, Clark I, Paiva P, Kovacs G, Salamonsen LA. Interleukin-11, IL-11 receptorα and leukemia inhibitory factor are dysregulated in endometrium of infertile women with endometriosis during the implantation window. J Reprod Immunol. 2006; 69(1): 53-64. https://doi.org/10.1016/j.jri.2005.07.004
- [26] Sarno JL, Kliman HJ, Taylor HS. HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes. J Clin Endocrinol Metab. 2005; 90(1): 522-528. https://doi.org/10.1210/jc.2004-0817
- [27] Matsuzaki S, Canis M, Darcha C, Pouly JL, Mage G. HOXA-10 expression in the mid-secretory endometrium of infertile patients with either endometriosis, uterine fibromas or unexplained infertility. Hum Reprod. 2009; 24(12): 3180-3187. https://doi.org/10.1093/humrep/dep306
- [28] Horne AW, Lalani EN, Margara RA, Ryder TA, Mobberley MA, White JO. The expression pattern of MUC1 glycoforms and other biomarkers of endometrial receptivity in fertile and infertile women. Mol Reprod Dev. 2005; 72(2): 216-229. https://doi.org/10.1002/mrd.20307
- [29] Douglas NC, Thornton II MH, Nurudeen SK, Bucur M, Lobo RA, Sauer MV. Differential expression of serum glycodelin and insulin-like growth factor binding protein 1 in early pregnancy. Reprod Sci. 2013; 20(11): 1376-1381. https://doi.org/10.1177/1933719113485290
- [30] Aghajanova L, Hamilton AE, Giudice LC. Uterine receptivity to human embryonic implantation: histology, biomarkers, and transcriptomics. Semin Cell Dev Biol. 2008; 19(2): 204-211. https://doi.org/10.1016/j.semcdb.2007.10.008
- [31] Demir M, Ince O, Ozkan B, Kelekci S, Sutcu R, Yilmaz B. Endometrial flushing αVβ3 integrin, glycodelin and PGF2α levels for evaluating endometrial receptivity in women with polycystic ovary syndrome, myoma uteri and endometrioma. Gynecol Endocrinol. 2017; 33(9): 716-720. https://doi.org/10.1080/09513590.2017.1318276
- [32] Jeong JW, Lee HS, Franco HL, Broaddus RR, Taketo MM, Tsai SY, Lydon JP, DeMayo FJ. β-catenin mediates glandular formation and dysregulation of β-catenin induces hyperplasia formation in the murine uterus. Oncogene. 2009; 28(1): 31-40. https://doi.org/10.1038/onc.2008.363
- [33] van der Gaast MH, Classen-Linke I, Krusche CA, Beier-Hellwig K, Fauser BCJM, Beier HM, Macklon NS. Impact of ovarian stimulation on mid-luteal endometrial tissue and secretion markers of receptivity. Reprod Biomed Online. 2008; 17(4): 553-563. https://doi.org/10.1016/s1472-6483(10)60244-1
- [34] Kolibianakis EM, Zikopoulos K, Smitz J, Camus M, Tournaye H, Van Steirteghem AC, Devroey P. Elevated progesterone at initiation of stimulation is associated with a lower ongoing pregnancy rate after IVF using GnRH antagonists. Hum Reprod. 2004; 19(7): 1525-1529. https://doi.org/10.1093/humrep/deh272
- [35] Mesen TB, Young SL. Progesterone and the luteal phase: A requisite to reproduction. Obstet Gynecol Clin North Am. 2015; 42(1): 135-151. https://doi.org/10.1016/j.ogc.2014.10.003
- [36] Pirtea P, Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril. 2021; 115(3): 546-560. https://doi.org/10.1016/j.fertnstert.2020.12.010
- [37] Mendoza-Rodriguez CA, Merchant-Larios H, Segura-Valdez MdL, Moreno-Mendoza N, Cruz ME, Arteaga-Lopez P, Camacho-Arroyo I, Dominguez R, Cerbon M. Expression of p53 in luminal and glandular epithelium during the growth and regression of rat uterus during the estrous cycle. Mol Reprod Dev. 2002; 61(4): 445-452. https://doi.org/10.1002/mrd.10114
- [38] Sahar N, Birowo P, Kusmardi K, Kristianty D, Rahmaningrum K, Miranda AV, Rasyad A, Prasasty V. Mucin-1 expression in endometrial tissue of Macaca nemestrina during mid-luteal phase after controlled-ovarian hyperstimulation. Biodiversitas J Biol Divers. 2021; 22(4): 1927-1933. https://doi.org/10.13057/biodiv/d220440
There are 38 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences (Other) |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 28, 2025 |
| Published in Issue | Year 2023 Volume: 27 Issue: 6 |