Effects of soy isoflavonoids (genistein and daidzein) on endometrial receptivity

Document Type : Original Article

Authors

1 Kafkas University, Faculty of Medicine, Department of Histology and Embryology, Kars

2 Alanya Alaaddin Keykubat University, Faculty of Medicine, Department of Histology and Embryology, Antalya

3 Ataturk University, Faculty of Medicine, Department of Histology and Embryology, Erzurum

4 Ataturk University, Faculty of Pharmacy, Department of Pharmacology, Erzurum

5 Agrı Ibrahim Cecen University, Faculty of Pharmacy, Department of biochemistry, Ağrı

6 Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum

Abstract

Objective(s): This study aimed to examine the effects of genistein and daidzein on endometrial receptivity by histopathological, immunohistochemical, and biochemical techniques.
Materials and Methods: In this study, 72 female Sprague-Dawley rats were randomly divided into 8 groups. The endometrial receptivity model was applied to identified groups. Experimental animals were given periorally 10 mg/kg and high 40 mg/kg doses of genistein and daidzein for 5 days by gavage. At the end of the experiment, uterine tissues were evaluated histopathologically, immunohistochemically, and biochemically.
Results: When histopathological findings were examined, significant decreases in pinopod formation were observed in high dose genistein and daidzein groups. When compared with the endometrial receptivity group, immunohistochemical staining findings showed a significant decrease in the expression of integrin β3, integrin αvβ3, LIF, and HOXA10 and an increase in MUC 1 expression in the high dose of genistein and daidzein groups.  In biochemical evaluations, it was determined that genistein and daidzein increased estrogen levels and decreased progesterone levels in a dose-dependent manner.  
Conclusion: Genistein and daidzein have a negative effect on endometrial receptivity.  Therefore, individuals with a risk of infertility should pay attention to the consumption of genistein and daidzein.

Keywords

References

1. Dilara Nilüfer DB. Soya ve Soya Ürünlerinin Fonksiyonel Gıda Bileşenleri. Dergipark 2008; 33:241-250.
2. Dalu A, Haskell JF, Coward L, Lamartiniere CA. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate. Prostate 1998; 37:36-43.
3. Wei HC, Bowen R, Cai QY, Barnes S, Wang Y. Anti-oxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 1995; 208:124-130.
4. Kar PK, Tandon V, Saha NN. Anthelmintic efficacy of genistein, the active principle of Flemingia vestita (Fabaceae): Alterations in the free amino acid pool and ammonia levels in the fluke, Fasciolopsis buski. Parasitol Int 2004; 53:287-291.
5. Cooke PS, Selvaraj V, Yellayi S. Genistein, estrogen receptors, and the acquired immune response. J Nutr 2006; 136:704-708.
6. Casanova M, You L, Gaido KW, Archibeque-Engle S, Janszen DB, Heck HD. Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro. Toxicol Sci 1999; 51:236-244.
7. Okazaki K, Okazaki S, Nakamura H, Kitamura Y, Hatayama K, Wakabayashi S, et al. A repeated 28-day oral dose toxicity study of genistein in rats, based on the ‘Enhanced OECD Test Guideline 407’ for screening endocrine-disrupting chemicals. ArchToxicol 2002; 76:553-559.
8. Medigovic I, Ristic N, Trifunovic S, Manojlovic-Stojanoski M, Milosevic V, Zikic D, et al. Genistein affects ovarian folliculogenesis: A stereological study. Microsc Res Tech 2012; 75:1691-1699.
9. Rice S, Mason HD, Whitehead SA. Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol 2006; 101:216-225.
10. Antón AG, Velasco JAG. Unexplained Infertility: Springer; 2015.
11. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Rev Obstet Gynecol 2008; 1:69-76.
12. Akpak YK, Cekmez Y, Erdogan Cakir A, Karaca N, Batmaz G, Gulsen S, et al. An animal model of effects of nicotine exposure on endometrial receptivity and embryo implantation in pregnancy. J Matern Fetal Neonatal Med 2017; 30:2818-2823.
13. Young SL. Oestrogen and progesterone action on endometrium: A translational approach to understanding endometrial receptivity. Reprod Biomed Online 2013; 27:497-505.
14. Voipio HM, Nevalainen T. Improved method for vaginal plug detection in rats. Scand J Lab Anim Sci 1998; 25:5-9.
15. Aksak Karamese S, Toktay E, Unal D, Selli J, Karamese M, Malkoc I. The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue. Acta Histochem 2015; 117:790-797.
16. Cadirci E, Halici Z, Yayla M, Toktay E, Bayir Y, Karakus E, et al. Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats. Peptides 2016; 82:35-43.
17. Meyerholz DK, Beck AP, Goeken JA, Leidinger MR, Ofori‑Amanfo GK, Brown HC, et al. Glycogen depletion can increase the specifcity of mucin detection in airway tissues. BMC Res Notes 2018; 11:763.
18. Choudhury KR, Yagle KJ, Swanson PE, Krohn KA, Rajendran JG. A robust automated measure of average antibody staining in immunohistochemistry images. J Histochem Cytochem  2010; 58:95-107.
19. Klein M, Vignaud JM, Hennequin V, Toussaint B, Bresler L, Plenat F, et al. Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab 2001; 86:656-658.
20. Bentin-Ley U. Relevance of endometrial pinopodes for human blastocyst implantation. Hum Reprod 2000; 15:67-73.
21. Zhao Y, Chen X, Liu X, Ding Y, Gao R, Qiu Y, et al. Exposure of mice to benzo(a)pyrene impairs endometrial receptivity and reduces the number of implantation sites during early pregnancy. Food Chem Toxicol 2014; 69:244-251.
22. de Ziegler D, Fondop JJ, Le Gal F, Liberek C, Jauch T, Stalberg A. The hormonal control of endometrial receptivity. Proceedings of the 13th World Congress on In Vitro Fertilization, Assisted Reproduction & Genetics 2005:461-471.
23. Wu ZL, Yang Y, Chen Y, Xia GL, Zhang RQ. Effects of subcutaneous administration of daidzein on blastocyst implantation in rats. Food Chem Toxicol 2005; 43:167-172.
24. de Ziegler D, Fanchin R, de Moustier B, Bulletti C. The hormonal control of endometrial receptivity: estrogen (E2) and progesterone. J Reprod Immunol 1998; 39:149-166.
25. Kawakita S, Marotta F, Naito Y, Gumaste U, Jain S, Tsuchiya J, et al. Effect of an isoflavones-containing red clover preparation and alkaline supplementation on bone metabolism in ovariectomized rats. Clin Interv Aging 2009; 4:91-100.
26. Zhong RH, Xie SW, Li GT, Yang WJ, Guo XJ, Li Z, et al. Hormone-like activities of Kuntai capsule in the uteri of ovariectomized rats and immature rabbits. J Tradit Chin Med 2018; 38:853-861.
27. Lu LJW, Anderson KE, Grady JJ, Kohen F, Nagamani M. Decreased ovarian hormones during a soya diet: Implications for breast cancer prevention. Cancer Res 2000; 60:4112-4121.
28. Yelian FD, Yang Y, Hirata JD, Schultz JF, Armant DR. Molecular-interactions between fibronectin and integrins during mouse blastocyst outgrowth. Mol Reprod Dev 1995; 41:435-448.
29. Akpak YK, Cekmez Y, Cakir AE, Karaca N, Batmaz G, Gulsen S, et al. An animal model of effects of nicotine exposure on endometrial receptivity and embryo implantation in pregnancy. J Matern Fetal Neonatal Med 2017; 30:2818-2823.
30. Cekmez Y, Korkmaz V, Cakir A, Gocmen A, Ergun Y, Gulsen S, et al. Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates? J Matern Fetal  Neonatal Med 2016; 29:2703-2706.
31. Tei C, Maruyama T, Kuji N, Miyazaki T, Mikami M, Yoshimura Y. Reduced expression of alpha v beta 3 integrin in the endometrium of unexplained infertility patients with recurrent IVF-ET failures: Improvement by danazol treatment. J Assist Reprod Genet 2003; 20:13-20.
32. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Human Reprod Update 2006; 12:731-746.
33. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, et al. Blastocyst implantation depends on maternal expression of leukemia inhibitory factor. Nature 1992; 359:76-79.
34. Smith SK, Charnock-Jones DS, Sharkey AM. The role of leukaemia inhibitory factor and interleukin-6 in human reproduction. Human Reprod 1998; 13:237-243.
35. Cullinan EB, Abbondanzo SJ, Anderson PS, Pollard JW, Lessey BA, Stewart CL. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine paracrine function in regulating embryo implantation. Proc Natl Acad Sci U S A 1996; 93:3115-3120.
36. Lim HJ, Ma L, Ma WG, Mass RL, Dey SK. Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse. Mol Endocrinol 1999; 13:1005-1017.
37. Hey NA, Graham RA, Seif MW, Aplin JD. The polymorphic epithelial mucin Muc1 in human endometrium is regulated with maximal expression in the implantation phase. J Clin Endocrinol Metab 1994; 78:337-342.
38. Surveyor GA, Gendler SJ, Pemberton L, Das SK, Chakraborty I, Julian J, et al. Expression and steroid hormonal-control of Muc-1 in the mouse uterus. Endocrinol 1995; 136:3639-3647.
39. Horne AW, White JO, Lalani EN, Mobberley MA, Margara RA, Trew GH, et al. Analysis of epitopes on endometrial epithelium by scanning immunoelectron microscopy. Biochem Biophys Res Commun 2002; 292:102-108.
40. Bowen JA, Bazer FW, Burghardt RC. Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo. Biol Reproduct 1996; 55:1098-1106.
Iranian Journal of Basic Medical Sciences
Volume 23, Issue 12
December 2020
Pages 1603-1609

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