Cellular homeostasis, implantation window and unexplained infertility: role of phosphatase and tensin homolog deleted on chromosome 10
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20193038Keywords:
Apoptosis, Cell proliferation, Endometrium, Implantation window, PTEN, Unexplained infertilityAbstract
Background: Balance between endometrial cell proliferation and apoptosis is crucial for successful embryo implantation. PTEN (phosphatase and tensin homolog deleted on chromosome 10), a pro-apoptotic factor, is proposed to be one of the signaling proteins through which estrogen and progesterone act to affect cellular homeostasis. Although reports in literature have suggested role of PTEN in regulating endometrial cell proliferation and apoptosis during window of implantation, its involvement in women with unexplained infertility is not clear. In the present study, we examined expression, cellular distribution and activation status of PTEN, cell proliferation, and apoptosis in midsecretory endometrium from women with unexplained infertility as compared to fertile controls.
Methods: Endometrial biopsies from infertile (n=11) and fertile women (n=22) were used for immunohistochemical evaluation of PTEN, phospho-PTEN and Ki67. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay was performed for detection of apoptotic cells.
Results: Biopsies from infertile women as compared to fertile controls demonstrated statistically significant: i) decrease in nuclear PTEN (P < 0.001), increase in nuclear phospho-PTEN (P < 0.05), increase in nuclear and cytoplasmic phospho-PTEN/PTEN ratio (P < 0.001 and P < 0.05 respectively) in endometrial stroma, ii) increase in cytoplasmic phospho-PTEN (P < 0.001) and phospho-PTEN/PTEN ratio (P < 0.05) in glandular epithelium (GE), iii) increase in Ki67 labeling in GE (P < 0.01) and stroma (P < 0.05) and, iv) decrease in (P < 0.001) apoptosis.
Conclusions: Altered PTEN expression and associated modulation in cellular homeostasis during the implantation window might contribute to mechanism underlying unexplained infertility.
References
Edelmann RJ, Connolly KJ. Psychological aspects of infertility. Br J Med Psychol. 1986;59:209-19.
Kamath MS, Deepti MK. Unexplained infertility: An approach to diagnosis and management. Curr Med Issues. 2016;14:94-100.
Pandian Z, Bhattacharya S, Vale L, Templeton A. In vitro fertilization for unexplained subfertility. Cochrane Database Syst Rev. 2012;4:1-42.
Makker A, Singh MM. Endometrial receptivity in relation to fertility, infertility and antifertility: Clincal assessment using structural, biochemical and molecular markers. Med Res Rev. 2006;26:699-746.
Makker A, Goel MM, Das V, Agarwal A. PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol. 2012;28:175-81.
Antsiferova YS, Sotnikova NY. Apoptosis and endometrial receptivity: Relationship with in vitro fertilization treatment outcome. World J Obstet Gynecol. 2016;5:87-96.
Antsiferova YS, Sotnikova NY, Bogatova IK, Boitsova AV. Changes of apoptosis regulation in the endometrium of infertile women with tubal factor and endometriosis undergoing in vitro fertilization treatment. JBRA Assisted Reproduction. 2014;18:2-6.
Vatansever HS, Lacin S, Ozbilgin MK. Changed Bcl:Bax ratio in endometrium of patients with unexplained infertility. Acta Histochem. 2005;107:345-55.
Mutter GL, Lin MC. Fitzgerald JT, kum JB, Eng C. Changes in endometrial PTEN expression throughout the human menstrual cycle. J Clin Endocrinol Metab. 2000;85:2334-8.
Guzeloglu-Kayisli O, Kayisli UA, AI-Rejjal R, Zheng W, Luleci G, Arici A. Regulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression by estradiol and progesterone in human endometrium. J Clin Endocrinol Metab. 2003;88:5017-26.
Song MS, Samena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nature Review Mol Cell Biol 2012;13:283-296.
Yang Z, Yuan XG, Chen J, Luo SW, Luo ZJ, Lu NH. Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: a novel mechanism of PTEN inactivation. Clin Res Hepatol Gastroenterol. 2013;37:72-9.
Laguë MN, Detmar J, Paquet M, Boyer A, Richards JS, Adamson SL, Boerboom D. Decidual PTEN expression is required for trophoblast invasion in the mouse. Am J Physiol Endocrinol. 2010;299:E936-E945.
Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3-25.
Makker A, Goel MM, Nigam D, Mahdi AA, Das V, Agarwal A, et al. Aberrant Akt activation during implantation window in infertile women with intramural uterine fibroids. Reproductive Sci. 2018;25:1243-53.
El Faham DA, Elnoury MAH, Morsy MI. Has the time come to include low-level laser photobiomodulation as an adjuvant therapy in the treatment of impaired endometrial receptivity? Lasers Med Sci. 2018;33:55-62.
Avellaira C, Villavicencio A, Bacallao K. Expression of molecules associated with tissue homeostasis in secretory endometria from untreated women with polycystic ovary syndrome. Hum Reprod. 2006;21:3116-21.
Jimenez PT, Mendelson CR. The miR-200 family and its targets in implantation and decidualization. Reprod Sci. 2014;21:102A.
Shen LJ, He JL, Yang DH, Ding YB, Chen XM, Geng YQ, et al. Mmu-microRNA-200a overexpression leads to implantation defect by targeting phosphatase and tensin homolog in mouse uterus. Reprod Sci. 2013;20:1518-28.
