{"paper_id":"fbcf7287-e9a1-4b27-9ba2-800eddb00a8a","body_text":"Abstract\nThe endometrium is a complex tissue that is constantly influenced by ovarian steroid hormones such as estrogen and progesterone during the reproductive period. It undergoes regular cyclical changes in each menstrual cycle, with the exception of early menarche and perimenopausal period when ovulation can be irregular. This chapter provides detailed histomorphologic descriptions of the three phases of the menstrual cycle, namely proliferative, secretory, and menstrual, as well as a discussion on the dating of the endometrium. These changes are observed in the functional layer, sparing the basal layer of the endometrium. This is followed by a discussion about the different techniques for obtaining an endometrial sample, adequacy of tissue, and artifacts that may be encountered. The determination of sample adequacy can be challenging as calling minimal tissue adequate may result in false negative and on the contrary casual calling of inadequate sample may lead to an unnecessary repeat procedure. In menstrual cycle disorders, depending on whether there is continuous estrogen stimulation or estrogen deficiency, the endometrium demonstrates prolonged proliferative activity or atrophic changes, respectively. Anovulatory cycle is normally perceived as continuous proliferative activity even in the secretory phase. However, one should interpret this with caution as the duration of the proliferative phase differs in women. The current knowledge of the molecular alterations and microRNA expression in the endometrium is also described in this chapter.\nAccess this chapter\nTax calculation will be finalised at checkout\nPurchases are for personal use only\nSimilar content being viewed by others\nReferences\nAguilar M, Zhang H, Zhang M et al (2021) Serial genomic analysis of endometrium supports the existence of histologically indistinct endometrial cancer precursors. J Pathol 254(1):20–30. https://doi.org/10.1002/path.5628\nAnderson MC, Robboy SJ, Russell P et al (2002) The normal endometrium. In: Robboy SJ, Anderson MC, Russell P (eds) Pathology of the female reproductive tract. Churchill Livingstone, London, pp 241–265\nBao W, Zhang Y, Li S et al (2019) miR-107-5p promotes tumor proliferation and invasion by targeting estrogen receptor-α in endometrial carcinoma. Oncol Rep 41(3):1575–1585. https://doi.org/10.3892/or.2018.6936\nBedner R, Rzepka-Gorska I (2007) Hysteroscopy with directed biopsy versus dilatation and curettage for the diagnosis of endometrial hyperplasia and cancer in perimenopausal women. Eur J Gynaecol Oncol 28:400–402\nBen-Baruch G, Menczer J, Shalev J et al (1980) Uterine perforation during curettage: perforation rates and postperforation management. Isr J Med Sci 16:821–824\nBurney RO, Hamilton AE, Aghajanova L et al (2009) MicroRNA expression profiling of eutopic secretory endometrium in women with versus without endometriosis. Mol Hum Reprod 15(10):625–631. https://doi.org/10.1093/molehr/gap068\nCampbell S (2013) A short history of sonography in obstetrics and gynaecology. Facts Views Vis Obgyn 5:213–229\nCampo R, Van Belle Y, Rombauts L et al (1999) Office mini-hysteroscopy. Hum Reprod Update 5:73–81. https://doi.org/10.1093/humupd/5.1.73\nChen C, Zhao Y, Yu Y et al (2016) MiR-125b regulates endometrial receptivity by targeting MMP26 in women undergoing IVF-ET with elevated progesterone on HCG priming day. Sci Rep 6:25302. https://doi.org/10.1038/srep25302\nCoutifaris C, Myers ER, Guzick DS et al (2004) Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 82:1264–1272. https://doi.org/10.1016/j.fertnstert.2004.03.069\nDuggan MA, Brashert P, Ostor A et al (2001) The accuracy and interobserver reproducibility of endometrial dating. Pathology 33:292–297. https://doi.org/10.1080/00313020126323\nEmons G, Beckmann MW, Schmidt D et al (2015) New WHO classification of endometrial hyperplasias. Geburtshilfe Frauenheilkd 75:135–136. https://doi.org/10.1055/s-0034-1396256\nEngkvist ME, Stratford EW, Lorenz S et al (2017) Analysis of the miR-34 family functions in breast cancer reveals annotation error of miR-34b. Sci Rep 7(1):9655. https://doi.org/10.1038/s41598-017-10189-1\nGarcia-Alonso L, Handfield LF, Roberts K et al (2021) Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nat Genet 53(12):1698–1711. https://doi.org/10.1038/s41588-021-00972-2\nGibson M, Badger GJ, Byrn F et al (1991) Error in histologic dating of secretory endometrium: variance component analysis. Fertil Steril 56:242–247. https://doi.org/10.1016/s0015-0282(16)54479-3\nGrimes DA (1982) Diagnostic dilation and curettage: a reappraisal. Am J Obstet Gynecol 142:1–6. https://doi.org/10.1016/s0002-9378(16)32276-1\nHong X, Luense LJ, McGinnis LK et al (2008) Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology 149(12):6207–6212. https://doi.org/10.1210/en.2008-0294\nHume L, Edge JC, Tinning H et al (2023) MicroRNAs emerging coordinate with placental mammals alter pathways in endometrial epithelia important for endometrial function. iScience 26(4):106339. https://doi.org/10.1016/j.isci.2023.106339\nIbañez-Perez J, Díaz-Nuñez M, Clos-García M et al (2022) microRNA-based signatures obtained from endometrial fluid identify implantative endometrium. Hum Reprod 37(10):2375–2391. https://doi.org/10.1093/humrep/deac184\nJohannisson E, Landgren BM, Rohr HP et al (1987) Endometrial morphology and peripheral hormone levels in women with regular menstrual cycles. Fertil Steril 1987(48):401–408. https://doi.org/10.1016/S0015-0282(16)59406-0\nJones GE (1949) Some newer aspects of the management of infertility. J Am Med Assoc 141:1123–1129, illust. https://doi.org/10.1001/jama.1949.02910160013004\nKammerer U, Rieger L, Kapp M et al (2003) Immunocompetent cells in the endometrium of fetuses and children. Hum Reprod 18:969–975. https://doi.org/10.1093/humrep/deg223\nKarlsson B, Granberg S, Wikland M et al (1995) Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding – a Nordic multicenter study. Am J Obstet Gynecol 172:1488–1494. https://doi.org/10.1016/0002-9378(95)90483-2\nKitaya K, Yamaguchi T, Yasuo T et al (2007) Post-ovulatory rise of endometrial CD16(−) natural killer cells: in situ proliferation of residual cells or selective recruitment from circulating peripheral blood? J Reprod Immunol 76:45–53. https://doi.org/10.1016/j.jri.2007.03.010\nKolanska K, Bendifallah S, Canlorbe G et al (2021) Role of miRNAs in normal endometrium and in endometrial disorders: comprehensive review. J Clin Med 10(16):3457. https://doi.org/10.3390/jcm10163457\nKoonings PP, Moyer DL, Grimes DA (1990) A randomized clinical trial comparing Pipelle and Tis-u-trap for endometrial biopsy. Obstet Gynecol 75:293–295. https://doi.org/10.1016/0020-7292(90)90378-x\nKozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRBase: from microRNA sequences to function. Nucleic Acids Res 47(D1):D155–D162. https://doi.org/10.1093/nar/gky1141\nKumar V, Soni UK, Maurya VK et al (2017) Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation. Sci Rep 7:1885. https://doi.org/10.1038/s41598-017-01764-7\nKuokkanen S, Chen B, Ojalvo L et al (2010) Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium. Biol Reprod 82(4):791–801. https://doi.org/10.1095/biolreprod.109.081059\nLac V, Nazeran TM, Tessier-Cloutier B et al (2019) Oncogenic mutations in histologically normal endometrium: the new normal? J Pathol 249(2):173–181. https://doi.org/10.1002/path.5314\nLamon S, Le Carré J, Petito G et al (2023) The effect of the menstrual cycle on the circulating microRNA pool in human plasma: a pilot study. Hum Reprod 38(1):46–56. https://doi.org/10.1093/humrep/deac243\nLee SK, Kim CJ, Kim DJ et al (2015) Immune cells in the female reproductive tract. Immune Netw 15:16–26. https://doi.org/10.4110/in.2015.15.1.16\nLerner HM (1984) Lack of efficacy of prehysterectomy curettage as a diagnostic procedure. Am J Obstet Gynecol 148:1055–1056. https://doi.org/10.1016/s0002-9378(84)90443-5\nLi R, Qiao J, Wang L et al (2011) MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration. Reprod Biol Endocrinol 9:29. https://doi.org/10.1186/1477-7827-9-29\nLiu W, Niu Z, Li Q et al (2016) MicroRNA and embryo implantation. Am J Reprod Immunol 75:263–271. https://doi.org/10.1111/aji.12470\nManaster I, Mandelboim O (2010) The unique properties of uterine NK cells. Am J Reprod Immunol 63:434–444. https://doi.org/10.1111/j.1600-0897.2009.00794.x\nManganiello PD, Burrows LJ, Dain BJ et al (1998) Vabra aspirator and pipelle endometrial suction curette. A comparison. J Reprod Med 43:889–892\nMcCluggage WG (2006) My approach to the interpretation of endometrial biopsies and curettings. J Clin Pathol 59:801–812. https://doi.org/10.1136/jcp.2005.029702\nMcNeely MJ, Soules MR (1988) The diagnosis of luteal phase deficiency: a critical review. Fertil Steril 1988(50):1–15. https://doi.org/10.1016/s0015-0282(16)59999-3\nMercey O, Popa A, Cavard A et al (2017) Characterizing isomiR variants within the microRNA-34/449 family. FEBS Lett 591(5):693–705. https://doi.org/10.1002/1873-3468.12595\nMoore L, Leongamornlert D, Coorens THH et al (2020) The mutational landscape of normal human endometrial epithelium. Nature 580(7805):640–646. https://doi.org/10.1038/s41586-020-2214-z\nMoradan S, Ghorbani R, Lotfi A (2017) Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding. Saudi Med J 38:497–502. https://doi.org/10.15537/smj.2017.5.19368\nMurray MJ, Meyer WR, Zaino RJ et al (2004) A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 81:1333–1343. https://doi.org/10.1016/j.fertnstert.2003.11.030\nNaim NM, Mahdy ZA, Ahmad S (2007) The Vabra aspirator versus the Pipelle device for outpatient endometrial sampling. Aust N Z J Obstet Gynaecol 47:132–136. https://doi.org/10.1111/j.1479-828X.2007.00699.x\nNaydenov M, Nikolova M, Apostolov A et al (2022) The dynamics of miR-449a/c expression during uterine cycles are associated with endometrial development. Biology (Basel) 12(1):55. https://doi.org/10.3390/biology12010055\nNikas G, Aghajanova L (2002) Endometrial pinopodes: some more understanding on human implantation? Reprod Biomed Online 4(Suppl 3):18–23. https://doi.org/10.1016/s1472-6483(12)60111-4\nNikolova M, Naydenov M, Glogovitis I et al (2021) Coupling miR/isomiR and mRNA expression signatures unveils new molecular layers of endometrial receptivity. Life (Basel) 11(12):1391. https://doi.org/10.3390/life11121391\nNoyes RW, Haman JO (1953) Accuracy of endometrial dating: correlation of endometrial dating with basal body temperature and menses. Fertil Steril 4:504–517. https://doi.org/10.1016/s0015-0282(16)31446-7\nNoyes RW, Hertig AT, Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1:3–25. https://doi.org/10.1016/j.fertnstert.2019.08.079\nPan JL, Yuan DZ, Zhao YB et al (2017) Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells. Acta Physiol (Oxf) 219(3):683–692. https://doi.org/10.1111/apha.12762\nPaulson RJ (2011) Hormonal induction of endometrial receptivity. Fertil Steril 96:530–535. https://doi.org/10.1016/j.fertnstert.2011.07.1097\nPei T, Liu C, Liu T et al (2018) miR-194-3p represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis. Endocrinology 159(7):2554–2562. https://doi.org/10.1210/en.2018-00374\nPerrot-Applanat M, Groyer-Picard MT, Garcia E et al (1988) Immunocytochemical demonstration of estrogen and progesterone receptors in muscle cells of uterine arteries in rabbits and humans. Endocrinology 123:1511–1519. https://doi.org/10.1210/endo-123-3-1511\nPerrot-Applanat M, Ancelin M, Buteau-Lozano H et al (2000) Ovarian steroids in endometrial angiogenesis. Steroids 65:599–603. https://doi.org/10.1016/s0039-128x(00)00117-3\nReed BG, Babayev SN, Chen LX et al (2018) Estrogen-regulated miRNA-27b is altered by bisphenol A in human endometrial stromal cells. Reproduction 156(6):559–567. https://doi.org/10.1530/REP-18-0041\nReijnen C, Visser NCM, Bulten J et al (2017) Diagnostic accuracy of endometrial biopsy in relation to the amount of tissue. J Clin Pathol 70:941–946. https://doi.org/10.1136/jclinpath-2017-204338\nRodriguez GC, Yaqub N, King ME (1993) A comparison of the Pipelle device and the Vabra aspirator as measured by endometrial denudation in hysterectomy specimens: the Pipelle device samples significantly less of the endometrial surface than the Vabra aspirator. Am J Obstet Gynecol 168:55–59. https://doi.org/10.1016/s0002-9378(12)90884-4\nRogers PA, Abberton KM (2003) Endometrial arteriogenesis: vascular smooth muscle cell proliferation and differentiation during the menstrual cycle and changes associated with endometrial bleeding disorders. Microsc Res Tech 60:412–419. https://doi.org/10.1002/jemt.10279\nSakhdari A, Moghaddam PA, Liu Y (2016) Endometrial samples from postmenopausal women: a proposal for adequacy criteria. Int J Gynecol Pathol 35:525–530. https://doi.org/10.1097/PGP.0000000000000279\nStewart CJ, Campbell-Brown M, Critchley HO et al (1999) Endometrial apoptosis in patients with dysfunctional uterine bleeding. Histopathology 34:99–105. https://doi.org/10.1046/j.1365-2559.1999.00599.x\nStock RJ, Kanbour A (1975) Prehysterectomy curettage. Obstet Gynecol 45:537–541\nStrowitzki T, Germeyer A, Popovici R et al (2006) The human endometrium as a fertility-determining factor. Hum Reprod Update 12:617–630. https://doi.org/10.1093/humupd/dml033\nTan GC, Dibb N (2015) IsomiRs have functional importance. Malays J Pathol 37(2):73–81\nTan GC, Chan E, Molnar A et al (2014) 5′ isomiR variation is of functional and evolutionary importance. Nucleic Acids Res 42(14):9424–9435. https://doi.org/10.1093/nar/gku656\nVisser NCM, Reijnen C, Massuger L et al (2017) Accuracy of endometrial sampling in endometrial carcinoma: a systematic review and meta-analysis. Obstet Gynecol 130:803–813. https://doi.org/10.1097/AOG.0000000000002261\nWord B, Gravlee LC, Wideman GL (1958) The fallacy of simple uterine curettage. Obstet Gynecol 12:642–648\nYamaguchi M, Yoshihara K, Suda K et al (2021) Three-dimensional understanding of the morphological complexity of the human uterine endometrium. iScience 24(4):102258. https://doi.org/10.1016/j.isci.2021.102258\nYamaguchi M, Nakaoka H, Suda K et al (2022) Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium. Nat Commun 13(1):943. https://doi.org/10.1038/s41467-022-28568-2\nZaman SS, Mazur MT (1993) Endometrial papillary syncytial change. A nonspecific alteration associated with active breakdown. Am J Clin Pathol 99:741–745. https://doi.org/10.1093/ajcp/99.6.741\nZheng Q, Zhang D, Yang YU et al (2017) MicroRNA-200c impairs uterine receptivity formation by targeting FUT4 and alpha1,3-fucosylation. Cell Death Differ 24:2161–2172. https://doi.org/10.1038/cdd.2017.136\nZhou M, Fu J, Xiao L et al (2016) miR-196a overexpression activates the MEK/ERK signal and represses the progesterone receptor and decidualization in eutopic endometrium from women with endometriosis. Hum Reprod 31(11):2598–2608. https://doi.org/10.1093/humrep/dew223\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEditor information\nEditors and Affiliations\nRights and permissions\nCopyright information\n© 2025 Springer Nature Singapore Pte Ltd.\nAbout this entry\nCite this entry\nTan, G.C., Wong, Y.P., Khong, T.Y. (2025). Menstrual Cycle of Endometrium . In: Zheng, W., Fadare, O., Quick, C.M. (eds) Gynecologic and Obstetric Pathology. Springer, Singapore. https://doi.org/10.1007/978-981-97-4822-8_55\nDownload citation\nDOI: https://doi.org/10.1007/978-981-97-4822-8_55\nPublished:\nPublisher Name: Springer, Singapore\nPrint ISBN: 978-981-97-4821-1\nOnline ISBN: 978-981-97-4822-8\neBook Packages: MedicineReference Module Medicine","source_license":"CC0","license_restricted":false}