Organoids of the Female Reproductive Tract: Innovative Tools to Study Desired to Unwelcome Processes

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 May 7

PMID 33959613

Citations 14

Authors

Ruben Heremans

Ziga Jan

Dirk Timmerman

Hugo Vankelecom

Affiliations

Soon will be listed here.

Abstract

The pelviperineal organs of the female reproductive tract form an essential cornerstone of human procreation. The system comprises the ectodermal external genitalia, the Müllerian upper-vaginal, cervical, endometrial and oviductal derivatives, and the endodermal ovaries. Each of these organs presents with a unique course of biological development as well as of malignant degeneration. For many decades, various preclinical models have been employed to study female reproductive organ (patho-)biology, however, facing important shortcomings of limited expandability, loss of representativeness and inadequate translatability to the clinic. The recent emergence of 3D organoid models has propelled the field forward by generating powerful research tools that replicate healthy as well as diseased human tissues and are amenable to state-of-the-art experimental interventions. Here, we in detail review organoid modeling of the different female reproductive organs from healthy and tumorigenic backgrounds, and project perspectives for both scientists and clinicians.

Citing Articles

Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors.

Rodriguez-Martinez A, Torrejon-Escribano B, Eritja N, Dorca-Arevalo J, Gabaldon C, Sevigny J Histol Histopathol. 2024; 40(2):171-182.

PMID: 38967084 DOI: 10.14670/HH-18-782.

The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models.

Abady M, Jeong J, Kwon H, Assiri A, Cho J, Saadeldin I Front Pharmacol. 2024; 15:1412188.

PMID: 38948466 PMC: 11211546. DOI: 10.3389/fphar.2024.1412188.

Molecular stratification of the human fetal vaginal epithelium by spatial transcriptome analysis.

Ye Z, Jiang P, Zhu Q, Pei Z, Hu Y, Zhao G Acta Biochim Biophys Sin (Shanghai). 2024; 56(10):1521-1536.

PMID: 38666303 PMC: 11612642. DOI: 10.3724/abbs.2024063.

Bioengineering approaches for the endometrial research and application.

Dai W, Liang J, Guo R, Zhao Z, Na Z, Xu D Mater Today Bio. 2024; 26:101045.

PMID: 38600921 PMC: 11004221. DOI: 10.1016/j.mtbio.2024.101045.

Mechanisms of endometrial aging: lessons from natural conceptions and assisted reproductive technology cycles.

Chemerinski A, Garcia de Paredes J, Blackledge K, Douglas N, Morelli S Front Physiol. 2024; 15:1332946.

PMID: 38482194 PMC: 10933110. DOI: 10.3389/fphys.2024.1332946.

References

Snijders M, de Goeij A, Rousch M, Koudstaal J, Bosman F . Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause. J Reprod Fertil. 1992; 94(2):363-71. DOI: 10.1530/jrf.0.0940363. View

Nakamura T, Miyagawa S, Katsu Y, Watanabe H, Mizutani T, Sato T . Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice. Toxicology. 2012; 296(1-3):13-9. DOI: 10.1016/j.tox.2012.02.010. View

Gray C, Bartol F, Tarleton B, Wiley A, Johnson G, Bazer F . Developmental biology of uterine glands. Biol Reprod. 2001; 65(5):1311-23. DOI: 10.1095/biolreprod65.5.1311. View

Aflatoonian R, Tuckerman E, Elliott S, Bruce C, Aflatoonian A, Li T . Menstrual cycle-dependent changes of Toll-like receptors in endometrium. Hum Reprod. 2006; 22(2):586-93. DOI: 10.1093/humrep/del388. View

Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B, Bui B . Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat Cell Biol. 2019; 21(8):1041-1051. DOI: 10.1038/s41556-019-0360-z. View

Wang Y, Yang D, Cogdell D, Hu L, Xue F, Broaddus R . Genomic characterization of gene copy-number aberrations in endometrial carcinoma cell lines derived from endometrioid-type endometrial adenocarcinoma. Technol Cancer Res Treat. 2010; 9(2):179-89. PMC: 5120669. DOI: 10.1177/153303461000900207. View

Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H . Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 2017; 144(10):1775-1786. DOI: 10.1242/dev.148478. View

Henriksen T, Tanbo T, Abyholm T, Oppedal B, Claussen O, Hovig T . Epithelial cells from human fallopian tube in culture. Hum Reprod. 1990; 5(1):25-31. DOI: 10.1093/oxfordjournals.humrep.a137034. View

Raghavan S, Mehta P, Xie Y, Lei Y, Mehta G . Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J Immunother Cancer. 2019; 7(1):190. PMC: 6642605. DOI: 10.1186/s40425-019-0666-1. View

10.

Bokhman J . Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983; 15(1):10-7. DOI: 10.1016/0090-8258(83)90111-7. View

11.

Boonekamp K, Kretzschmar K, Wiener D, Asra P, Derakhshan S, Puschhof J . Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures. Proc Natl Acad Sci U S A. 2019; 116(29):14630-14638. PMC: 6642409. DOI: 10.1073/pnas.1715272116. View

12.

Maru Y, Tanaka N, Itami M, Hippo Y . Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors. Gynecol Oncol. 2019; 154(1):189-198. DOI: 10.1016/j.ygyno.2019.05.005. View

13.

Cabrera S, Llaurado M, Castellvi J, Fernandez Y, Alameda F, Colas E . Generation and characterization of orthotopic murine models for endometrial cancer. Clin Exp Metastasis. 2011; 29(3):217-27. DOI: 10.1007/s10585-011-9444-2. View

14.

White Y, Woods D, Takai Y, Ishihara O, Seki H, Tilly J . Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012; 18(3):413-21. PMC: 3296965. DOI: 10.1038/nm.2669. View

15.

Donnez O, Van Langendonckt A, Defrere S, Colette S, Van Kerk O, Dehoux J . Induction of endometriotic nodules in an experimental baboon model mimicking human deep nodular lesions. Fertil Steril. 2012; 99(3):783-789.e3. DOI: 10.1016/j.fertnstert.2012.10.032. View

16.

Tsuda H, Hashiguchi Y, Nishimura S, Kawamura N, Inoue T, Yamamoto K . Relationship between HPV typing and abnormality of G1 cell cycle regulators in cervical neoplasm. Gynecol Oncol. 2003; 91(3):476-85. DOI: 10.1016/j.ygyno.2003.08.019. View

17.

Yucer N, Holzapfel M, Vogel T, Lenaeus L, Ornelas L, Laury A . Directed Differentiation of Human Induced Pluripotent Stem Cells into Fallopian Tube Epithelium. Sci Rep. 2017; 7(1):10741. PMC: 5587694. DOI: 10.1038/s41598-017-05519-2. View

18.

Esfandiari F, Favaedi R, Heidari-Khoei H, Chitsazian F, Yari S, Piryaei A . Insight into epigenetics of human endometriosis organoids: DNA methylation analysis of HOX genes and their cofactors. Fertil Steril. 2020; 115(1):125-137. DOI: 10.1016/j.fertnstert.2020.08.1398. View

19.

Roper J, Tammela T, Malli Cetinbas N, Akkad A, Roghanian A, Rickelt S . In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol. 2017; 35(6):569-576. PMC: 5462879. DOI: 10.1038/nbt.3836. View

20.

Jones R, Critchley H, Brooks J, Jabbour H, McNeilly A . Localization and temporal expression of prolactin receptor in human endometrium. J Clin Endocrinol Metab. 1998; 83(1):258-62. DOI: 10.1210/jcem.83.1.4506. View