Organs-on-a-chip to understand reproduction

J. Julie Kim

doi:10.1071/RD24144

RESEARCH ARTICLE

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Organs-on-a-chip to understand reproduction

J. Julie Kim ^A ^*

+ Author Affiliations

- Author Affiliations

^A Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, USA.

^* Correspondence to: j-kim4@northwestern.edu

Reproduction, Fertility and Development 37, RD24144 https://doi.org/10.1071/RD24144

Abstract

Organs-on-a-chip technology (OoC) has transformed biomedical research with realistic human organ models for drug testing and disease research. While still in its infancy in reproductive research, OoC holds immense potential. The development and use of OoC platforms specifically for reproductive processes are highlighted here, including a multi-organ platform for studying the female reproductive tract, devices for investigating embryo implantation, and microfluidic systems aimed at improving pre-implantation embryos. These findings emphasize the transformative potential of OoC technology in reproductive biology, advocating for its broader adoption in the field. The potential applications of OoC technology in both human and animal reproduction are vast and significant. By providing detailed and controlled models of reproductive systems, OoC technology is set to transform reproductive health research, steering it towards a more sustainable and ethical future.

Keywords: assisted reproductive technologies, embryo, female reproductive tract, implantation, microphysiological systems, organs-on-a-chip, reproduction.

References

Abbas Y, Oefner CM, Polacheck WJ, Gardner L, Farrell L, Sharkey A, Kamm R, Moffett A, Oyen ML (2017) A microfluidics assay to study invasion of human placental trophoblast cells. Journal of The Royal Society Interface 14, 20170131.
| Crossref | Google Scholar |

Abe H, Yamashita S, Satoh T, Hoshi H (2002) Accumulation of cytoplasmic lipid droplets in bovine embryos and cryotolerance of embryos developed in different culture systems using serum-free or serum-containing media. Molecular Reproduction and Development 61, 57-66.
| Crossref | Google Scholar | PubMed |

Alzamil L, Nikolakopoulou K, Turco MY (2021) Organoid systems to study the human female reproductive tract and pregnancy. Cell Death & Differentiation 28, 35-51.
| Crossref | Google Scholar | PubMed |

Bläuer M, Heinonen PK, Martikainen PM, Tomás E, Ylikomi T (2005) A novel organotypic culture model for normal human endometrium: regulation of epithelial cell proliferation by estradiol and medroxyprogesterone acetate. Human Reproduction 20, 864-871.
| Crossref | Google Scholar | PubMed |

Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H, Amant F, Timmerman D, Tomassetti C, Vanhie A, Meuleman C, Ferrante M, Vankelecom H (2017) Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development 144, 1775-1786.
| Crossref | Google Scholar | PubMed |

Cadena I, Chen A, Arvidson A, Fogg KC (2021) Biomaterial strategies to replicate gynecological tissue. Biomaterials Science 9, 1117-1134.
| Crossref | Google Scholar | PubMed |

Campo H, Murphy A, Yildiz S, Woodruff T, Cervelló I, Kim JJ (2020) Microphysiological Modeling of the Human Endometrium. Tissue Engineering Part A 26, 759-768.
| Crossref | Google Scholar | PubMed |

Campo H, Zha D, Pattarawat P, Colina J, Zhang D, Murphy A, Yoon J, Russo A, Rogers HB, Lee HC, Zhang J, Trotter K, Wagner S, Ingram A, Pavone ME, Dunne SF, Boots CE, Urbanek M, Xiao S, Burdette JE, Woodruff TK, Kim JJ (2023) A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform. Lab on a Chip 23, 4821-4833.
| Crossref | Google Scholar | PubMed |

Childs BG, Durik M, Baker DJ, van Deursen JM (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nature Medicine 21, 1424-1435.
| Crossref | Google Scholar | PubMed |

Eagle H (1959) Amino acid metabolism in mammalian cell cultures. Science 130, 432-437.
| Crossref | Google Scholar | PubMed |

Ealy AD, Wooldridge LK, McCoski SR (2019) BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle. Journal of Animal Science 97, 2555-2568.
| Crossref | Google Scholar | PubMed |

Esteves TC, van Rossem F, Nordhoff V, Schlatt S, Boiani M, Le Gac S (2013) A microfluidic system supports single mouse embryo culture leading to full-term development. RSC Advances 3, 26451-26458.
| Crossref | Google Scholar |

Fitzgerald HC, Schust DJ, Spencer TE (2021) In vitro models of the human endometrium: evolution and application for women’s health. Biology of Reproduction 104, 282-293.
| Crossref | Google Scholar | PubMed |

Gualtieri R, De Gregorio V, Candela A, Travaglione A, Genovese V, Barbato V, Talevi R (2024) In vitro culture of mammalian embryos: is there room for improvement? Cells 13, 996.
| Crossref | Google Scholar |

Heremans R, Jan Z, Timmerman D, Vankelecom H (2021) Organoids of the female reproductive tract: innovative tools to study desired to unwelcome processes. Frontiers in Cell and Developmental Biology 9, 661472.
| Crossref | Google Scholar | PubMed |

Huang W, Hickson LJ, Eirin A, Kirkland JL, Lerman LO (2022) Cellular senescence: the good, the bad and the unknown. Nature Reviews Nephrology 18, 611-627.
| Crossref | Google Scholar | PubMed |

Izadifar Z, Cotton J, Chen S, Horvath V, Stejskalova A, Gulati A, Logrande NT, Budnik B, Shahriar S, Doherty ER, Xie Y, To T, Gilpin SE, Sesay AM, Goyal G, Lebrilla CB, Ingber DE (2024) Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips. Nature Communications 15, 4578.
| Crossref | Google Scholar | PubMed |

Kim MS, Bae CY, Wee G, Han Y-M, Park J-K (2009) A microfluidic in vitro cultivation system for mechanical stimulation of bovine embryos. Electrophoresis 30, 3276-3282.
| Crossref | Google Scholar | PubMed |

Lessey BA, Young SL (2019) What exactly is endometrial receptivity? Fertility and Sterility 111, 611-617.
| Crossref | Google Scholar | PubMed |

Matsuura K, Hayashi N, Kuroda Y, Takiue C, Hirata R, Takenami M, Aoi Y, Yoshioka N, Habara T, Mukaida T, Naruse K (2010) Improved development of mouse and human embryos using a tilting embryo culture system. Reproductive BioMedicine Online 20, 358-364.
| Crossref | Google Scholar | PubMed |

McKiever M, Frey H, Costantine MM (2020) Challenges in conducting clinical research studies in pregnant women. Journal of Pharmacokinetics and Pharmacodynamics 47, 287-293.
| Crossref | Google Scholar | PubMed |

Murphy AR, Campo H, Kim JJ (2022) Strategies for modelling endometrial diseases. Nature Reviews Endocrinology 18, 727-743.
| Crossref | Google Scholar | PubMed |

Park JY, Mani S, Clair G, Olson HM, Paurus VL, Ansong CK, Blundell C, Young R, Kanter J, Gordon S, Yi AY, Mainigi M, Huh DD (2022) A microphysiological model of human trophoblast invasion during implantation. Nature Communications 13, 1252.
| Crossref | Google Scholar | PubMed |

Rawlings TM, Makwana K, Taylor DM, Molè MA, Fishwick KJ, Tryfonos M, Odendaal J, Hawkes A, Zernicka-Goetz M, Hartshorne GM, Brosens JJ, Lucas ES (2021) Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife 10, e69603.
| Crossref | Google Scholar |

Rizos D, Fair T, Papadopoulos S, Boland MP, Lonergan P (2002a) Developmental, qualitative, and ultrastructural differences between ovine and bovine embryos produced in vivo or in vitro. Molecular Reproduction and Development 62, 320-327.
| Crossref | Google Scholar | PubMed |

Rizos D, Ward F, Duffy P, Boland MP, Lonergan P (2002b) Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Molecular Reproduction and Development 61, 234-248.
| Crossref | Google Scholar | PubMed |

Schafer WR, Fischer L, Roth K, Jullig AK, Stuckenschneider JE, Schwartz P, Weimer M, Orlowska-Volk M, Hanjalic-Beck A, Kranz I, Deppert WR, Zahradnik HP (2011) Critical evaluation of human endometrial explants as an ex vivo model system: a molecular approach. Molecular Human Reproduction 17, 255-265.
| Crossref | Google Scholar | PubMed |

Secomandi L, Borghesan M, Velarde M, Demaria M (2022) The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions. Human Reproduction Update 28, 172-189.
| Crossref | Google Scholar | PubMed |

SenNet Consortium (2022) NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nature Aging 2, 1090-1100.
| Crossref | Google Scholar |

Song Y, Fazleabas AT (2021) Endometrial organoids: a rising star for research on endometrial development and associated diseases. Reproductive Sciences 28, 1626-1636.
| Crossref | Google Scholar | PubMed |

Suryadevara V, Hudgins AD, Rajesh A, Pappalardo A, Karpova A, Dey AK, Hertzel A, Agudelo A, Rocha A, Soygur B, Schilling B, Carver CM, Aguayo-Mazzucato C, Baker DJ, Bernlohr DA, Jurk D, Mangarova DB, Quardokus EM, Enninga EAL, Schmidt EL, Chen F, Duncan FE, Cambuli F, Kaur G, Kuchel GA, Lee G, Daldrup-Link HE, Martini H, Phatnani H, Al-Naggar IM, Rahman I, Nie J, Passos JF, Silverstein JC, Campisi J, Wang J, Iwasaki K, Barbosa K, Metis K, Nernekli K, Niedernhofer LJ, Ding L, Wang L, Adams LC, Ruiyang L, Doolittle ML, Teneche MG, Schafer MJ, Xu M, Hajipour M, Boroumand M, Basisty N, Sloan N, Slavov N, Kuksenko O, Robson P, Gomez PT, Vasilikos P, Adams PD, Carapeto P, Zhu Q, Ramasamy R, Perez-Lorenzo R, Fan R, Dong R, Montgomery RR, Shaikh S, Vickovic S, Yin S, Kang S, Suvakov S, Khosla S, Garovic VD, Menon V, Xu Y, Song Y, Suh Y, Dou Z, Neretti N (2024) SenNet recommendations for detecting senescent cells in different tissues. Nature Reviews Molecular Cell Biology 2024.,.
| Crossref | Google Scholar |

Tantengco OAG, Richardson LS, Radnaa E, Kammala AK, Kim S, Medina PMB, Han A, Menon R (2022) Modeling ascending Ureaplasma parvum infection through the female reproductive tract using vagina-cervix-decidua-organ-on-a-chip and feto-maternal interface-organ-on-a-chip. The FASEB Journal 36, e22551.
| Crossref | Google Scholar | PubMed |

Taylor MW (2014) A history of cell culture. In ‘Viruses and man: a history of interactions’. (Ed. MW Taylor) pp. 41–52. (Springer International Publishing: Cham, Switzerland)

Turco MY, Gardner L, Hughes J, Cindrova-Davies T, Gomez MJ, Farrell L, Hollinshead M, Marsh SGE, Brosens JJ, Critchley HO, Simons BD, Hemberger M, Koo B-K, Moffett A, Burton GJ (2017) Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology 19, 568-577.
| Crossref | Google Scholar | PubMed |

Vajta G, Parmegiani L, Machaty Z, Chen WB, Yakovenko S (2021) Back to the future: optimised microwell culture of individual human preimplantation stage embryos. Journal of Assisted Reproduction and Genetics 38, 2563-2574.
| Crossref | Google Scholar | PubMed |

Vasil IK (2008) A history of plant biotechnology: from the Cell Theory of Schleiden and Schwann to biotech crops. Plant Cell Reports 27, 1423-1440.
| Crossref | Google Scholar | PubMed |

Veronesi F, Contartese D, Di Sarno L, Borsari V, Fini M, Giavaresi G (2023) In vitro models of cell senescence: a systematic review on musculoskeletal tissues and cells. International Journal of Molecular Sciences 24, 15617.
| Crossref | Google Scholar |

Viana JH (2022) 2021 statistics of embryo production and transfer in domestic farm animals. Embryo Technology Newsletter 40, 22-40.
| Google Scholar |

Waaijer MEC, Parish WE, Strongitharm BH, van Heemst D, Slagboom PE, de Craen AJM, Sedivy JM, Westendorp RGJ, Gunn DA, Maier AB (2012) The number of p16INK4a positive cells in human skin reflects biological age. Aging Cell 11, 722-725.
| Crossref | Google Scholar | PubMed |

Wiwatpanit T, Murphy AR, Lu Z, Urbanek M, Burdette JE, Woodruff TK, Kim JJ (2020) Scaffold-free endometrial organoids respond to excess androgens associated with polycystic ovarian syndrome. The Journal of Clinical Endocrinology & Metabolism 105, 769-780.
| Crossref | Google Scholar |

Wu M, Tang W, Chen Y, Xue L, Dai J, Li Y, Zhu X, Wu C, Xiong J, Zhang J, Wu T, Zhou S, Chen D, Sun C, Yu J, Li H, Guo Y, Huang Y, Zhu Q, Wei S, Zhou Z, Wu M, Li Y, Xiang T, Qiao H, Wang S (2024) Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1. Nature Aging 4, 527-545.
| Crossref | Google Scholar | PubMed |

Xiao S, Coppeta JR, Rogers HB, Isenberg BC, Zhu J, Olalekan SA, Mckinnon KE, Dokic D, Rashedi AS, Haisenleder DJ, Malpani SS, Arnold-Murray CA, Chen K, Jiang M, Bai L, Nguyen CT, Zhang J, Laronda MM, Hope TJ, Maniar KP, Pavone ME, Avram MJ, Sefton EC, Getsios S, Burdette JE, Kim JJ, Borenstein JT, Woodruff TK (2017) A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nature Communications 8, 14584.
| Crossref | Google Scholar | PubMed |

Zaniker EJ, Hashim PH, Gauthier S, Ankrum JA, Campo H, Duncan FE (2024) 3D-printed agarose micromold supports scaffold-free mouse ex vivo follicle growth, ovulation, and luteinization. Bioengineering 11, 719.
| Crossref | Google Scholar |