A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle

Shuo Xiao, Jonathan R. Coppeta, Hunter B. Rogers, Brett C. Isenberg, Jie Zhu, Susan A. Olalekan, Kelly E. McKinnon, Danijela Dokic, Alexandra S. Rashedi, Daniel J. Haisenleder, Saurabh S. Malpani, Chanel A. Arnold-Murray, Kuanwei Chen, Mingyang Jiang, Lu Bai, Catherine T. Nguyen, Jiyang Zhang, Monica M. Laronda, Thomas J. Hope, Kruti P. ManiarMary Ellen Pavone, Michael J. Avram, Elizabeth C. Sefton, Spiro Getsios, Joanna E. Burdette, J. Julie Kim, Jeffrey T. Borenstein, Teresa K. Woodruff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

382 Scopus citations

Abstract

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ-organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies.

Original languageEnglish (US)
Article number14584
JournalNature communications
Volume8
DOIs
StatePublished - Mar 28 2017

Funding

We thank all patients who donated their reproductive tissues through the Gynecological Tissue Library in Northwestern University, A.J. Spencer and J.Q. Santos for assistance with fabrication and testing of microfluidic devices, and R.N. Shah and A. Rutz kindly provided the 3D-printed scaffold for liver microtissue culture. This work was supported by NIEHS/ORWH/UH2ES022920; NCATS/NIEHS/NICHD/ORWH/UH3TR001207; and the NIH Common Fund

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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