title: A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Xiao
authors.affiliation: The Charles Stark Draper Laboratory, Cambridge, Massachusetts 02139, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Coppeta
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Rogers
authors.affiliation: The Charles Stark Draper Laboratory, Cambridge, Massachusetts 02139, USA.
authors.forename: Brett C
authors.initials: BC
authors.lastname: Isenberg
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Olalekan
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: McKinnon
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Danijela
authors.initials: D
authors.lastname: Dokic
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Rashedi
authors.affiliation: Ligand Assay and Analysis Core, Center for Research in Reproduction, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haisenleder
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Malpani
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Chanel A
authors.initials: CA
authors.lastname: Arnold-Murray
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Kuanwei
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Monica M
authors.identifier: 0000-0001-7840-4695
authors.initials: MM
authors.lastname: Laronda
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Kruti P
authors.initials: KP
authors.lastname: Maniar
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.affiliation: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Avram
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Sefton
authors.affiliation: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Spiro
authors.initials: S
authors.lastname: Getsios
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Burdette
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: The Charles Stark Draper Laboratory, Cambridge, Massachusetts 02139, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Borenstein
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008597:Menstrual Cycle; D000090204:Mesothelin; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D010053:Ovary / Q000378:metabolism*; D011247:Pregnancy; D046509:Tissue Culture Techniques / Q000295:instrumentation*