Nature Communications · 2017 · 474 citations · 31 references
MedicineEndocrinologyPhysiologyReproductive BiologyReproductive EndocrinologyReproductive PhysiologyDynamic Culture SystemsMenstrual CycleMicrofluidic DevicesMicrofluidic SystemsMicrofluidicsOvarian PhysiologyDynamic Cell CultureFemale Reproductive EndocrinologyMenstrual Cycle EndocrinologyMenstrual Cycle RegulationMicrofluidic Culture SystemsMicrofluidic PlatformsOrgan-on-chip PlatformsOvarian Follicle Physiology
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.
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