Human fallopian tube-on-a-chip for preclinical testing of non-hormonal contraceptives with living human sperm
Stejskalova, A.; Calderon, K.; Collins, M.; Feitor, J. F.; Ghose, D.; Tang, S.; Gutzeit, O.; Badey, N.; Gulati, A.; Lopez, M. V.; Chou, D. B.; Petrozza, J. C.; Plebani, R.; Junaid, A.; Budnik, B.; Ingber, D. E.
Show abstract
The fallopian tube serves as a sperm reservoir, and it is the site where the oocytes become fertilized. Here, we describe development of an organ-on-a-chip microfluidic model of the fallopian tube (FT Chip) lined by primary human epithelial cells and stromal fibroblasts derived from the FT ampulla. Abundant tissue folds lined by hormone-responsive, epithelial cells resembling those seen in vivo formed on-chip, but not in epithelial organoids cultured in gel cultures. Comparative time-resolved analysis of human sperm versus oocyte-sized microparticles introduced into the epithelial channel in the presence of estradiol revealed that sperm movement was significantly reduced, while the oocyte-sized particles increased, relative to movements in acellular chips. When the non-hormonal contraceptive TDI-11861 was administered to the chip, dose-dependent inhibition of human sperm motility was detected. Thus, this FT Chip may offer a human preclinical tool to study FT physiology and assess the efficacy and mechanism of action of contraceptives.
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