TY - JOUR
T1 - 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
AU - Tantengco, Ourlad Alzeus G.
AU - Richardson, Lauren S.
AU - Radnaa, Enkhtuya
AU - Kammala, Ananth Kumar
AU - Kim, Sungjin
AU - Medina, Paul Mark B.
AU - Han, Arum
AU - Menon, Ramkumar
N1 - Funding Information:
Ourlad Alzeus G. Tantengco is an MD‐PhD trainee in the MD‐PhD in Molecular Medicine Program, supported by the Philippine Council for Health Research and Development, Department of Science and Technology, Republic of the Philippines, and administered through the University of the Philippines Manila. This study was supported by 1R01HD100729 (NIH/NICHD) to Dr. Ramkumar Menon and Dr. Arum Han.
Publisher Copyright:
© 2022 Federation of American Societies for Experimental Biology.
PY - 2022/10
Y1 - 2022/10
N2 - Genital mycoplasmas can break the cervical barrier and cause intraamniotic infection and preterm birth. This study developed a six-chamber vagina-cervix-decidua-organ-on-a-chip (VCD-OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD-OOC were characterized by morphology and immunostaining for cell-specific markers. We transferred the media from the decidual cell chamber of the VCD-OOC to decidual cell chamber in feto-maternal interface organ-on-a-chip (FMi-OOC), which contains the fetal membrane layers. An ascending Ureaplasma parvum infection was created in VCD-OOC. U. parvum was monitored for 48 h post-infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending U. parvum infection model of PTB was developed using CD-1 mice. The cell morphology and expression of cell-specific markers in the VCD-OOC mimicked those seen in lower genital tract tissues. U. parvum reached the cervical epithelial cells and decidua within 48 h and did not cause cell death in VCD-OOC or FMi-OOC cells. U. parvum infection promoted minimal inflammation, while the combination of U. parvum and LPS promoted massive inflammation in the VCD-OOC and FMi-OOC cells. In the animal model, U. parvum vaginal inoculation of low-dose U. parvum did not result in PTB, and even a high dose had only some effects on PTB (20%). However, intra-amniotic injection of U. parvum resulted in 67% PTB. We report the colonization of U. parvum in various cell types; however, inconsistent, and low-grade inflammation across multiple cell types suggests poor immunogenicity induced by U. parvum.
AB - Genital mycoplasmas can break the cervical barrier and cause intraamniotic infection and preterm birth. This study developed a six-chamber vagina-cervix-decidua-organ-on-a-chip (VCD-OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD-OOC were characterized by morphology and immunostaining for cell-specific markers. We transferred the media from the decidual cell chamber of the VCD-OOC to decidual cell chamber in feto-maternal interface organ-on-a-chip (FMi-OOC), which contains the fetal membrane layers. An ascending Ureaplasma parvum infection was created in VCD-OOC. U. parvum was monitored for 48 h post-infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending U. parvum infection model of PTB was developed using CD-1 mice. The cell morphology and expression of cell-specific markers in the VCD-OOC mimicked those seen in lower genital tract tissues. U. parvum reached the cervical epithelial cells and decidua within 48 h and did not cause cell death in VCD-OOC or FMi-OOC cells. U. parvum infection promoted minimal inflammation, while the combination of U. parvum and LPS promoted massive inflammation in the VCD-OOC and FMi-OOC cells. In the animal model, U. parvum vaginal inoculation of low-dose U. parvum did not result in PTB, and even a high dose had only some effects on PTB (20%). However, intra-amniotic injection of U. parvum resulted in 67% PTB. We report the colonization of U. parvum in various cell types; however, inconsistent, and low-grade inflammation across multiple cell types suggests poor immunogenicity induced by U. parvum.
KW - Ureaplasma parvum infection of the maternal uterine tract
KW - microfluidics
KW - mycoplasma
KW - organ-on-a-chip
KW - pregnancy
KW - preterm birth
UR - http://www.scopus.com/inward/record.url?scp=85137940881&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137940881&partnerID=8YFLogxK
U2 - 10.1096/fj.202200872R
DO - 10.1096/fj.202200872R
M3 - Article
C2 - 36106554
AN - SCOPUS:85137940881
SN - 0892-6638
VL - 36
JO - FASEB Journal
JF - FASEB Journal
IS - 10
M1 - e22551
ER -