Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies

Manuel S. Vidal; Lauren S. Richardson; Ananth Kumar Kammala; Sungjin Kim; Po Yi Lam; Rahul Cherukuri; Tilu Jain Thomas; Mohammed Bettayeb; Arum Han; Ivan Rusyn; Ramkumar Menon

doi:10.1039/D3LC00998J

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies†

Manuel S. Vidal, Jr.,

‡^ab Lauren S. Richardson,

‡^b Ananth Kumar Kammala,

^b Sungjin Kim,^c Po Yi Lam,^c Rahul Cherukuri,^c Tilu Jain Thomas,^b Mohammed Bettayeb,^b Arum Han,

^c Ivan Rusyn^d and Ramkumar Menon*^a

Author affiliations

* Corresponding authors

^a Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Texas, USA
E-mail: ra2menon@utmb.edu

^b Department of Biochemistry and Molecular Biology, University of the Philippines Manila, Manila, Philippines

^c Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA

^d Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

Abstract

The effects of endocrine-disrupting compounds (EDCs) on the placenta, a critical gestational organ for xenobiotic protection, are well reported; however, models to determine the role of EDCs in placental disruption are limited. An advanced 2nd-trimester human placenta organ-on-chip model (2TPLA-OOC) was developed and validated, with six representative cells of the maternal and the fetal interface interconnected with microchannels. Various EDCs (150 ng mL⁻¹ each of bisphenol A, bisphenol S, and polybrominated diphenyl ethers-47 and -99) were gradually propagated across the chip for 72 hours, and their various effects were determined. Cigarette smoke extract (CSE), an environmental risk factor, was used as a positive control. EDCs produced overall oxidative stress in the placental/decidual cells, induced cell-specific endocrine effects, caused limited (<10%) apoptosis/necrosis in trophoblasts and mesenchymal cells, induced localized inflammation but an overall anti-inflammatory shift, did not change immune cell migration from stroma to decidua, and did not affect placental nutrient transport. Overall, (1) the humanized 2TPLA-OOC recreated the placental organ and generated data distinct from the trophoblast and other cells studied in isolation, and (2) at doses associated with adverse pregnancies, EDCs produced limited and localized insults, and the whole organ compensated for the exposure.

Lab on a Chip

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies†

Abstract

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Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies

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