Regulation of p38 mitogen‐activated kinase‐mediated fetal membrane senescence by statins

Ayad, Martina; Taylor, Brandie D.; Menon, Ramkumar

doi:10.1111/aji.12999

Cited by 19 publications

(15 citation statements)

References 54 publications

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“…After isolating 2 distinct cell populations, we further tested responsiveness of these cells to stimulants. We have been using a water-soluble CSE extract that is found to be consistent in producing ROS-associated with OS as is often seen in the intrauterine environment prior to term and preterm labor [41][42][43][44][45][46][47][48]. We have been using CSE as a laboratory reagent to induce OS, and it has been much more effective and reproducible than reagents traditionally used, such as hydrogen peroxide or tumor necrosis factor alpha [45].…”

Section: Chorion Cell Stimulation With Cigarette Smoke Extract (Cse)mentioning

confidence: 99%

Isolation and characterization human chorion membrane trophoblast and mesenchymal cells

et al. 2020

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Section: Chorion Cell Stimulation With Cigarette Smoke Extract (Cse)mentioning

confidence: 99%

Isolation and characterization human chorion membrane trophoblast and mesenchymal cells

et al. 2020

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“…Placental and FM (i.e., amniochorion) tissues from term, not in labor, cesarean deliveries (TNIL) (n 5) were used for this project and prepared as previously described by our laboratory (n 6 tissues for western blotting and n 5 tissues for explant culture) (Ayad et al, 2018;Sheller-Miller et al, 2020). Briefly, the FM was dissected from the placenta, washed three times in normal saline, cleaned with sterile saline-moistened gauze to clear any adherent blood clots and all the decidua, and washed in Hank's balanced solution (HBSS) with penicillin 100 U/mL and streptomycin 100 µg/ml.…”

Section: Placental and Fm Explant Culturementioning

confidence: 99%

Organic Anion Transporting Polypeptide 2B1 in Human Fetal Membranes: A Novel Gatekeeper for Drug Transport During Pregnancy?

Ganguly¹,

Kammala²,

Benson³

et al. 2021

Front. Pharmacol.

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Current intervention strategies have not been successful in reducing the risks of adverse pregnancy complications nor maternal and fetal morbidities associated with pregnancy complications. Improving pregnancy and neonatal outcomes requires a better understanding of drug transport mechanisms at the feto-maternal interfaces, specifically the placenta and fetal membrane (FM). The role of several solute carrier uptake transporter proteins (TPs), such as the organic anion transporting polypeptide 2B1 (OATP2B1) in transporting drug across the placenta, is well-established. However, the mechanistic role of FMs in this drug transport has not yet been elucidated. We hypothesize that human FMs express OATP2B1 and functions as an alternate gatekeeper for drug transport at the feto-maternal interface. We determined the expression of OATP2B1 in term, not-in-labor, FM tissues and human FM cells [amnion epithelial cell (AEC), chorion trophoblast cell (CTC), and mesenchymal cells] using western blot analyses and their localization using immunohistochemistry. Changes in OATP2B1 expression was determined for up to 48 h after stimulation with cigarette smoke extract (CSE), an inducer of oxidative stress. The functional role of OATP2B1 was determined by flow cytometry using a zombie violet dye substrate assay. After OATP2B1 gene silencing, its functional relevance in drug transport through the feto-maternal interface was tested using a recently developed feto-maternal interface organ-on-a-chip (OOC) system that contained both FM and maternal decidual cells. Propagation of a drug (Rosuvastatin, that can be transported by OATP2B1) within the feto-maternal interface OOC system was determined by mass spectrometry. FMs express OATP2B1 in the CTC and AEC layers. In FM explants, OATP2B1 expression was not impacted by oxidative stress. Uptake of the zombie violet dye within AECs and CTCs showed OATP2B1 is functionally active. Silencing OATP2B1 in CTCs reduced Rosuvastatin propagation from the decidua to the fetal AEC layer within the feto-maternal interface-OOC model. Our data suggest that TPs in FMs may function as a drug transport system at the feto-maternal interface, a function that was previously thought to be performed exclusively by the placenta. This new knowledge will help improve drug delivery testing during pregnancy and contribute to designing drug delivery strategies to treat adverse pregnancy outcomes.

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“…Culturing fetal membrane tissues or biopsy-based explants obtained from discarded human fetal membrane from scheduled cesarean deliveries are commonly utilized for tissue-level culture and studies (Fortunato et al, 1994;Menon et al, 2011;Menon et al, 2014;Richardson et al, 2017a;Ayad et al, 2018). Additionally, live fetal membrane samples can be mounted into imaging chambers allowing for cellular and collagen visualization over time.…”

Section: Ex Vivo Tissue Culture Techniquesmentioning

confidence: 99%

Organ-On-Chip Technology: The Future of Feto-Maternal Interface Research?

et al. 2020

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Regulation of p38 mitogen‐activated kinase‐mediated fetal membrane senescence by statins

Cited by 19 publications

References 54 publications

Isolation and characterization human chorion membrane trophoblast and mesenchymal cells

Isolation and characterization human chorion membrane trophoblast and mesenchymal cells

Organic Anion Transporting Polypeptide 2B1 in Human Fetal Membranes: A Novel Gatekeeper for Drug Transport During Pregnancy?

Organ-On-Chip Technology: The Future of Feto-Maternal Interface Research?

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