Determination of the Effects of Prenatal Remdesivir Exposure on Placenta Morphology, Placental IgG Transfer, and Fetal Growth in a Humanized Mouse Model
Birth Defects Research
; 115(8):867, 2023.
Artículo
en Inglés
| EMBASE | ID: covidwho-20241292
ABSTRACT
Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence E0300201.).
adult; animal experiment; animal model; apoptosis; body weight; conference abstract; drug therapy; female; fetus; fetus death; fetus development; fetus growth; fetus weight; gene expression; genetic transcription; health center; histopathology; immunoglobulin blood level; implantation; inflammation; intravenous drug administration; mouse; mouse model; necrosis; nonhuman; pH; placenta; placenta development; placenta weight; pregnancy; protein expression; protein function; surgery; beta cyclodextrin sulfobutyl ether; endogenous compound; Fc receptor; immunoglobulin G; remdesivir; sodium hydroxide; water
Texto completo:
Disponible
Colección:
Bases de datos de organismos internacionales
Base de datos:
EMBASE
Tipo de estudio:
Estudio experimental
/
Estudio pronóstico
/
Ensayo controlado aleatorizado
Idioma:
Inglés
Revista:
Birth Defects Research
Año:
2023
Tipo del documento:
Artículo
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