Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats' Pregnancy.

Gabriel Gomes Araujo,Rinaldo Rodrigues Dos Passos Junior,Thaigra Sousa Soares,Victor Vitorino Lima,Gustavo Tadeu Volpato,Fernanda Regina Giachini,Rosaline Rocha Lunardi

doi:10.3389/fphys.2021.787369

Gabriel Gomes Araujo, Rinaldo Rodrigues Dos Passos Junior + Show 5 more

Open Access

https://doi.org/10.3389/fphys.2021.787369

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Abstract

Etanercept is a tumor necrosis factor alpha (TNF-α) inhibitor chronically used to treat autoimmune diseases. However, the use of etanercept during pregnancy still needs to be further investigated. The aim of this study is to evaluate the etanercept treatment during pregnancy, analyzing maternal reproductive performance, fetal outcomes, and placental repercussions. Wistar rats (200–250 g) were mated and randomly distributed into two experimental groups: control and etanercept (n = 10 animals/group). Treatments with etanercept (0.8 mg/kg, s.c.), or saline (control group) were carried out on days 0, 6, 12, and 18 of gestation. On the morning of the 21st day of pregnancy, rats were euthanized in a CO2 chamber and submitted to laparotomy to remove the fetuses, placentas, ovaries, and maternal organs. There were no differences between groups in the following parameters: water and food consumption; placental efficiency; reproductive parameters, including number of corpora lutea and implants, reabsorption, and pre- and post-implantation losses. However, etanercept treatment increased liver weight, reduced fetal and placental weight, decreased the placental junction zone, reduced the percentage of normal fetuses, and increased visceral or skeletal fetal abnormalities. Therefore, etanercept resulted in damages more related to fetus and placenta. However, more studies with different doses are required to better predict possible injuries elicited using etanercept during pregnancy.

Highlights

During pregnancy, the maternal environment undergoes many physiological adaptations to enable the presence of the concept in the body, ensuring the immunotolerance to the developing fetus (Hviid et al, 2006)
We investigated Wistar rats submitted to etanercept treatment during pregnancy, to assess maternal reproductive performance and possible fetal and placental alterations
Weight gain was observed over the weeks of gestation in both groups

Summary

Introduction

The maternal environment undergoes many physiological adaptations to enable the presence of the concept in the body, ensuring the immunotolerance to the developing fetus (Hviid et al, 2006). The actions of several cytokines are necessary to help the gestational process and the balance between T helper (Th) 1 cytokine profile toward the Th2 profile is crucial to a successful pregnancy (Sykes et al, 2012). A pro-inflammatory environment is required during implantation and parturition (Chaouat, 2013). Tumor necrosis factor alpha (TNF-α), a Th1 cytokine, is one of the earliest and most potent mediators of the inflammatory response (Oliveira et al, 2011). Th1 cytokines including TNF-α are required for vasculogenesis during implantation (Demir et al, 2010). Several obstetric disorders, including recurrent miscarriage, early and severe preeclampsia, diabetes and recurrent implantation failure syndrome, can be originated from

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