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The Impact of Immunosuppressive Drugs on Human Placental Explants

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Abstract

The use of immunosuppressive drugs guarantees the vitality of the graft and allows gestation in spite of intercurrences such as prematurity and intrauterine growth restriction. However, little is known about the direct effects of immunosuppressive drugs on placental cells. We investigated the effects of immunosuppressive drugs in the chorionic villous explants from human term placentas of healthy gestations. Human placental explants from term gestations (37-39 week gestational age, n = 12) were exposed to cyclosporine A (CSA, 0, 62.5, 125, 1250 ng/mL) or azathioprine (AZA, 0, 5, 10, 100 ng/mL) separately or, in combination for up to 48 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed a significant decrease in the explant metabolic activity between AZA and the control group (24 hours, 100 ng/mL, 48 hours, all concentrations, P <.005). Cyclosporin A (CsA) reduced cell activity when associated with AZA (48 hours, P <.005). Fibrinoid deposits increased in AZA-treated explants alone (5 ng/mL, 48 hours; 10 ng/mL, 24–48 hours; P <.005) or when associated with CsA (10 AZA/125 CsA, P <.05), whereas in CsA treatment alone, there was an augment in syncytial knots (24–48 hours, P <.005). The sFLT1 gene (24 hours, P <.05) and protein (P <.005) expression increased in AZA and CsA-treatments separately or in combination (P <.05). Placental growth factor increased in AZA (24 hours, 10 ng/mL) and CsA (125 ng/mL; P <.05). In conclusion, our data indicate that AZA primarily acts on the villous metabolism, perturbing placental homeostasis. Since these drugs may alter the balance of angiogenic factors in its selection for clinical application, their impact on the behavior of placental villous should be considered.

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Authors and Affiliations

  1. Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. LineuPrestes, 1524, Butantan, São Paulo, 05508, Brazil

    Sara Z. Gomes PhD, Franciele Araujo BSc, Carla L. Bandeira PhD & Estela Bevilacqua PhD

  2. Gynecology and Obstetrics Department, Botucatu Medical School, Sao Paulo State University, Butantan, São Paulo, 05508, Brazil

    Leandro G. Oliveira MD, PhD

  3. Obstetrics and Gynecology Department, University of São Paulo Medical School, São Paulo, Brazil

    Mara S. Hoshida PhD, Marcelo Zugaib MD, PhD & Rossana P. V. Francisco MD, PhD

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  1. Sara Z. Gomes PhD
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Correspondence to Estela Bevilacqua PhD.

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Gomes, S.Z., Araujo, F., Bandeira, C.L. et al. The Impact of Immunosuppressive Drugs on Human Placental Explants. Reprod. Sci. 26, 1225–1234 (2019). https://doi.org/10.1177/1933719118812739

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