Placental leukocyte infiltration accompannies gestational changes induced by hyperthyroidism

NEIRA, FLAVIA JUDITH; VIRUEL, LUCIANA BELÉN; MORENO-SOSA, TAMARA; GERMANÓ, MARÍA JOSÉ; TRONCOSO, MARIANA; SOAJE, MARTA; VALDEZ, SUSANA RUTH; MACKERN-OBERTI, JUAN PABLO; SÁNCHEZ, MARÍA BELÉN; MICHEL LARA, MARÍA CECILIA; PIETROBON, ELISA OLIVIA; JAHN, GRACIELA ALMA

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2022 vol. 165 p. 235 - 248

1470-1626

The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetaldevelopment. This study suggests an immunological role of thyroid hormones in gestation.Abstract: Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal?fetal interface that causereproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroidhormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It iswell known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism(hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throwlight on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a dailys.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19)and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Westernblot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increasesthe fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higherserum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes wereaccompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, anincreased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitroassays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulatesimmunological and morphological placental aspects and induces fetal phenotypic changes, which could be related topreterm labor observed in hyper.