Placental leukocyte infiltration accompannies gestational changes induced by hyperthyroidism

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

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2023

1470-1626

Thyroiddysfunctions (TD) lead to metabolic, angiogenic, and developmental alterationsat the maternal-fetal interface that cause reproductive complications. Thyroidhormones (THs) act through their nuclear receptors that interact with othersteroid hormone receptors. Currently, immunological regulation by thyroidstatus has been characterized to a far less extent. It is well known that THsexert regulatory function on immune cells and modulate cytokine expression, buthow hyperthyroidism (hyperT) modulates placental immunological aspects leadingto placental alterations is still unknown. This work aims to throw light on howhyperT modulates immunological and morphological placental aspects. Control andhyperT (induced by a daily subcutaneous injection of T4 0,25 mg/kg) Wistar ratswere mated eight days after starting T4 treatment, and euthanized on days 19(G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flowcytometry, immunohistochemistry, western blot and histological analysis, andamniotic fluid and serum to evaluate hormone levels. We observed that hyperTincreases fetal number and weight, and placental weight on G19. Moreover,hyperT induced an endocrine imbalance with higher serum corticosterone andprolactin levels and changed placental morphology, specifically the basal zoneand decidua. These changes were accompanied by an increased RNA expression ofGR and MCP-1 genes,  an increased RNA andprotein expression of PRL-R long as well as an increase in CD45+ infiltration.Finally, by in vitro assays, we evidenced that TH induced immune cellactivation. In summary, we demonstrated that hyperT modulates immunological andmorphological placental aspects and induces fetal phenotypic changes, whichcould be related to preterm labor observed in hyperT.@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073786111 1 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;}div.WordSection1{page:WordSection1;}