Endocrine Abstracts

Maternal thyroid hormones (THs) are important for fetoplacental development. We have previously reported lower fetal circulating concentration of THs in severe intrauterine growth restriction (IUGR) compared to gestationally-matched normal fetuses. The villous placental expression of TH receptors (TRs) and the TH transporter MCT8 is increased, whilst MCT10 expression is decreased, with severe IUGR.

Objective: To assess the TH responsiveness of human cytotrophoblasts (CTs) from normal and IUGR term placentae.

Methods: CTs were isolated from normal (38–40 weeks; n=9) and IUGR (35–39 weeks; n=5) placentae with local ethical committee approval. T3 uptake by CTs was assessed by [¹²⁵I]-T3 uptake assay. CT viability (MTT assay), apoptosis (Caspase 3/7 activity) and syncytialisation (total HCG secretion) were assessed following T3 treatment for 66 or 90 h.

Results: Mean T3 uptake by CTs from normal and IUGR placentae was 5 and 6% respectively. The viability of CTs from IUGR compared to normal placentae was reduced 20% in the presence of 1 nM T3 (P<0.01), but not in the absence of T3. Apoptosis in CTs from IUGR compared to normal placentae was increased by 20% at 1 nM T3, (not statistically significant). The rise in HCG secretion between 18 and 90 h post-culture was 3–5 fold higher by CTs isolated from IUGR compared to normal placentae, regardless of T3 treatment (P<0.05).

Conclusions: Even though CTs from normal and IUGR human placentae demonstrate similar efficiency of T3 uptake, they show an altered response to T3 treatment that may be partly attributed to increased TR expression in IUGR. Our results are consistent with previous reports of increased apoptosis and syncytialisation in IUGR placentae. Decreased cell viability and increased apoptosis, but not increased syncytialisation, may be partly mediated by altered TH action within the trophoblast of IUGR placentae, which may adversely affect placental development and contribute to the pathogenesis of IUGR.