Introduction: Hypothyroidism is estimated to affect 3% of pregnant women and has been linked to gestational diabetes mellitus (GDM) and fetal growth restriction. However, the role of the placenta in mediating this process is poorly understood. This study aimed to investigate placental alterations caused by maternal hypothyroidism that may contribute to perturbed glucose homeostasis in pregnancy.
Methods: Hypothyroidism was induced in nulliparous female Sprague-Dawley rats by exposure to 0.02% methimazole in their drinking water for seven days prior to mating and throughout pregnancy. On embryonic day (E) 16, pregnant dams underwent an intraperitoneal glucose tolerance test. Maternal blood was collected three days prior to mating and on E10, E16 and E20 for determination of plasma thyroxine (T4). Animals were culled on E20 for collection of placental tissue. Placentas were separated into the junctional zone (JZ) and labyrinth zone (LZ) and RNA extracted for qPCR analysis. Gene expression of placental factors implicated in GDM will be assessed by qPCR.
Results: Four days into the methimazole treatment, dams had a significant reduction in plasma T4 concentration relative to control animals and this remained significantly reduced throughout pregnancy. The glucose tolerance test indicated that dams were glucose intolerant by E16 and, on E20, there was a significant reduction in fetal weight. While absolute placental weight was unaffected, JZ weight was reduced and the placenta to body weight ratio increased.
Discussion: This study highlights the importance of thyroid hormone homeostasis for maternal glucose control. Given that the placenta secretes several hormones implicated in GDM, this study investigated how thyroid deficiency impacts placental function. Further analysis will investigate thyroid responsive pathways within the JZ and how these relate to production of placental hormones implicated in GDM. Given that fetal growth is impaired in this model, future studies will also characterise long term outcomes in offspring.