School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
Placenta. 2023 Aug;139:148-158. doi: 10.1016/j.placenta.2023.06.010. Epub 2023 Jun 22.
Hypothyroidism during pregnancy is associated with fetal growth restriction (FGR). FGR is commonly caused by placental insufficiency and yet the role of hypothyroidism in placental regulation of fetal growth is unknown. This study aimed to investigate the effects of maternal hypothyroidism on placental nutrient transporter expression, placental morphology, and placental metabolism.
Hypothyroidism was induced in female Sprague-Dawley rats by adding methimazole (MMI) to drinking water at moderate (MOD, MMI at 0.005% w/v) and severe (SEV, MMI at 0.02% w/v) doses from one week prior to pregnancy and throughout gestation. Maternal and fetal tissues were collected on embryonic day 20 (E20).
Hypothyroidism reduced fetal weight (P<0.001) despite causing fetal hyperglycaemia (P = 0.016). Placental weight was not affected by hypothyroidism however placental efficiency was reduced (P<0.001), as was the junctional zone (JZ):labyrinth zone (LZ) weight ratio (P = 0.005). LZ glycogen content was increased (P = 0.029) and while mRNA expression of glucose transporters was reduced by hypothyroidism, only GLUT1 protein expression was reduced in male LZs. Maternal hypothyroidism reduced mitochondrial content (P = 0.031), particularly in SEV males relative to CON males (P = 0.004). Protein expression of Complex V (P < 0.001) and Complex III (P = 0.002) of the electron transport chain were also reduced in males. Maternal hypothyroidism reduced LZ (P<0.001) and fetal plasma triglycerides (P = 0.019) while fetal free fatty acids and the expression of LZ lipid transporters was not affected.
Overall, maternal hypothyroidism may lead to FGR through reduced maternal T4 availability, changes to placental morphology, altered nutrient transporter expression and sex-specific effects on placental metabolism. Changes to LZ glycogen and triglyceride stores as well as mitochondrial content suggest a metabolic shift from oxidative phosphorylation to anaerobic glycolysis in males. These changes also likely impact fetal substrate availability and therefore fetal growth.
怀孕期间甲状腺功能减退与胎儿生长受限（FGR）有关。FGR 通常由胎盘功能不全引起，但甲状腺功能减退症在胎盘调节胎儿生长中的作用尚不清楚。本研究旨在探讨母体甲状腺功能减退症对胎盘营养转运蛋白表达、胎盘形态和胎盘代谢的影响。
在怀孕前一周和整个妊娠期，通过在饮用水中添加甲巯咪唑（MMI），将雌性 Sprague-Dawley 大鼠诱导为中度（MOD，MMI 为 0.005% w/v）和重度（SEV，MMI 为 0.02% w/v）甲状腺功能减退症。在胚胎第 20 天（E20）收集母体和胎儿组织。
尽管甲状腺功能减退症导致胎儿高血糖（P=0.016），但仍降低了胎儿体重（P<0.001）。甲状腺功能减退症并未影响胎盘重量，但降低了胎盘效率（P<0.001），以及连接区（JZ）：绒毛区（LZ）重量比（P=0.005）。LZ 糖原含量增加（P=0.029），尽管葡萄糖转运蛋白的 mRNA 表达受到甲状腺功能减退症的抑制，但仅在雄性 LZs 中 GLUT1 蛋白表达降低。母体甲状腺功能减退症降低了线粒体含量（P=0.031），特别是在 SEV 雄性相对于 CON 雄性时（P=0.004）。电子传递链的 Complex V（P<0.001）和 Complex III（P=0.002）的蛋白表达也降低了。母体甲状腺功能减退症降低了 LZ（P<0.001）和胎儿血浆甘油三酯（P=0.019），而胎儿游离脂肪酸和 LZ 脂质转运蛋白的表达不受影响。
总的来说，母体甲状腺功能减退症可能通过减少母体 T4 的可利用性、改变胎盘形态、改变营养转运蛋白的表达以及对胎盘代谢的性别特异性影响，导致 FGR。LZ 糖原和甘油三酯储存以及线粒体含量的变化表明，雄性中从氧化磷酸化到无氧糖酵解的代谢转变。这些变化也可能影响胎儿底物的可用性，从而影响胎儿生长。
