Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
Department of Pharmacy, University of Science and Technology Chittagong, Zakir Hossain Road, Foy's Lake, Khulshi, Chittagong, 4202, Bangladesh.
Cell Biol Int. 2019 May;43(5):486-494. doi: 10.1002/cbin.11114. Epub 2019 Mar 12.
Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 μg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRβ-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P < 0.05 when compared to euthyroid and thyroxine-treated hypothyroid rats). In conclusion, downregulated expression of the thyroid hormone related proteins in the uterus at the day of implantation might result in infertility as reported in hypothyroid condition.
甲状腺功能减退症与不孕有关，但导致与不孕相关的甲状腺功能减退症的机制尚未完全阐明。因此，在这项研究中，我们确定了甲状腺功能减退症对与甲状腺激素功能相关的蛋白质在子宫中的表达的影响，这些蛋白质被认为在着床中发挥作用，包括甲状腺激素受体（TR）、促甲状腺激素受体（TSHR）、视黄酸受体（RAR）和细胞外激酶（ERK）。通过给予甲巯咪唑（MMI）将妊娠雌性大鼠制成甲状腺功能减退症。在甲状腺功能减退症诱导后，将大鼠分为对照组（未治疗）和接受甲状腺素皮下注射，剂量分别为 20、40 和 80μg/kg/天，连续 5 天。在第 6 天，即着床日（GD 6），处死大鼠并计算子宫内胚胎着床部位的数量。然后，采集子宫角，通过 Western blot 和实时 PCR 分别鉴定上述蛋白质及其 mRNA 的表达。在未治疗的甲状腺功能减退症妊娠大鼠中，胚胎着床部位的数量与甲状腺功能正常和接受甲状腺素治疗的甲状腺功能减退症大鼠相比减少。同样，未治疗的甲状腺功能减退症大鼠子宫中 TRα-1、TRβ-1、TSHR、ERK1/2 和 RAR 蛋白和 mRNA 的表达也减少（与甲状腺功能正常和甲状腺素治疗的甲状腺功能减退症大鼠相比，P<0.05）。总之，在着床日子宫中甲状腺激素相关蛋白的表达下调可能导致甲状腺功能减退症中报道的不孕。
