Gestational cholestasis induced intrauterine growth restriction through triggering IRE1α-mediated apoptosis of placental trophoblast cells.

Epidemiological and animal experimental studies suggest an association between gestational cholestasis and intrauterine growth restriction (IUGR). Here, we explored the mechanism through which gestational cholestasis induced IUGR. To establish gestational cholestasis model, pregnant mice were subcutaneously injected with 17α-Ethynylestradiol (E2) on gestational day 13 (GD13)-GD17. Some pregnant mice were intraperitoneally injected with 4µ8C on GD13-GD17. The results found that the apoptosis of trophoblast cells was elevated in placentas of mice with gestational cholestasis and in deoxycholic acid (DCA)-treated human trophoblast cell lines and primary mouse trophoblast cells. Correspondingly, the levels of placental cleaved caspase-3 and Bax were increased, while placental Bcl2 level was decreased in mice with gestational cholestasis and in DCA-treated trophoblast cells. Further analysis found that placental IRE1α pathway was activated in mice with gestational cholestasis and in DCA-treated trophoblast cells. Interestingly, 4µ8C, an IRE1α RNase inhibitor, significantly inhibited caspase-3 activity and apoptosis of trophoblast cells in vivo and in vitro. Importantly, 4µ8C rescued gestational cholestasis-induced placental insufficiency and IUGR. Furthermore, a case-control study demonstrated that placental IRE1α and caspase-3 pathways were activated in cholestasis cases. Our results provide evidence that gestational cholestasis induces placental insufficiency and IUGR may be via triggering IRE1α-mediated apoptosis of placental trophoblast cells.

[Hurthle cell thyroid tumor: an analysis of 28 cases].

OBJECTIVE: To explore the clinical features and the combined treatment modality of Hurthle cell thyroid tumor (HCT). METHODS: Twenty-eight cases of HCT treated between 2001 and 2009 were analyzed retrospectively. RESULTS: The age of the patients ranged from 18 to 72 years (with a median of 46.5 years); 22 females and 6 males. The main symptoms were thyroid solitary node or mass (22 cases) and multiple nodule (6 cases), 2 cases with cervical lymph node metastasis. All of the patients underwent surgery, 11 cases with thyroid lobectomy, 11 cases with thyroid lobectomy plus isthmusectomy, 4 cases with subtotal thyroidectomy, and 2 cases with thyroid lobectomy plus isthmusectomy and combined with modified radical cervical lymph node dissection. Postoperative pathological examination showed that 22 cases were Hurthle cell adenomas and 6 cases were Hurthle cell carcinomas, 1 of them with cervical lymph node metastasis. Twenty-one patients with Hurthle cell adenomas were followed up for 6 months to 7.5 years (with a median of 45 months) and 6 patients with Hurthle cell carcinomas for 3 to 8 years (with a median of 54 months), with no recurrence and death case. CONCLUSIONS: HCT is a potential malignant neoplasm. There are some difficulties in the diagnosis of HCT by frozen section. Surgery is an effective treatment for HCT. L-Thyroxine can be used to inhibit TSH excretion.