GALNT14 regulates ferroptosis and apoptosis of ovarian cancer through the EGFR/mTOR pathway.

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from seven patients with PCOS and seven matched women. GC samples were collected during 2014 to 2016 from infertile women in Guangzhou, China. Quantitative real-time polymerase chain reaction was used to measure levels of the lncRNA HCG26 in GCs from 53 patients with PCOS and 50 controls. HCG26 was knocked down with locked nucleic acid GapmeRs in KGN cells to examine its role in cell proliferation, aromatase and follicle-stimulating hormone receptor gene expression, and estradiol production. A total of 862 lncRNA transcripts and 998 messenger RNA transcripts were differentially expressed (greater than or equal to twofold change; P < 0.05) in PCOS GCs compared with those of controls. HCG26 levels were upregulated in patients with PCOS and were associated with antral follicle count. HCG26 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression and increased aromatase gene expression and estradiol production. Our study reports the lncRNA profiles in GCs from patients who have PCOS and those from healthy women and suggests that dysregulated lncRNAs may play vital roles in GC proliferation and steroidogenesis, providing insights into the pathogenesis of PCOS.

[Pregnancy outcome in a woman with premature ovarian insufficiency complicated by systemic lupus erythematosus during pregnancy: a case report].

OBJECTIVE: We report a case of in vitro fertilization and embryo transfer (IVF?ET) with oocyte donation in a woman with premature ovarian insufficiency (POI) complicated by systemic lupus erythematosus (SLE) during pregnancy. The patient had a diagnosis of POI 4 years earlier and 11 weeks after successful pregnancy by IVF?ET with oocyte donation in 2003, she presented with facial edema, and further examinations confirmed the diagnosis of lupus nephritis. She received treatment with prednisone to control the activity of SLE and aspirin and low?molecular?weight heparin to improve placental blood flow with close monitoring of gravida and fetus throughout pregnancy. The condition of the patient remained unstable during pregnancy, and liver damage and placental circulation disorder occurred in late gestational weeks with suspected intrauterine growth retardation (IUGR) of the fetus. For maternal and fetal safety, the patient received elective caesarean section and delivered a premature boy at 31 weeks of gestation. She subsequently received further medications for SLE and showed good recovery of the immunological parameters and absence of SLE symptoms during the follow?up for 14 years, indicating a clinical cure of SLE. Her son shows normal growth and development. Based on the experience with this case and literature review, we believe that immunological factor is an important cause of POI and thus recommend full immunological examinations in cases of idiopathic POI.

[Clinical outcome of in vitro fertilization or intracytoplasmic sperm injection-embryo transfer in women aged 40 years and above].

OBJECTIVE: To investigate the clinical outcomes in vitro fertilization or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women aged over 40 years. METHODS: We retrospectively analyzed 1050 non-donor IVF/ICSI-ET cycles performed from January, 2007 to December, 2015 in women at the age 40 years or above, including 393 women at 40 years of age, 266 at 41 years, 158 at 42 years, 107 at 43 years, 64 at 44 years, and 65 at 45-51 years. The clinical characteristics and outcomes of the women in different age groups were compared and analyzed. The pregnancy outcome of different ovarian stimulation protocols and different numbers of embryo transferred were also compared. RESULTS: Oocyte retrieval was achieved in 1032 treatment cycles. Of the 750 embryo transfer cycles, the clinical pregnancy rate was 17.7% (113/750), and the live birth rate was 8.5% (64/750). The clinical pregnancy rate in the 5 age groups was 23.4%, 21.0%, 13.1%, 9.2%, 5.6% and 0%, and the implantation rate was 11.2%, 10.2%, 6.3%, 5.1%, 2.3% and 0%, respectively; the early spontaneous abortion rate was 31.0%, 35.9%, 42.9%, 42.9% and 100%, and the live birth rate was 11.9%, 11.8%, 2.8% and 3.9%. The clinical pregnancy rates of long protocol, short prorocol, GnRHa antagonist protocol, and ovulation induction protocol were 23.6%, 10.2%, 13.3%, and 2.3%, respectively. In the 750 transfer cycles, the clinical pregnancy rate was 3.8% with single embryo transfer, 12.6% with double embryos transfer, and 23.0% with 3 embryos transfer. CONCLUSION: In women aged 40 years or above, the clinical pregnancy rate decreased significantly with age, and the live birth rate was extremely low in women aged beyond 44 years. Assisted reproductive technique is recommended for women aged 40 years and above even when no identifiable causes of sterility are present. For women aged above 44 years of age, oocyte donation may be a better option.

[Outcome analysis of monozygotic twin pregnancy conceived by assisted reproductive techniques].

OBJECTIVE: To analyze the incidence, management, and outcomes of monozygotic twin (MZT) pregnancy conceived by assisted reproductive techniques (ART). METHODS: A retrospective analysis was performed of clinical pregnancies after in vitro fertilization and embryo transfer (IVF-ET) and introcytoplasmic sperm injection and embryo transfer (ICSI-ET) from January, 2010 to June 2015 at our center. We investigated the incidence, managements and outcomes of 94 MZT pregnancies. Comparison of the pregnancy outcomes was made between the expectantly managed MZT pregnancies, dizygotic twin (DZT) pregnancies, monozygotic (MZ)-triplet pregnancies with selective embryo reduction (SER) to 2 fetuses and 1 fetus, and non-MZ triplet pregnancies with SER to 2 fetuses. RESULTS: Ninety-four MZT pregnancies occurred in the total of 6257 clinical pregnancy cycles with an incidence of 1.5%. No significant difference was found in the incidence of MZT pregnancies between IVF and ICSI cycles or between fresh and thawed cycles (P>0.05). Of the 94 MZT pregnancies, 45 were MZT pregnancy cycles, 43 were MZ-triplet pregnancy cycles, 3 were MZ-quadruplet pregnancy cycles and 3 were ectopic pregnancies. The expectantly managed MZT was associated with a significantly greater rate of miscarriage and malformation and a lower rate of live birth and term birth (P<0.05) in comparison with DZT pregnancy cycles that did not undergo SER. Similar outcomes were found between MZ-triplet pregnancies with SER to 2 fetuses and MZ-triplet pregnancies with SER to 1 fetus (P>0.05), and between MZ-triplets with SER to 2 fetuses and non-MZ triplet pregnancies with SER to 2 fetuses (P>0.05). CONCLUSION: ART is associated with a much higher incidence of MZT pregnancies than spontaneous conception. MZT pregnancies are at high risk of adverse outcomes, and reduction of MZT in multiple pregnancies may help to improve the outcomes.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Expression and clinical significance of vascular endothelial growth factor, cyclooxygenase-2, and Bcl-2 in borderline ovarian tumors.

OBJECTIVE: The objectives were to study the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), and Bcl-2 in borderline ovarian tumors (BOTs) and the relationship within them, and to investigate the correlation between expression of VEGF, Cox-2, and Bcl-2, and the clinicopathologic features of BOTs. METHODS: An immunohistochemical technique was used to investigate the expression of VEGF ,Cox-2, and Bcl-2 in 69 borderline, 18 benign, and 27 malignant human ovarian tumor tissues. RESULTS: Expression rate of VEGF protein (59.4%) in BOTs was higher than in benign tumors (27.8%) and was lower than in ovarian carcinomas (92.6%), and there was a significant difference between BOTs and benign ovarian tumors (p < 0.05), and carcinoma (p < 0.01). Significant correlation was observed between the positive expression rate for VEGF and clinical stage of BOTs (p < 0.05). The statistical analysis did not show a close correlation between the expression of VEGF and tissue type, and peritoneal implants in BOTs (p > 0.05). The expression rate of Cox-2 was significantly higher in ovarian carcinomas (81.5%) than in BOTs (57.9%) and in benign ovarian tumors (38.9%) (p < 0.05). Significant correlation was observed between the positive expression rate for Cox-2 and the clinical stage of BOTs (p < 0.05). The statistical analysis showed no close correlation between the expression of Cox-2 and tissue type, and peritoneal implants in BOTs (p > 0.05). There was a significant difference between the expression of Bcl-2 in ovarian carcinomas and BOTs than that in benign ovarian tumors (p < 0.05). The positive expression rate of Bcl-2 was not related to clinical stages and peritoneal implants (p > 0.05). Statistical analysis showed a positive correlation between the expression of Cox-2 and VEGF, and Bcl-2 in BOTs. CONCLUSIONS: Overexpression of VEGF, Cox-2, and Bcl-2 in BOTs may play an important role in the oncogenesis and progression of BOTs. It is feasible to detect VEGF, Cox-2, and Bcl-2 in the diagnosis and to predict the prognosis of BOTs.