Fertility Outcome and Safety of Ethiodized Poppy Seed Oil for Hysterosalpingography in 1,053 Infertile Patients: A Real-World Study.

Objective: Ethiodized poppy seed oil for hysterosalpingography (HSG) is reported to display some therapeutic effect on infertility, but big a sample-size study under real clinical settings is still lacking to verify the speculation. Thus, this real-world study enrolled 1,053 infertile patients who underwent ethiodized poppy seed oil-based HSG to explore its fertility enhancement value. Method: A total of 1,053 infertile patients who underwent HSG using ethiodized poppy seed oil as the contrast medium were retrospectively analyzed. The live birth rate and 3-, 6-, 12-month and total pregnancy rate were retrieved. Besides, adverse events during and after HSG were recorded. Results: The 3-, 6-, 12-month and total pregnancy rate was 22, 36.8, 50, and 53.8%, respectively. The total live birth rate was 42.7%. Sub-group analyses showed that pregnancy rate was 53.7, 53.8, 54.1, and 62.4% in subgroups of primary infertility patients, secondary infertility patients, infertility patients with fallopian tube disease, and infertility patients with unknown cause, respectively. Meanwhile the live birth rate was 44.3, 41.3, 41.5, and 59.2% in these subgroups, separately. Multivariate logistic regression analysis disclosed that BMI ≥ 24 kg/m2, history of dysmenorrhea, and abnormity of sperm count or motility-related infertility were independently correlated with reduced pregnancy rate and livebirth rate (All Ps < 0.05). Adverse events mainly included pain (20.6%) and interstitial reflux (7.9%), which were mild and tolerable. Conclusion: Ethiodized poppy seed oil for HSG discloses a satisfying fertility outcome with a tolerable safety profile in infertile patients; meanwhile, this effect might be influenced by BMI, history of dysmenorrhea, and paternal abnormity of sperm.

FoxO3a negatively regulates nerve growth factor-induced neuronal differentiation through inhibiting the expression of neurochondrin in PC12 cells.

Forkhead box O3 (FoxO3a) is a forkhead family transcription factor playing important roles in non-neuronal differentiation, metabolism, proliferation, and survival, but its role in neuronal differentiation remains unclear. In the present study, we investigated the role of FoxO3a in neuronal differentiation and its underlying mechanisms. Our results showed that overexpression of FoxO3a inhibited neuronal differentiation of PC12 cells induced by nerve growth factor (NGF) while knockdown of FoxO3a by siRNA enhanced NGF-induced differentiation. DNA microarray analysis and quantitative reverse transcription PCR (RT-PCR) showed that the overexpression of FoxO3a significantly attenuated expression of neurochondrin (NCDN), a neurite outgrowth-related protein, in PC12 cells, while knocking down the expression of FoxO3a had the opposite effect. Bioinformatic studies found that the regulatory region of NCDN promoter contained multiple FoxO3a binding sites. Dual-luciferase reporter assay with report gene containing NCDN promoter showed that FoxO3a significantly decreased the transcription activity of NCDN promoter. These results indicate that NCDN is a direct downstream target of FoxO3a which negatively regulates the expression of NCDN. Interestingly, NGF-induced NCDN expression and cell differentiation was blocked by the inhibition of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (PKB, Akt) signal pathway (activation of FoxO3a) and overexpression of FoxO3a. Moreover, knockdown of NCDN by siRNA blocked NGF-induced neuronal differentiation of PC12 cells while overexpression of NCDN significantly promoted neurite outgrowth. These results put together demonstrate that NCDN plays an important role in NGF-induced neuronal differentiation and suggest that FoxO3a inhibits NGF-induced neuronal differentiation, at least in part, by suppressing the expression of NCDN.

Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells.

Insulin-like growth factor-1 (IGF-1) is a polypeptide tropic factor that plays an important role in the survival and differentiation of both neuronal and non-neuronal cells. Numerous studies have demonstrated that IGF-1 promotes neuronal cell survival via the PI3K/Akt signaling pathway. Proline-rich Akt substrate of 40kDa (PRAS40) is a recently discovered downstream target of Akt. However, the relationship between IGF-1 and PRAS40 is not known. In this study, we characterized the phosphorylation of PRAS40 induced by IGF-1 in PC12 cells and explored the signaling pathway responsible for the effect of IGF-1. IGF-1 induced the phosphorylation of Akt at Thr473 and PRAS40 at Thr246 in PC12 cells. The phosphorylation of Akt and PRAS40 induced by IGF-1 (100ng/ml) was inhibited by the phosphatidylinositide 3-kinase (PI3K) specific inhibitor LY294002 (50µM), while no inhibitory effect was observed for a MAPK kinase pathway specific inhibitor PD98059 nor a p38 MAPK inhibitor PD169316, suggesting that the phosphorylation of PRAS40 induced by IGF-1 is mediated by the PI3K pathway in PC12 cells and primary cultured neurons. In further support this hypothesis, an Akt kinase specific inhibitor, Akt inhibitor VIII, attenuated IGF-1-induced phosphorylation of PRAS40 at the concentration that blocked the phosphorylation of Akt induced by IGF-1. Taken together, these data demonstrate that IGF-1 stimulates the phosphorylation of PRAS40 at Thr246 in neuronal cells and the effect of IGF-1 is mediated, at least in part, by the PI3K/Akt signaling pathway.