Bo-Sun Joo

Role of leptin in improvement of oocyte quality by regulation of ovarian angiogenesis.

Ovarian angiogenesis plays an important role in folliculogenesis. An active blood supply via ovarian angiogenesis seems to be essential for the induction of oocytes with good quality. Leptin is an angiogenic factor which regulates VEGF expression. This study was aimed to investigate whether leptin administration during superovulation influences ovarian response, oocyte quality and VEGF expression in the ovary using different aged mice model. C57BL inbred female mice of two age groups (18-21, and 29-31 weeks) were superovulated by intraperitoneal co-injection with 5IU of pregnant mares serum gonadotropin (PMSG) supplemented with recombinant mouse leptin at various doses (0.01, 0.1, 1 microg), followed by injection with 5IU of human chorionic gonadotropin (hCG) approximately 48 h later. Then, the mice were immediately paired with an individual male. The control group was superovulated with PMSG and hCG without leptin. After 18 h, one-cell embryos were flushed and cultured for 4 days. Proteins were extracted from ovaries removed just after the retrieval of one-cell embryos and VEGF expression was examined by Western blot. Treatment of 0.1 microg and 1 microg leptin significantly increased the number and embryo development rate of one-cell embryos retrieved compared to the control group. This positive effect of leptin was more significant with advancing female age. Ovarian VEGF expression was also significantly increased in 0.1 and 1 microg leptin-treated groups compared to the control group in both age groups (P<0.05). Our present study showed that leptin administration with gonadotropins during superovulation in aged mice increased the ovarian response, developmental competence of oocytes and ovarian VEGF expression. This research may have potential clinical implications in the treatment of age-related decline of fertility.

Decreased expressions of vascular endothelial growth factor and visfatin in the placental bed of pregnancies complicated by preeclampsia

Aim:  The aim of the present study was to examine the expression of vascular endothelial growth factor (VEGF) and visfatin in the third trimester placental bed of pregnancies with and without preeclampsia (PE).

Administration of visfatin during superovulation improves developmental competency of oocytes and fertility potential in aged female mice

OBJECTIVE To examine whether visfatin administration during superovulation improves ovarian response, developmental competence of oocytes, and fertility in aged female mice. DESIGN Controlled experimental study. SETTING University hospital. ANIMAL(S) Two groups of differently aged C57BL female mice (6-11 and 26-31 weeks). INTERVENTION(S) Female mice were coinjected intraperitoneally with 5 IU pregnant mares serum gonadotropin (PMSG) and visfatin of various doses (0-500 ng/mL), followed by 5 IU human chorionic gonadotropin (hCG) injection 48 hours later. Then the mice were immediately mated with an individual male. After 18 hours zygotes were cultured, and expression of ovarian visfatin and vascular endothelial growth factor (VEGF) was examined. Potential pregnancies of visfatin-administered aged female mice were monitored for delivery of offspring. MAIN OUTCOME MEASURE(S) Number of zygotes retrieved, embryo developmental competency, fertility potential, ovarian visfatin and VEGF expression. RESULT(S) Ovarian visfatin expression was significantly decreased in the aged mice group compared with the young. Visfatin administration significantly increased embryo developmental rate and ovarian visfatin and VEGF expressions in the aged mice. Visfatin-administered aged mice delivered significantly higher numbers of offspring than controls. CONCLUSION(S) This study suggests that visfatin administration during superovulation plays an important role in regulating oocyte quality and can improve oocyte quality and fertility of aged female mice.

Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovary

Aims:  This study investigated whether estrogen administration during superovulation enhances oocyte quality using a mice model. We also investigated whether this estrogen treatment regulates the expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), in the ovary.

Sodium nitroprusside treatment during the superovulation process improves ovarian response and ovarian expression of vascular endothelial growth factor in aged female mice

OBJECTIVE To investigate whether sodium nitroprusside (SNP) treatment during the superovulation process improves ovarian response and oocyte developmental competence in aged female mice. DESIGN Controlled experimental study. SETTING Large urban medical center. ANIMAL(S) C57BL inbred female mice of three age groups: 6 to 9, 14 to 16, and 25 to 27 weeks. INTERVENTION(S) Female mice were co-injected intraperitoneally with SNP (1 muM or 10 muM) and pregnant mares serum gonadotropin (PMSG), followed by human chorionic gonadotropin injection 48 hours later and then mated with individual males. After 18 hours, zygotes were flushed and the ovaries were isolated. The control group was injected with PMSG. MAIN OUTCOME MEASURE(S) The number of zygotes flushed, embryo development to blastocyst stage, and vascular endothelial growth factor (VEGF) expression in ovary. RESULT(S) Treatment with SNP statistically significantly increased the number of flushed zygotes and blastocyst formation rate in mice aged 25 to 27 weeks, not but in mice aged less than 16 weeks compared with the control group. The SNP treatment in aged mice increased VEGF expression of the ovary in a dose-dependent manner. CONCLUSION(S) These results demonstrate that SNP treatment during the superovulation process improves ovarian response and oocyte developmental competence in aged female. The positive effect of SNP may be associated with increased VEGF expression.

Differential expressions of stromal cell-derived factor-1α and vascular endothelial growth factor in the placental bed of pregnancies complicated by preeclampsia.

Objective: The aim of this study is to examine the differential expression of stromal cell-derived factor-1α (SDF-1α)/CXCR4 and vascular endothelial growth factor (VEGF) in the third trimester placental bed of normotensive controls and preeclamptic patients. Methods: Placental bed tissues were collected from 15 patients with preeclampsia (PE) and 15 gestational-matched normotensive controls at the time of their cesarean delivery. Placental bed expressions of SDF-1α, CXCR4 and VEGF were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemical staining. Results: No statistical difference was found between the PE and the normotensive control group with respect to their age and parity, gravidity and body mass index. The placental bed expressions of SDF-1α/CXCR4 and VEGF were significantly decreased in the PE group compared with the normotensive control group. Conclusions: This study showed decreased expressions of SDF-1α/CXCR4 and VEGF in the third trimester placental bed of pregnancies with PE. This result suggests that decreased expressions of SDF-1α/CXCR4 and VEGF in the placental bed could be associated with the pathogenesis of PE.

Prediction of multiple pregnancies by the number of early cleaving embryos

Aim:  The aim of the present study was to investigate the number of early cleaving embryos as an effective predictor for multiple pregnancies in human in vitro fertilization (IVF).

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. TGF-β1 and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of TGF-β1 on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endome-triotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to meso-thelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane. Taken together, these results suggest that TGF-β1 may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

Effects of three-area laser-assisted zona thinning in 8-cell human embryos on pregnancy outcomes in vitro fertilization

Objective This study conducted a preliminary examination of the effects of three-area laser-assisted zona thinning (LAZT) during the cleavage stage of embryo development on the hatching process in human in vitro fertilization-embryo transfer (IVF-ET) with subjects of advanced female age or frozen-thawed (FT) embryos. Methods Eight-cell stage embryos were treated with LAZT in three areas of the zona pellucida at 120° intervals. The control group was embryos without LAZT. Of the 72 consecutive fresh cycles and the 28 FT embryo transfer cycles, the patients in 55 fresh cycles and 17 FT cycles declined LAZT, and those cycles were defined as the control group. Results In the fresh cycles, the pregnancy rates were similar in the LAZT and control groups. However, in the FT cycles, the pregnancy rate was significantly higher in the LAZT group than in the control group (45.5% in the LAZT group vs. 23.5% in the control group, p<0.05). Conclusion These results show that multi-area LAZT resulted in significantly improved pregnancy outcomes in human 8-cell embryos compared to controls.