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 mare's 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.
Joo
Jong-Kil
JK
Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University School of Medicine, 1-10 Amidong, Seuku, Busan, Republic of Korea.
Joo
Bo-Sun
BS
Kim
Seung-Chul
SC
Choi
Jong-Ryeol
JR
Park
Sae-Hee
SH
Lee
Kyu-Sup
KS
D000375:Aging; D000818:Animals; D001755:Blastocyst / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000008:administration & dosage; D046149:Embryo Culture Techniques / Q000662:veterinary; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006064:Gonadotropins, Equine / Q000008:administration & dosage; D020738:Leptin / Q000008:administration & dosage* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes / Q000502:physiology*; D010053:Ovary / Q000098:blood supply* / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage; D013480:Superovulation; D020858:Tissue and Organ Harvesting / Q000662:veterinary; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D020738:Leptin; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A