(3)卵の老化機構の解明 : 卵の加齢による細胞内カルシウム制御機構の変化(<特集>第60回学術講演会要旨シンポジウム2「卵の発育・成熟・老化機構の解明と臨床応用」)
スポンサーリンク
概要
- 論文の詳細を見る
The fertilizable lifespan of mammalian oocytes is remarkably short, less than 10hr. Post ovulatory-aging of oocytes, not being fertilized for a prolonged time after ovulation in the ampulla of the oviduct, is known to significantly impair the embryo development. In mammalian oocytes, fusion of the sperm to the oolemma at fertilization induces a large transient increase in the cytosolic Ca^<2+> concentration followed by repetitive short transient elevation of Ca^<2+> lasting for several hours. These temporal changes in Ca^<2+> are called Ca^<2+> oscillations. The increase in intracellular Ca^<2+> plays an important role at fertilization, such as cortical granule exocytosis, resumption of meiosis, pronucleus formation and embryos development. We hypothesize the poor embryo development of post-ovulatory aged oocytes is related to the changes in Ca^<2+> oscillations at fertilization. In this study, we examined the relationship between post-ovulatory aging and Ca^<2+> handling in the mouse oocytes. The oocytes recovered from the oviduct after 14hr hCG injection were referred to as fresh oocytes while the oocytes recovered from the oviduct after 20hr hCG injection were referred to as aged oocytes. We showed that the post-ovulatory aging significantly altered the patterns of Ca^<2+> oscillations at fertilization. Frequency of Ca^<2+> oscillations in aged oocytes was significantly higher than in fresh oocytes while the amplitude of individual Ca^<2+> oscillations was significantly lower in the aged oocytes. We further showed that both Ca^<2+> reuptake by Ca^<2+> -ATPase in the endoplasmic reticulum (ER) and inositol 1, 4, 5-triphosphate (IP_3)-induced Ca^<2+> release from the ER were significantly decreased in the aged oocytes. Moreover, we showed that intracellular Ca^<2+> store of the ER was significantly decreased in the aged oocytes. Experimentally decreasing of Ca^<2+> store in the fresh oocytes by specific ER Ca^<2+> -ATPase inhibitor thapsigargin resulted in the detrimental embryo development and the abnormal Ca^<2+> oscillations at fertilization, such as lower amplitude and higher frequency. We surmised that the poor embryo development of the aged oocytes may arise from inadequate Ca^<2+> handling due to mitochondrial dysfunction. Thus, we examined the ATP production and mitochondrial membrane potential in the fresh and aged oocytes, and found that both ATP production and membrane potential in the aged oocytes were significantly decreased. Finally, we examined the effects of oxidative stress on the embryo development and the Ca^<2+> oscillations at fertilization. We revealed that the poor embryo development and the abnormal Ca^<2+> oscillations, which were similar to aged oocytes, were observed in hydrogen peroxide-treated fresh oocytes. Taken together, these findings support the idea that Ca^<2+> oscillations play a key role in the development of fertilized aged oocytes.
- 社団法人 日本産科婦人科学会の論文
- 2008-10-01
著者
関連論文
- P1-12 GFP結合ERαを用いた子宮内膜細胞におけるエストロゲン,抗エストロゲン作用の可視化(Group2 生殖生理・病理1,一般演題,第62回日本産科婦人科学会学術講演会)
- P3-144 婦人科悪性腫瘍患者における術後静脈血栓塞栓症予防に関する臨床的検討 : 高リスク群に対する間欠的空気圧迫法の限界(Group116 婦人科腫瘍血栓症2,一般演題,第62回日本産科婦人科学会学術講演会)
- 診療 クエン酸クロミフェンによる子宮内膜増殖抑制作用の分子機構
- P1-212 化学療法後の卵巣癌再発巣におけるAktとERKの活性化は予後良好因子である(Group26 卵巣腫瘍2,一般演題,第62回日本産科婦人科学会学術講演会)
- 25-18.受精時の細胞内ATP測定による卵の質の評価 : マウス加齢卵を用いた検討(第121群 生殖生理・病理10)(一般演題)
- 術前診断後、腹腔鏡下に摘出し得た副角妊娠(9週)の1症例
- P3-337 エストロゲンの血管内皮機能改善作用に対するジェノゲストの影響に関する基礎的・臨床的検討(Group118 女性医学基礎,一般演題,第61回日本産科婦人科学会学術講演会)
- P3-301 脂質異常を有するクロミフェン抵抗性多嚢胞性卵巣症候群に対するベザフィブレートの排卵促進効果の検討(Group113 生殖内分泌1,一般演題,第61回日本産科婦人科学会学術講演会)
- 卵成熟とプロスタグランジン : ノックアウトマウスから学ぶ
- マウス卵巣組織におけるガングリオシドGD2の局在