粒線體的激活可能提供了新方法提高試管嬰兒的婦女高齡的成果

 

粒線體(有如細胞的電池)

[O – 116]年齡在胚胎發育的相關下降可以逆轉的粒線體代謝活化的小鼠模式

澳大利亞阿德萊德大學,阿德萊德


目的:年齡在胚胎激活線粒體的新陳代謝下,提高胚胎發育和生存能力,因此妊娠成功。
設計:越來越多的婦女延遲生育,但是女人年齡的增加而生育率下降。在過去 10年中已經出現了懷孕率顯著改善試管嬰兒,但是這一增長幾乎完全是年輕婦女改善的結果。從中年婦女的卵母細胞線粒體活性降低,導致在胚胎發育和活力減少。因此,我們假設歲的胚胎治療與線粒體代謝的刺激會顯著改善線粒體的健康,因此,提高胚胎發育。
材料和方法:瑞士小鼠年齡在24週的高齡雌性鼠超排卵,並與瑞士男性小鼠的交配。受精卵收集和分配來控制(G1/G2)或DCAG1/G2輔以DCA130μg/ml)培養 96小時,在5O2胚囊的發展進行了評估 4日及5和總細胞數,ICM和外胚層發展的決心。線粒體代謝是由2 – 14C丙酮酸氧化和JC1熒光。由一般線性模型和LSD的數據進行分析。
結果:受精卵與添加DCA增加了4天,5天(P <0.05)囊胚的發展。進一步 DCA的顯著增加(P <0.05),總細胞數(133.5 ± 11.4163.1 ± 11.8),內細胞團(23.5 ± 2.628.2 ± 2.8)和外胚層(6.2 ± 0.9 VS 8.2 ± 1.0)。DCA的培養歲的胚胎在2細胞(0.21 ± 0.040.41 ± 0.05pmol/e/hr)丙酮酸氧化顯著增加,囊胚(0.13 ± 0.020.23 ± 0.03pmol/e/hr)(P < 0.01),線粒體膜電位(P <0.05)。
結論:我們已經表明,年齡受精卵培養與線粒體的刺激劑提高胚胎的代謝,增加了關鍵的發展措施,這表明,線粒體的激活可能提供了新方法提高試管嬰兒的婦女>40歲的成果。

 

陳啟煌醫師的意見:

這是我於201110月中旬參加美國生殖學會年會

(67th ASRM Annual Meeting, ORLANDO 2011)

比較欣賞的研究發表之一,以高齡的瑞士鼠添加粒線體的刺激劑改善胚胎品質,儘管沒有人體試驗,而從事動物實驗總在用於人之前。高齡細胞老化,粒線體老化,若能激活高齡的生物的胚胎和很多人服用健康食品希望卵及胚胎品質提升不謀而合,當然此篇並沒有展現懷孕率及活產率也是可惜。

原文

[O-116] AGE RELATED DECLINE IN EMBRYO DEVELOPMENT CAN BE REVERSED BY ACTIVATION OF MITOCHONDRIAL METABOLISM IN A MOUSE MODEL.

 

M. Lane, N. O. Palmer Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA, Australia; Repromed, Dulwich, SA, Australia

 

OBJECTIVE: To activate mitochondrial metabolism in aged embryos to improve embryo growth and viability and therefore pregnancy success.

DESIGN: Increasingly women are delaying childbearing however fertility declines as a woman ages. In the last 10 years there have been a significant improvement in pregnancy rates following IVF however this increase is almost exclusively the result of improvements for young women. Oocytes from aged women have reduced mitochondrial activity resulting in a reduction in embryo development and viability. Therefore, we hypothesised that treatment of aged embryos with a stimulator of mitochondrial metabolism would significantly improve mitochondrial health and therefore improve embryo development.

MATERIALS AND METHODS: Swiss female mice aged 24 weeks were superovulated and mated with a Swiss male. Zygotes were collected and allocated to either, control (G1/G2) or DCA (G1/G2 supplemented with 130µg/ml of dichloroacetate) and cultured for 96h in 5%O2. Blastocyst development was assessed on day 4 and 5 and total cell number, ICM and epiblast development determined. Mitochondrial metabolism was determined by 2-14C-pyruvate oxidation and JC1 fluorescence. Data was analysed by a general linear model and LSD.

RESULTS: Culture of aged zygotes with DCA increased blastocyst development on day 4 and day 5 (p<0.05). Further DCA significantly increased (p<0.05) total cell number (133.5±11.4 vs 163.1±11.8), inner cell mass (23.5±2.6 vs 28.2±2.8) and epiblast (6.2±0.9 vs 8.2±1.0). Aged embryos cultured in DCA had a significant increase in pyruvate oxidation at both the 2 cell (0.21±0.04 vs 0.41±0.05pmol/e/hr) and blastocyst (0.13±0.02 vs 0.23±0.03pmol/e/hr) (p<0.01) and mitochondrial membrane potential (P<0.05).

CONCLUSION: We have shown that aged zygotes cultured with a mitochondrial stimulant improves embryo metabolism and increased key developmental measures, suggesting that activation of the mitochondria may provide a novel method for improving IVF outcomes in women >40years.

Supported by: NHMRC

 

 

Tuesday, October 18, 2011 12:45 PM



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