白藜蘆醇保護高齡小鼠不孕

 

Human Reproduction  2013年1月4日。搶鮮版  

 

出處:第二名的不孕症期刊

 

 

白藜蘆醇保護高齡小鼠不孕

 

 

細胞生物學與遺傳學系，藥物化學生物學國家重點實驗室，生命科學學院，南開大學，天津 300071，中國。

抽象
研究的問題：
白藜蘆醇抵消年齡相關的不孕生殖衰老小鼠模式的嗎？
摘要答案：
長期口服白藜蘆醇對減少生育與生殖衰老小鼠的保護。
什麼是已知的了：卵巢老化和不育的卵母細胞和卵泡及卵母細胞質量下降的損失歸因於與年齡老化。隨著年齡的增長自由基的積累導致DNA突變，蛋白質損傷，端粒縮短，細胞凋亡，加速卵巢衰老。越來越多的證據表明，白藜蘆醇，豐富了某些食物，例如紅葡萄和葡萄酒，體細胞具有抗腫瘤和抗衰老的作用，通過影響不同的信號轉導通路，包括抗氧化，以及激活SIRT1和端粒酶。我們研究了潛在的白藜蘆醇，以延緩卵巢衰老的近交系的C57/BL6小鼠模型。
研究設計，大小，持續時間：
年輕C57/BL6女性（年齡在2-3個月）被餵食白藜蘆醇添加到飲用水在30毫克/升〜7.0毫克/公斤/天，6個月或12個月的生育和卵巢功能比較帶或不帶白藜蘆醇治療的老鼠，與年輕小鼠生殖控制。實驗重複3次，每個重複，女25例，隨機平均分配到每個治療組。
參加者/材料，設置方法：
雌性小鼠的繁殖性能是決定產仔數，卵巢內的卵泡及卵母細胞的數量和質量，並與年齡匹配的對照比較。白藜蘆醇對端粒和端粒酶的活性，並與細胞衰老相關基因的表達的影響也進行了評估。
主要結果和角色的機會：
年輕老鼠餵食白藜蘆醇12個月，保留了生育能力，而年齡匹配的對照組沒有子代，為12個月餵白藜蘆醇的小鼠表現出較大的卵泡池比對照組（P <0.05）。此外，端粒酶活性，端粒長度與年齡有關的基因在餵白藜蘆醇的小鼠卵巢中的表達相似，那些年輕的老鼠，但是從這些年齡相匹配的老年小鼠差異（P <0.05）。白藜蘆醇改善（P <0.05）卵母細胞的數量和質量，就證明了紡錘體形態和染色體定位。此外，白藜蘆醇在體外以劑量依賴性的方式受影響的胚胎發育。
限制，謹慎的理由：
的劑量白藜蘆醇的實驗條件下使用不同的研究小組有各種不同的影響很大，而且劑量的白藜蘆醇的有效性和毒性。微調劑量的白藜蘆醇可能對卵巢功能優化其抗衰老的作用。
更廣泛的影響的研究結果：
我們的數據提供了一個證明的原則，在雌性小鼠的白藜蘆醇的保留生育功能的影響。雖然消耗的卵巢儲備功能的高品質的卵母細胞，也有助於增加女性不孕不育與生殖衰老，獲得的數據使用的小鼠模型可能無法直接推斷到人類的繁衍，如果任何臨床試驗嘗試。以及更廣泛的研究是必要的。

 

陳醫師的意見

 

儘管這是用年紀大的小鼠的動物實驗,研究證實高齡老鼠卵巢功能不足，而長期服用白藜蘆醇改善（P <0.05）卵母細胞的數量和質量，就證明了紡錘體形態和染色體穩定。人類尚無此研究。

 

Hum Reprod. 2013 Jan 4. [Epub ahead of print]

Resveratrol protects against age-associated infertility in mice.

Liu M, Yin Y, Ye X, Zeng M, Zhao Q, Keefe DL, Liu L.

Source

Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences; Nankai University, Tianjin 300071, China.

Abstract

STUDY QUESTION:

Does resveratrol counteract age-associated infertility in a mouse model of reproductive aging?

SUMMARY ANSWER:

Long-term-oral administration of resveratrol protects against the reduction of fertility with reproductive aging in mice.

WHAT IS KNOWN ALREADY:

Loss of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian aging and infertility. Accumulation of free radicals with age leads to DNA mutations, protein damage, telomere shortening, apoptosis and accelerated ovarian aging. Increasing evidence shows that resveratrol, enriched in certain foods, for example red grapes and wine, has anti-tumor and anti-aging effects on somatic tissues by influencing various signaling pathways, including anti-oxidation, as well as activating Sirt1 and telomerase. We investigated the potential of resveratrol to stave off ovarian aging in the inbred C57/BL6 mouse model.

STUDY DESIGN, SIZE, DURATION:

Young C57/BL6 females (aged 2-3 months) were fed with resveratrol added to drinking water at 30 mg/l (providing ∼7.0 mg/kg/day) for 6 or 12 months, and the fertility and ovarian functions were compared among mice treated with or without resveratrol, and young mice served as reproductive controls. Experiments were repeated three times, with an average of 25 females randomly allocated to each treatment group for each repeat.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Reproductive performance of female mice was determined by litter size, ovarian follicles and oocyte quantity and quality, and compared with age-matched controls. The impact of resveratrol on telomeres and telomerase activity, and expression of genes associated with cell senescence also was evaluated.

MAIN RESULTS AND THE ROLE OF CHANCE:

Young mice fed with resveratrol for 12 months retained the capacity to reproduce, while age-matched controls produced no pups. Consistently, mice fed with resveratrol for 12 months exhibited a larger follicle pool than controls (P < 0.05). Furthermore, telomerase activity, telomere length and age-related gene expression in ovaries of mice fed with resveratrol resembled those of young mice, but differed (P < 0.05) from those of age-matched old mice. Resveratrol improved (P < 0.05) the number and quality of oocytes, as evidenced by spindle morphology and chromosome alignment. Also, resveratrol affected embryo development in vitro in a dose-dependent manner.

LIMITATIONS, REASONS FOR CAUTION:

The doses of resveratrol and the experimental conditions used by different research groups have varied considerably, and the dosage influences both the effectiveness and toxicity of resveratrol. Fine-tuning the dosage of resveratrol likely will optimize its anti-aging effects on ovarian function.

WIDER IMPLICATIONS OF THE FINDINGS:

Our data provide a proof of principle of the fertility-sparing effect of resveratrol in female mice. Although depletion of the ovarian reserve of high-quality oocytes also contributes to increased infertility with reproductive aging in women, the data obtained using a mouse model may not extrapolate directly to human reproduction, and more extensive research is needed if any clinic trials are to be attempted.