Regan Sheena L P, Knight Phil G, Yovich John L, Stanger James D, Leung Yee, Arfuso Frank, Dharmarajan Arun, Almahbobi Ghanim
Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights, Reading RG6 6UB, UK.
Mol Cell Endocrinol. 2017 May 5;446:40-51. doi: 10.1016/j.mce.2017.02.007. Epub 2017 Feb 7.
The low take-home baby rate in older women in Australia (5.8%) undergoing IVF (5.8%) is linked to the depletion of the ovarian reserve of primordial follicles. Oocyte depletion causes an irreversible change to ovarian function. We found that the young patient FSH receptor and LH receptor expression profile on the granulosa cells collected from different size follicles were similar to the expression profile reported in natural cycles in women and sheep. This was reversed in the older patients with poor ovarian reserve. The strong correlation of BMPR1B and FSH receptor density in the young was not present in the older women; whereas, the LH receptor and BMPR1B correlation was weak in the young but was strongly correlated in the older women. The reduced fertilisation and pregnancy rate was associated with a lower LH receptor density and a lack of essential down-regulation of the FSH and LH receptor. The mechanism regulating FSH and LH receptor expression appears to function independently, in vivo, from the dose of FSH gonadotrophin, rather than in response to it. Restoring an optimum receptor density may improve oocyte quality and the pregnancy rate in older women.
在澳大利亚,接受体外受精(IVF)的老年女性的低活产率(5.8%)与原始卵泡卵巢储备的耗竭有关。卵母细胞耗竭会导致卵巢功能发生不可逆的变化。我们发现,从不同大小卵泡收集的年轻患者颗粒细胞上的促卵泡激素(FSH)受体和促黄体生成素(LH)受体表达谱与女性和绵羊自然周期中报道的表达谱相似。在卵巢储备差的老年患者中则相反。年轻女性中骨形态发生蛋白受体1B(BMPR1B)与FSH受体密度的强相关性在老年女性中不存在;而LH受体与BMPR1B的相关性在年轻女性中较弱,但在老年女性中相关性很强。受精率和妊娠率降低与较低的LH受体密度以及FSH和LH受体缺乏必要的下调有关。调节FSH和LH受体表达的机制在体内似乎独立于FSH促性腺激素的剂量起作用,而不是对其作出反应。恢复最佳受体密度可能会改善老年女性的卵母细胞质量和妊娠率。