Merhi Zaher, Thornton Kimberley, Bonney Elizabeth, Cipolla Marilyn J, Charron Maureen J, Buyuk Erkan
Department of Obstetrics and Gynecology, Division of Reproductive Biology, New York University School of Medicine, 180 Varick Street, sixth floor, New York, NY, 10014, USA.
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA.
J Assist Reprod Genet. 2016 Apr;33(4):535-43. doi: 10.1007/s10815-016-0672-x. Epub 2016 Feb 15.
The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1).
Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR).
In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs.
These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.
本研究的目的是检验以下假设,即卵巢中的亲吻素(kiss1)及其受体(kiss1r)的表达受年龄、肥胖以及与年龄和肥胖相关的趋化因子单核细胞趋化蛋白-1(MCP-1)的影响。
收集喂食正常饲料(NC)或高脂(HF)饮食的生殖年龄和老年C57BL/6J小鼠的卵巢、年龄匹配的NC喂养的年轻MCP-1基因敲除小鼠和年轻对照小鼠的卵巢,最后收集接受体外受精(IVF)的女性的卵丘和壁层颗粒细胞(GCs)。使用实时聚合酶链反应(RT-PCR)对Kiss1、kiss1r、抗苗勒管激素(AMH)和AMH受体(AMHR-II)信使核糖核酸(mRNA)的表达水平进行定量。
在小鼠卵巢中,与生殖年龄小鼠相比,老年小鼠的kiss1和kiss1r mRNA水平显著更高,饮食诱导的肥胖并未改变kiss1或kiss1r mRNA水平。与年轻对照小鼠相比,年轻的MCP-1基因敲除小鼠的卵巢kiss1 mRNA水平显著降低,但AMH和AMHR-II mRNA水平显著升高。在人类卵丘颗粒细胞中,kiss1r mRNA水平与年龄呈正相关,但与体重指数无关。在卵丘或壁层颗粒细胞中均未检测到kiss1 mRNA的表达。
这些数据表明,亲吻素能系统在卵巢生理中可能具有与年龄相关的生理作用。此外,炎症因子MCP-1可能分别与在排卵和卵泡发生中起重要作用的kiss1和AMH基因相关。