FMR1 依赖的卵巢衰老模式变异性在年轻卵母细胞供体中已很明显。
FMR1-dependent variability of ovarian aging patterns is already apparent in young oocyte donors.
作者信息
Gleicher Norbert, Kim Ann, Barad David H, Shohat-Tal Aya, Lazzaroni Emanuela, Michaeli Tamar, Lee Ho-Joon, Kushnir Vitaly A, Weghofer Andrea
出版信息
Reprod Biol Endocrinol. 2013 Aug 16;11:80. doi: 10.1186/1477-7827-11-80.
BACKGROUND
Hypothesizing that redundant functional ovarian reserve (FOR) at young ages may clinically obfuscate prematurely diminished FOR (PDFOR), we investigated in young oocyte donors genotypes and sub-genotypes of the FMR1 gene, in prior studies associated with specific ovarian aging patterns, and determined whether they already at such young age were associated with variations in ovarian reserve (OR). We also investigated racial as well as FMR1 associations with menarcheal age in these donors.
METHODS
In a cohort study we investigated 157 oocyte donor candidates and, based on the 95% CI of AMH, divided them into normal age-specific (AMH greater or equal to 2.1 ng/mL; n = 121) and PDFOR (AMH < 2.1 ng/mL; n = 36). We then assessed associations between numbers of trinucleotide repeat (CGGn) on the FMR1 gene and FOR (based on anti-Müllerian hormone, AMH).
RESULTS
FMR1 did not associate with AMH overall. Amongst 36 donors with PDFOR, 17 (42%) presented with at least one low (CGGn < 26 ) allele. Remaining donors with normal FOR presented with significantly more CGGn greater or equal to 26 (73.6% vs. 26.4%; P = 0.024) and higher AMH (P = 0.012). This finding was mostly the consequence of interaction between FMR1 (CGGn < 26 vs. CGGn greater or equal to 26) and race (P = 0.013), with Asians most responsible (P = 0.009). Menarcheal age was in donors with normal FOR neither associated with race nor with FMR1 status. In donors with PDFOR race was statistically associated with CGGn (P = 0.018), an association primarily based on significantly delayed age of menarche in African donors with CGGn < 26 in comparison to African donors with CGGn greater or equal to 26 (P = 0.019), and Caucasian (P = 0.017) and Asian donors (P = 0.025) with CGGn < 26.
CONCLUSIONS
CGGn on FMR1 already at young ages affects FOR, but is clinically apparent only in cases of PDFOR. Screening for low FMR1 CGGn < 26 at young age, thus, appears predictive of later PDFOR.
背景
鉴于推测年轻时冗余的功能性卵巢储备（FOR）可能在临床上掩盖过早出现的卵巢储备功能减退（PDFOR），我们在年轻的卵母细胞捐献者中研究了FMR1基因的基因型和亚基因型，这些在之前的研究中与特定的卵巢衰老模式相关，并确定它们在如此年轻的年龄是否已经与卵巢储备（OR）的变化有关。我们还研究了这些捐献者中种族以及FMR1与初潮年龄的关联。
方法
在一项队列研究中，我们调查了157名卵母细胞捐献候选者，并根据抗苗勒管激素（AMH）的95%置信区间，将他们分为正常年龄特异性组（AMH大于或等于2.1 ng/mL；n = 121）和PDFOR组（AMH < 2.1 ng/mL；n = 36）。然后我们评估了FMR1基因上三核苷酸重复序列（CGGn）的数量与FOR（基于抗苗勒管激素，AMH）之间的关联。
结果
总体而言，FMR1与AMH无关。在36名患有PDFOR的捐献者中，17名（42%）至少有一个低（CGGn < 26）等位基因。其余FOR正常的捐献者中，CGGn大于或等于26的比例显著更高（73.6%对26.4%；P = 0.024），且AMH更高（P = 0.012）。这一发现主要是FMR1（CGGn < 26与CGGn大于或等于26）与种族之间相互作用的结果（P = 0.013），其中亚洲人影响最大（P = 0.009）。初潮年龄在FOR正常的捐献者中既与种族无关，也与FMR1状态无关。在患有PDFOR的捐献者中，种族与CGGn在统计学上相关（P = 0.018），这种关联主要基于与CGGn大于或等于26的非洲捐献者相比，CGGn < 26的非洲捐献者初潮年龄显著延迟（P = 0.019），以及与CGGn < 26的白种人（P = 0.017）和亚洲捐献者（P = 0.025）相比。
结论
FMR1上的CGGn在年轻时就影响FOR，但仅在PDFOR病例中在临床上明显。因此，在年轻时筛查低FMR1 CGGn < 26似乎可预测后期的PDFOR。
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