Fowler Paul A, Flannigan Samantha, Mathers Anna, Gillanders Kim, Lea Richard G, Wood Maureen J, Maheshwari Abha, Bhattacharya Siladitya, Collie-Duguid Elaina S R, Baker Paul J, Monteiro Ana, O'Shaughnessy Peter J
Division of Applied Medicine, Centre for Reproductive Endocrinology and Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
J Clin Endocrinol Metab. 2009 Apr;94(4):1427-35. doi: 10.1210/jc.2008-2619. Epub 2009 Mar 3.
Primordial follicle formation dictates the maximal potential female reproductive capacity and establishes the ovarian reserve. Currently, little is known about this process in the human.
The aim of the study was to identify genes associated with the onset of human fetal primordial follicle formation in morphologically normal human fetuses.
We conducted an observational study of the female fetal gonad, comparing gene expression before and during primordial follicle formation.
The study was conducted at the Universities of Aberdeen, Glasgow, and Nottingham.
PATIENTS/PARTICIPANTS: Ovaries were collected from 51 morphologically normal human female fetuses of women undergoing elective termination of normal second trimester pregnancies.
We performed fetal ovarian transcript expression by Affymetrix array and quantitative RT-PCR and gene product expression and localization by Western blot and immunohistochemistry.
Five transcripts were down-regulated and 61 were up-regulated in ovaries from older fetuses (18-20 wk) in which primordial follicle formation had started compared with younger (15-16 wk) fetuses in which no primordial follicles were observed. The altered genes contribute to major functions, including gene expression, tissue morphology, and apoptosis, that are essential for ovarian development. NALP5, the most highly regulated transcript, is an oocyte-specific maternal effect gene that is regulated downstream of FIGLA.
NALP5 probably plays a key role in the onset of human primordial follicle formation and thus the establishment of ovarian reserve in women.
原始卵泡的形成决定了女性最大的生殖潜能，并建立了卵巢储备。目前，对于人类的这一过程知之甚少。
本研究旨在确定与形态正常的人类胎儿原始卵泡形成起始相关的基因。
我们对女性胎儿性腺进行了一项观察性研究，比较原始卵泡形成之前和期间的基因表达。
该研究在阿伯丁大学、格拉斯哥大学和诺丁汉大学进行。
患者/参与者：从51名接受正常妊娠中期选择性终止妊娠的女性的形态正常的人类女性胎儿中收集卵巢。
我们通过Affymetrix芯片和定量RT-PCR进行胎儿卵巢转录本表达，并通过蛋白质免疫印迹和免疫组织化学进行基因产物表达及定位。
与未观察到原始卵泡的较年轻（15 - 16周）胎儿相比，在已开始原始卵泡形成的较年长（18 - 20周）胎儿的卵巢中，5个转录本下调，61个上调。这些改变的基因参与了包括基因表达、组织形态和细胞凋亡等对卵巢发育至关重要的主要功能。调控程度最高的转录本NALP5是一种卵母细胞特异性母体效应基因，受FIGLA下游调控。
NALP5可能在人类原始卵泡形成起始以及女性卵巢储备的建立中起关键作用。
