女性不孕是困扰医学界的一大难题，科学家一直在积极地寻求解决的办法。美国研究人员近日发现了将近350种与女性生育有关的基因，这大大有助于人们对不孕问题展开更加广泛而深入的研究。相关论文发表在9月份的《遗传学》（Genetics）上。
领导最新研究的是美国德州大学西南医学中心的Diego Castrillon和Teresa Gallardo。他们在小鼠身上展开研究，关注的重点是Foxo3基因，该基因能够调控卵巢滤泡（follicle）的活性。通常情况下，滤泡的激活是交叉进行的，所以卵巢里存在着不同发展阶段的滤泡。
研究人员发现，在缺失了Foxo3基因的雌性小鼠中，滤泡在产生之初是正常的，但是随后会在相同的时间被激活。这表明调控滤泡生长的基因在同一时间被开启了，这为检测它们提供了方便。
研究人员随后从实验小鼠卵巢中检测到了348种活跃基因，但在其它组织中并没有发现，表明了它们能够在滤泡的生长中起特定作用。
Castrillon表示，发现的这些基因中有一些已知与不孕有关，但大多数是先前未知的。研究人员从这些基因中随机挑选了几种，观测它们在人类卵巢中的表现，发现这些基因在人类卵巢发展的早期是具有活性的。
女性中大约有13%的人患有不孕，最常见的原因就是卵巢功能障碍。Castrillon表示，此次研究为我们提供了更多的可供研究的相关基因，有助于我们了解女性不孕的原因。虽然实验是在小鼠身上进行的，但在分子水平上，人类和小鼠的卵巢生物学是相似的。
Castrillon表示，下一步的研究重点将是，找出这些基因怎样彼此联系以控制滤泡的发展，并研究它们在导致女性不孕过程中发挥的作用。（科学网 梅进/编译）
原始出处:
Genetics, Vol. 177, 179-194, September 2007, Copyright © 2007
doi:10.1534/genetics.107.074823
Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse
Teresa D. Gallardo, George B. John, Lane Shirley, Cristina M. Contreras, Esra A. Akbay, J. Marshall Haynie, Samuel E. Ward, Meredith J. Shidler and Diego H. Castrillon1
Department of Pathology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072
1 Corresponding author: University of Texas Southwestern Medical Center, Department of Pathology, 6000 Harry Hines Blvd., Dallas, TX 75390-9072.
E-mail: diego.castrillon@utsouthwestern.edu
Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility.
