Shimizu Takashi
Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
J Reprod Dev. 2006 Feb;52(1):23-32. doi: 10.1262/jrd.17072.
Ovarian follicular development in mammals is the complex process including endocrine, paracrine and autocrine. There is the development of four basic stages of ovarian follicles, i.e. the primordial, primary, secondary and tertiary or Graafian follicles. There are few blood vessels in the cortical area where primordial and primary follicles are assembled. The development of these follicles is stimulated by oocytes derived factor including growth differentiation factor 9 (GDF-9) or bone morphogenetic protein 15 (BMP-15). Porcine GDF-9 complementary DNA (cDNA) cloned, and then injected its gene into the ovary in gilts. The injection of porcine GDF-9 gene resulted in an increase in the number of primary, secondary and tertiary follicles, concomitant with a decrease in the number of primordial follicles, indicating that exogenous GDF-9 can promote early folliculogenesis in the porcine ovary. On the other hand, the development of antral follicles is associated with increased density of blood vessels within the theca cell layers surrounding the follicles. A recent study reported that vascular endothelial growth factor (VEGF) play an important role in the process of thecal angiogenesis during follicular development. To investigate whether additional induction of thecal angiogenesis would support subsequent follicular development, miniature gilts were directly injected VEGF gene into the ovary. Injection of VEGF gene increased the levels of mRNA expression of VEGF 120 and VEGF 164 isoforms in the granulosa cells and VEGF protein contents in the follicular fluid. The number of preovulatory follicles and the capillary density in the theca interna increased significantly in the ovaries injected with VEGF gene compared with those treated with eCG alone, indicating that the regulation of thecal angiogenesis during follicular development is a very important factor in the development of ovulatory follicles. This technique may be an innovative technique for enhanced induction of follicular development in the ovary through gene and hormonal treatment, which may lead to prevention of infertility caused by ovarian dysfunction.
哺乳动物的卵巢卵泡发育是一个复杂的过程，包括内分泌、旁分泌和自分泌。卵巢卵泡有四个基本发育阶段，即原始卵泡、初级卵泡、次级卵泡和三级卵泡或格拉夫卵泡。原始卵泡和初级卵泡所在的皮质区域血管较少。这些卵泡的发育受到卵母细胞衍生因子的刺激，包括生长分化因子9（GDF-9）或骨形态发生蛋白15（BMP-15）。克隆了猪GDF-9互补DNA（cDNA），然后将其基因注射到后备母猪的卵巢中。注射猪GDF-9基因导致初级、次级和三级卵泡数量增加，同时原始卵泡数量减少，这表明外源性GDF-9可以促进猪卵巢早期卵泡发生。另一方面，窦状卵泡的发育与卵泡周围膜细胞层内血管密度增加有关。最近的一项研究报道，血管内皮生长因子（VEGF）在卵泡发育过程中的膜细胞血管生成过程中起重要作用。为了研究额外诱导膜细胞血管生成是否会支持随后的卵泡发育，将微型后备母猪的卵巢直接注射VEGF基因。注射VEGF基因增加了颗粒细胞中VEGF 120和VEGF 164亚型的mRNA表达水平以及卵泡液中VEGF蛋白含量。与单独用eCG处理的卵巢相比，注射VEGF基因的卵巢中排卵前卵泡数量和内膜毛细血管密度显著增加，这表明卵泡发育过程中膜细胞血管生成的调节是排卵卵泡发育的一个非常重要的因素。这项技术可能是一种通过基因和激素治疗增强卵巢卵泡发育诱导的创新技术，这可能有助于预防卵巢功能障碍引起的不孕症。
