Balla Agneta, Danilovich Natalia, Yang Yinzhi, Sairam M Ram
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montréal, Québec, Canada H2W 1R7.
Biol Reprod. 2003 Oct;69(4):1281-93. doi: 10.1095/biolreprod.103.015552. Epub 2003 Jun 11.
Adult Follitropin Receptor Knockout (FORKO) female mice are infertile and estrogen deficient. In order to understand the peri/postnatal developmental changes, we have now characterized the structural and molecular aberrations by comparing several markers of follicular development in 2-, 10-, and 24-day-old wild-type and FORKO females. By Day 24, FORKO mice have 40%-50% smaller uteri and vaginas. Estradiol is undetectable but testosterone and LH levels are already elevated at this age. FORKO ovaries are 45% smaller, indicating a postnatal or perinatal deficit consequent to FSH receptor ablation. This is attributable to decreased numbers of growing follicles and reduced diameter. Developmental markers, such as Müllerian inhibiting substance, GATA-4, estrogen receptor beta, and androgen receptor, were differentially expressed in granulosa cells. In the 2-day-old mutant neonates, a faster recruitment process was noted that later slowed down, impeding development of follicles. This is noteworthy in light of the controversy regarding the direct role of FSH/receptor system as a determinant of small and preantral follicle development in rodents. As the pool of nongrowing primordial follicles specifies the duration of female fertility and timing of reproductive senescence, we believe that the postnatal FORKO female mouse could help in exploring the signals that impact on early folliculogenesis. In addition, our data suggest that the FSH/receptor system is a major contributor to the formation and recruitment of the nongrowing pool of follicles as early as Postnatal Day 2 in the mouse.
成年促卵泡激素受体基因敲除（FORKO）雌性小鼠不育且雌激素缺乏。为了解围产期/产后的发育变化，我们通过比较2日龄、10日龄和24日龄野生型及FORKO雌性小鼠卵泡发育的多个标志物，对其结构和分子异常进行了表征。到24日龄时，FORKO小鼠的子宫和阴道小40%-50%。此时无法检测到雌二醇，但睾酮和促黄体生成素水平已经升高。FORKO小鼠的卵巢小45%，表明促卵泡激素受体缺失导致出生后或围产期发育缺陷。这归因于生长卵泡数量减少和直径减小。发育标志物，如苗勒氏管抑制物质、GATA-4、雌激素受体β和雄激素受体，在颗粒细胞中差异表达。在2日龄的突变新生小鼠中，观察到卵泡募集过程加快，随后减慢，阻碍了卵泡发育。鉴于促卵泡激素/受体系统作为啮齿动物中小卵泡和窦前卵泡发育决定因素的直接作用存在争议，这一点值得注意。由于非生长型原始卵泡库决定了雌性生育期的长短和生殖衰老的时间，我们认为出生后的FORKO雌性小鼠有助于探索影响早期卵泡发生的信号。此外，我们的数据表明，促卵泡激素/受体系统早在小鼠出生后第2天就是非生长型卵泡库形成和募集的主要促成因素。
