McNeilly J R, Saunders P T, Taggart M, Cranfield M, Cooke H J, McNeilly A S
Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh Center for Reproductive Biology, Scotland.
Endocrinology. 2000 Nov;141(11):4284-94. doi: 10.1210/endo.141.11.7764.
Within 2 days of birth, the mouse ovary is mainly composed of oocytes surrounded by a few pregranulosa cells forming primordial follicles that remain quiescent until they are recruited by intraovarian or other unknown factors to initiate growth of the oocyte and proliferation of the attendant granulosa cells. However, the role of the oocyte in this early development and organization of the follicle is poorly understood. The Dazl knockout (-/-) mouse in which there is total ablation of oocytes in fetal life has allowed us to address this issue. Ovaries from -/- females lack any follicular structure and have no cells positive for either Mullerian inhibiting factor or sulfated glycoprotein-1, indicating a lack of small follicles or corpora lutea. However, by immunocytochemistry, there are cells positive for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase, and aromatase, indicating the presence of steroidogenically active cells capable of producing estrogen. This was confirmed by the presence of hypertrophied uterine endometrium expressing both estrogen receptor alpha (ER alpha) and ER beta together with normal levels of plasma estradiol. In addition, these steroidogenically active cells contain ER beta, inhibin alpha, and betaB-subunits, and -/- mice have low measurable plasma inhibin A and B levels. The ovarian steroids and inhibins had no significant effect on either plasma or pituitary gonadotropin levels, with significantly (P < 0.01) lower LH and FSH in intact +/+ and +/- females. However, significantly (P < 0.05) increased plasma inhibin B together with significantly (P < 0.05) lower FSH were observed in the +/- females. In conclusion, our data showed that despite oocyte loss in fetal life, the adult ovaries contained steroidogenically active cells capable of producing estradiol and inhibin. Furthermore, in the +/- mice, the enhanced plasma inhibin B implies a role for Dazl protein within the oocyte either from more small follicles or increased inhibin B production from each follicle.
出生后2天内，小鼠卵巢主要由卵母细胞组成，周围有一些前颗粒细胞，形成原始卵泡，这些卵泡保持静止状态，直到被卵巢内或其他未知因素募集，从而启动卵母细胞的生长和伴随颗粒细胞的增殖。然而，卵母细胞在卵泡早期发育和组织形成中的作用仍知之甚少。Dazl基因敲除（-/-）小鼠在胎儿期卵母细胞完全缺失，这使我们能够解决这个问题。-/-雌性小鼠的卵巢缺乏任何卵泡结构，且没有抗苗勒管激素或硫酸化糖蛋白-1阳性细胞，表明缺乏小卵泡或黄体。然而，通过免疫细胞化学检测，存在3β-羟基类固醇脱氢酶、17α-羟化酶和芳香化酶阳性的细胞，表明存在能够产生雌激素的具有类固醇生成活性的细胞。子宫肥大的子宫内膜同时表达雌激素受体α（ERα）和ERβ以及正常水平的血浆雌二醇，证实了这一点。此外，这些具有类固醇生成活性的细胞含有ERβ、抑制素α和βB亚基，-/-小鼠的血浆抑制素A和B水平可测值较低。卵巢类固醇和抑制素对血浆或垂体促性腺激素水平均无显著影响，完整的+/+和+/-雌性小鼠的促黄体生成素（LH）和促卵泡生成素（FSH）显著（P<0.01）降低。然而，在+/-雌性小鼠中观察到血浆抑制素B显著（P<0.05）升高，同时FSH显著（P<0.05）降低。总之，我们的数据表明，尽管胎儿期卵母细胞缺失，但成年卵巢中仍含有能够产生雌二醇和抑制素的具有类固醇生成活性的细胞。此外，在+/-小鼠中，血浆抑制素B的增加意味着卵母细胞内的Dazl蛋白发挥了作用，这可能是由于更多的小卵泡或每个卵泡中抑制素B产生增加所致。
