Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary
Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary
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DOI：
10.1677/joe-09-0109
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Pepling, Melissa E.
中科院分区：
文献类型：
--
作者：
Chen, Ying;Breen, Kelsey;Pepling, Melissa E.
在小鼠胚胎发育过程中，卵母细胞在生殖细胞包囊中发育，生殖细胞包囊由几轮细胞分裂和不完全胞质分裂形成。出生后不久，囊肿破裂，单个卵母细胞被颗粒细胞包裹形成原始卵泡。同时，三分之二的卵母细胞死于凋亡，只有三分之一的卵母细胞存活。我们以前已经表明，类固醇激素，雌二醇（E-2），孕酮以及植物雌激素染料木黄酮可以抑制囊肿破裂和原始卵泡组装。然而，类固醇激素调节卵母细胞包囊破裂和卵母细胞选择性存活的机制尚不清楚。在这里，我们证实了雌激素受体（ER）mRNA和蛋白质的表达在新生小鼠卵巢逆转录酶-PCR，免疫印迹和免疫细胞化学。然后，我们使用ER特异性激动剂和拮抗剂来了解雌激素信号传导的机制。ER α选择性激动剂4，4 '，4“-（4-丙基-[1H]-吡唑-1，3，5-三基）三酚和ER β选择性激动剂2，3-双（4-羟基苯基）-丙腈均抑制器官培养物中的囊肿破裂，表明E-2可通过两种受体发出信号以调节囊肿破裂。雌激素受体拮抗剂ICI 182，780可完全阻断E-2的作用。1，3-二（4-羟基苯基）-4-甲基-5-[4-（4-甲基-5-氧代苯基）氨基]-2-甲基-IH-吡唑（2-哌啶基乙氧基）苯酚]-1H-吡唑二盐酸盐（一种ER α特异性拮抗剂）完全阻断E-2对卵母细胞包囊破裂和原始卵泡组装的作用，（R，R）-5，11-二乙基-5，6，11，12-四氢-2，8-金鱼藻（一种ER β特异性拮抗剂）部分阻断E-2，这进一步支持了两种受体都参与新生卵母细胞发育中的雌激素信号传导的观点。结合BSA的E-2仅能在膜上发挥作用，但能抑制包囊破裂，这意味着E-2也可以通过膜结合的ER 2来调节包囊破裂。内分泌学杂志（2009）202，407-417
During mouse embryonic development, oocytes develop in germline cysts, formed by several rounds of cell division followed by incomplete cytokinesis. Shortly after birth, cysts break down and individual oocytes are enclosed by granulosa cells to form primordial follicles. At the same time, two-thirds of the oocytes die by apoptosis with only one-third surviving. We have previously shown that the steroid hormones, estradiol (E-2), and progesterone as well as the phytoestrogen genistein can inhibit cyst breakdown and primordial follicle assembly. However, the mechanisms by which steroid hormones regulate oocyte cyst breakdown and selective oocyte survival are unknown. Here, we confirmed the expression of estrogen receptor (ER) mRNA and protein in neonatal mouse ovaries using reverse transcriptase-PCR, western blotting, and immunocytochemistry. We then used ER-specific agonists and antagonists to understand the mechanism of estrogen signaling. 4,4',4 ''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, an ER alpha-selective agonist, and 2,3-bis (4-hydroxyphenyl)-propionitrile, an ER beta-selective agonist, both inhibited cyst breakdown in organ culture, suggesting that E-2 can signal through both the receptors to regulate cyst breakdown. ICI 182,780, an ER antagonist, completely blocked E-2's action. 1,3-bis (4-hydroxyphenyl)-4-methyl-5[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride, an ER alpha-specific antagonist, fully blocked E-2'S effect on oocyte cyst breakdown and primordial follicle assembly and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol, an ER beta-specifiic antagonist, partially blocked E-2, further supporting the idea that both receptors are involved in estrogen signaling in neonatal oocyte development. E-2 conjugated to BSA, which can only exert effects at the membrane, was able to inhibit cyst breakdown, implying that E-2 could also function through a membrane-bound ER2 to regulate cyst breakdown. journal of Endocrinology (2009) 202, 407-417