Hedgehog signaling regulates the basement membrane remodeling during folliculogenesis in the neonatal mouse ovary
Hedgehog signaling regulates the basement membrane remodeling during folliculogenesis in the neonatal mouse ovary
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Hedgehog信号调节新生小鼠卵巢卵泡发生过程中的基底膜重塑
DOI：
10.1007/s00441-020-03222-9
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发表时间：
2020
影响因子：
3.6
通讯作者：
Sato Tomomi
中科院分区：
文献类型：
--
作者：
Terauchi Karin J.;Miyagawa Shinichi;Iguchi Taisen;Sato Tomomi
在小鼠卵巢中，卵母细胞和体细胞之间的相互作用对于卵泡的发生和随后的卵泡发育是必不可少的。通过雌激素受体(ER)β作用的合成雌激素己烯雌酚(DES)可阻断卵母细胞与体细胞之间的相互作用，在一个卵泡中含有两个以上卵母细胞的多卵泡滤泡(PF)可在新生小鼠卵巢中被诱导。已知Hedgehog信号调节颗粒细胞增殖、膜细胞分化和卵泡生长。为探讨Hedgehog信号在早期卵泡发生和DES诱导卵巢早衰中的作用，将新生小鼠卵巢在Hedgehog信号抑制剂10μM环胺(CPA)存在或不存在的情况下培养，并将其移植到去卵巢成年小鼠的肾被膜下。器官培养的卵巢移植后，PFS的数量和发生率均显著增加。CPA可显著降低器官培养的卵巢组织中IV型前胶原α1(Col4a1)的表达，但DES对其无明显影响。在WT和ERβKO小鼠中，DES均能显著增加刺猬的两个配体，即沙漠刺猬(Dhh)和印度刺猬(Ihh)，以及刺猬相互作用蛋白(HHIP)的表达。因此，我们推测DES可以通过ERα影响这些基因的表达，但不是通过抑制Hedgehog信号。因此，PFS可由DES或CPA诱导，但诱导机制不同。我们的结果揭示了Hedgehog信号在卵泡发生过程中的基底膜重塑中的重要作用，甚至在卵泡膜细胞分化之前。
In the mouse ovary, interactions between oocytes and somatic cells are essential for folliculogenesis and subsequent follicle development. The polyovular follicle (PF), which contains more than two oocytes in a follicle, can be induced in the neonatal mouse ovary when interactions between oocytes and somatic cells are disrupted by agents such as the potent synthetic estrogen diethylstilbestrol (DES) acting through estrogen receptor (ER) β. Hedgehog signaling is known to regulate granulosa cell proliferation, thecal cell differentiation, and follicle growth. To investigate the role of hedgehog signaling in the early folliculogenesis and in PF induction by DES, neonatal mouse ovaries were cultured with or without 10 μM cyclopamine (CPA), an inhibitor of hedgehog signaling, and grafted under the kidney capsule of adult ovariectomized host mice. The number and the incidence of PFs were significantly increased in organ-cultured ovaries post-grafting. Expression of procollagen type IV, alpha 1 (Col4a1) in organ-cultured ovaries was significantly reduced by CPA, but not by DES. The expression of two hedgehog ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), and a target gene, Hedgehog interacting protein (Hhip), was significantly increased by DES both in WT and ERβ KO mice. Therefore, we infer that DES can affect expression of those genes through ERα but not via suppression of hedgehog signaling. Thus, PFs are induced by DES or CPA, but the induction mechanism is different. Our results revealed an important role of hedgehog signaling in basement membrane remodeling during folliculogenesis even before thecal cell differentiation.
雌性小鼠生殖细胞形成同步分裂的囊肿。
DOI：
10.1242/dev.125.17.3323
发表时间：
1998
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Pepling,ME;Spradling,AC
通讯作者：
Spradling,AC
雌激素受体β参与新生儿暴露于己烯雌酚的小鼠卵巢多卵泡的诱导
影响因子：
0.9
作者：
Kirigaya;A.;Kim;H.;Hayashi;S.;Chambon;P.;Watanabe;H.;Iguchi;T. & Sato;T.
通讯作者：
T.