Laboratory of Applied Genetics, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Present: Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
J Reprod Dev. 2023 Oct 20;69(5):270-278. doi: 10.1262/jrd.2023-041. Epub 2023 Sep 19.
The signals of the transforming growth factor β (TGF-β) superfamily play a critical role in follicular development in mammals. ACVR1B/TGFBR1/ACVR1C receptors mediate the signaling of several TGF-β superfamily ligands in granulosa cells. Although the requirement for ACVR1B/TGFBR1/ACVR1C receptor signaling in follicular development has been confirmed using mutant mouse models, the detailed roles of the signaling in granulosa cell and oocyte development have not been clearly defined. In the present study, we examined the requirement for ACVR1B/TGFBR1/ACVR1C receptor signaling in granulosa cells using an in vitro growth culture of oocyte-granulosa cell complexes (OGCs) and SB431542, a potent inhibitor of the receptor signaling. Although cumulus-oocyte complexes isolated from the control OGCs were able to undergo cumulus expansion, those isolated from OGCs grown with the inhibitor were not competent, even in the presence of in vivo-grown oocytes. The diameter of the oocytes in the SB431542-treated OGCs was comparable with that of the control; however, these oocytes were not competent for complete meiotic maturation or preimplantation development. Therefore, ACVR1B/TGFBR1/ACVR1C receptor signaling is not required for oocytes to increase their volume but is essential for the normal development of cumulus cells and oocyte developmental competence.
转化生长因子 β（TGF-β）超家族的信号在哺乳动物的卵泡发育中起着关键作用。ACVR1B/TGFBR1/ACVR1C 受体介导几种 TGF-β 超家族配体在颗粒细胞中的信号转导。虽然使用突变小鼠模型已经证实了 ACVR1B/TGFBR1/ACVR1C 受体信号在卵泡发育中的必要性，但该信号在颗粒细胞和卵母细胞发育中的详细作用尚未明确界定。在本研究中，我们使用卵母细胞-颗粒细胞复合物（OGC）的体外生长培养和 SB431542（一种有效的受体信号抑制剂）来研究 ACVR1B/TGFBR1/ACVR1C 受体信号在颗粒细胞中的必要性。尽管从对照 OGC 分离的卵丘-卵母细胞复合体能够进行卵丘扩展，但从用抑制剂生长的 OGC 中分离的复合体即使在体内生长的卵母细胞存在的情况下也没有能力进行扩展。用 SB431542 处理的 OGC 中的卵母细胞直径与对照的相似；然而，这些卵母细胞不能完全进行减数分裂成熟或着床前发育。因此，ACVR1B/TGFBR1/ACVR1C 受体信号对于卵母细胞增加其体积不是必需的，但对于颗粒细胞和卵母细胞发育能力的正常发育是必需的。
