Successful fertilization depends upon proper cumulus-oocyte complex (COC) expansion. Synthesized by hyaluronan synthases (HASs), hyaluronan forms the backbone of the COC matrix and plays a critical role in COC expansion. This study investigated the effects and mechanisms of ovarian BMPs on HAS expression and hyaluronan production in human granulosa cells. Treatment with BMP4, BMP6, BMP7 or BMP15 induced differing levels of noncanonical SMAD2/3, but equal levels of canonical SMAD1/5/8, phosphorylation which were mirrored by differing levels of HAS2 up-regulation and hyaluronan production. The effects of BMP4 and BMP15 on HAS2 mRNA were partially reversed by knockdown of SMAD3, and blocked by knockdown of SMAD2+SMAD3 or SMAD4. BMP4-induced SMAD2/3 phosphorylation and HAS2 mRNA up-regulation were mediated by both BMP and activin/transforming growth factor-beta type I receptors. Our results suggest differential activation of noncanonical SMAD2/SMAD3 signaling by BMPs causes disproportionate induction of HAS2 expression and hyaluronan production in immortalized human granulosa cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
[1]Univ British Columbia, Child & Family Res Inst, Dept Obstet & Gynaecol, Room 317,950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada.
[2]Jilin Univ, Bethune Hosp 1, Ctr Reprod Med, Changchun 130021, Jilin, Peoples R China.
[3]Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Reprod Med, Hangzhou 310009, Zhejiang, Peoples R China.
(8.0+极速模式)