Related Experiment Video
Updated: Oct 26, 2025
A Modified Co-Culture System for Understanding Granulosa-Theca Cell Interactions in the Bovine Ovary
Published on: September 19, 2025
BMP6 increases CD68 expression by up-regulating CTGF expression in human granulosa-lutein cells
Xin-Yue Zhang1, Hsun-Ming Chang2, Yuyin Yi2
1Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, Jilin, China; Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
Bone morphogenetic protein 6 (BMP6) stimulates connective tissue growth factor (CTGF) and macrophage marker CD68 expression in human granulosa cells. This pathway involves BMP receptors ALK2/ALK3 and SMAD signaling, mediated by CTGF.
Area of Science:
- Reproductive Biology
- Cell Signaling
- Ovarian Physiology
Background:
- Bone morphogenetic protein 6 (BMP6) and connective tissue growth factor (CTGF) are vital for ovarian function.
- Cluster of Differentiation 68 (CD68) marks macrophages involved in corpus luteum regression.
Purpose of the Study:
- To investigate the effect of BMP6 on CTGF and CD68 expression in human granulosa cells.
- To elucidate the underlying molecular mechanisms of BMP6-induced CD68 expression.
Main Methods:
- In vitro experiments using primary and immortalized human granulosa cells (SVOG).
- Treatment with BMP6 and assessment of CTGF and CD68 expression levels.
- Utilized BMP type I receptor inhibitors (dorsomorphin, DMH-1, SB431542) and SMAD4/CTGF knockdown.
Main Results:
- BMP6 significantly increased CTGF and CD68 expression.
- BMP6-induced effects were mediated by activin receptor-like kinase (ALK)2 and ALK3.
- The canonical SMAD signaling pathway was essential for BMP6-induced CTGF and CD68 upregulation.
- CTGF knockdown abolished BMP6-induced CD68 expression, confirming CTGF's mediating role.
Conclusions:
- BMP6 promotes CTGF and CD68 expression in human granulosa cells.
- BMP6 signaling involves ALK2/ALK3 receptors and the SMAD pathway.
- Intrafollicular CTGF mediates BMP6-induced CD68 expression, highlighting a novel regulatory mechanism in ovarian physiology.
