posted on 2023-03-16, 14:35authored byXinyang Zhao, Siwen Zhang, Shan Gao, Hsun-Ming Chang, Peter C. K. Leung, Jichun Tan
Tissue engineering advancements have made it possible
to modify
biomaterials to reconstruct a similar three-dimensional structure
of the extracellular matrix (ECM) for follicle development and to
supply the required biological signals. We postulated that an artificial
polysaccharide hydrogel modified with an ECM mimetic peptide may produce
efficient irritation signals by binding to specific integrins providing
a suitable environment for follicular development and influencing
the behavior of human granulosa cells (hGCs). Laminin, an important
component of the extracellular matrix, can modulate hGCs and oocyte
growth. Specifically, follicles of mice were randomly divided into
two-dimensional (2D) and three-dimensional (3D) culture systems established
by a hydrogel modified with RGD or laminin mimetic peptides (IKVAV
and YIGSR) and RGD (IYR). Our results showed that 3D cultured systems
significantly improved follicle survival, growth, and viability. IYR
peptides enhanced the oocyte meiosis competence. Additionally, we
explored the effect of 3D culture on hGCs, which improved hGCs viability,
increased the proportion of S- and G2/M-phase cells, and inhibited
cell apoptosis of hGCs. On days 1 and 2, the secretion of progesterone
was reduced in 3D-cultured hGCs. Notably, 3D-cultured hGCs exhibited
delayed senescence, decreased oxidative stress, and elevated mitochondrial
membrane potential. Moreover, the expression levels of cumulus expansion-related
genes (COX2, HAS2, and PTX3) and integrin α6β1 were upregulated
in 3D-cultured hGCs. In conclusion, a 3D culture utilizing hydrogels
modified with Laminin-mimetic peptides can provide a durable physical
environment suitable for follicular development. The laminin-mimetic
peptides may regulate the biological activity of hGCs by attaching
to the integrin α6β1.