Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 38 min ago
Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Early-stage follicle development regulated by RGD peptide and ovarian fragment size in three-dimensional culture

  • Sandy Chen1,2
  • Cassandra Matsushige1
  • Lleyton Chen1
  • Makayla Horsley1
  • Margaux Mongue1
  • Alexandra Masca1
  • Michelle D. Tallquist3
  • Yukiko Yamazaki1
  1. 1Yanagimachi Institute for Biogenesis Research, Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa
  2. 2Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine
  3. 3Center for Cardiovascular Research, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa
Open at sourceDOICite

Abstract

The tripeptide Arg-Gly-Asp (RGD) is a minimal integrin-binding motif found in multiple extracellular matrix (ECM) proteins. We previously determined that immature ovarian fragments cultured in the RGD-immobilized dextran hydrogel significantly promoted antral follicle development compared to those cultured in the dextran hydrogel control. In this study, using neonatal mouse ovaries, we examined the effects of RGD peptide and ovarian fragment size on early-stage follicle development in our 3D culture system. One neonatal ovary was cut into 1/2, 1/4, or 1/8 fragments and cultured in the dextran hydrogel with or without RGD. Follicle development progressively increased as fragment size decreased (intact < 1/2 < 1/4 < 1/8). Notably, RGD treatment further enhanced follicle development in a size-dependent manner. In particular, the RGD-treated 1/8 fragments significantly promoted follicle development compared to all other groups with or without RGD. Previous studies have shown that ovarian fragmentation stimulates early-stage follicle development through disruption of the Hippo pathway. We found that the RGD treatment further increased the Hippo pathway disruption in the 1/8 fragments compared to those cultured without RGD. As a ligand, RGD binds to integrin receptors to induce various cell functions. In the neonatal ovary, ovary-specific RGD-binding integrins αvβ3 and αvβ5 were predominantly localized in the ovarian interstitial/theca cells. To evaluate the role of the RGD-integrin interaction, we blocked integrins αvβ3 and αvβ5 using Cilengitide (Ci). In the presence of Ci, RGD-induced follicle development and the Hippo pathway disruption were completely suppressed in the 1/8 fragments in 3D culture. These results suggest that the RGD-integrin interaction is crucial for promoting early-stage follicle development in 3D culture. Overall, our study demonstrates that ovarian fragment size significantly influences early-stage follicle development in culture. Fragmentation exposes the ovarian stromal compartment expressing RGD-binding integrins to the surrounding hydrogel. Moreover, the effect of RGD treatment on follicle development depends on ovarian fragment size in our 3D culture system, with 1/8 fragments yielding the greatest enhancement.

Related

  1. Katsuwonus pelamis heart hydrolysates promote hair growth in 3-dimensional human hair follicle organoids and in mice
    Hee Soo Kim, Eunyoung Lee, Do Yun Cho +3
    Food Science and BiotechnologyPeer-reviewedLicence not statedFull textGeneral medicinePMC
  2. Exposure to a mixture of long-chain PFAS disrupts ovarian follicle development, ovulation, and luteinization in female mice
    A. R. R. Caceres, J. Zhang, T. Costanza +3
    bioRxivPreprintAll rights reservedFull textPharmacology & toxicologybioRxiv
  3. MAPK Signaling Contributes to Primary Follicle Development in Zebrafish (Danio rerio).
    Guangjing Zhang, Jing Huang, Xiudan Yuan +7
    Animals : an open access journal from MDPIPeer-reviewedCC BYFull textPhysiologyEurope PMC
  4. Development and design rules for a modular human peptide-tag adaptor CAR T cell system
    A. H. Joechner, M. Mach, M. Yeh +6
    bioRxivPreprintAll rights reservedFull textOncologybioRxiv
  5. Thioredoxin‐Interacting Protein‐Regulated in Development and DNA Damage‐Response 1‐Driven Macrophage Senescence Promotes Hypoxia‐Induced Pulmonary Hypertension
    Yan Li, Tianfan Zhu, Donghai Lin +8
    Journal of the American Heart AssociationPeer-reviewedCC BY-NC-NDCardiovascular medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{chen2026earlystage,
  title = {{Early-stage follicle development regulated by RGD peptide and ovarian fragment size in three-dimensional culture}},
  author = {Sandy Chen and Cassandra Matsushige and Lleyton Chen and Makayla Horsley and Margaux Mongue and Alexandra Masca and Michelle D. Tallquist and Yukiko Yamazaki},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = nov,
  doi = {10.3389/fendo.2026.1996235},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1996235/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Early-stage follicle development regulated by RGD peptide and ovarian fragment size in three-dimensional culture
AU  - Sandy Chen
AU  - Cassandra Matsushige
AU  - Lleyton Chen
AU  - Makayla Horsley
AU  - Margaux Mongue
AU  - Alexandra Masca
AU  - Michelle D. Tallquist
AU  - Yukiko Yamazaki
PY  - 2026
DA  - 2026/11/06
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1996235
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1996235/full
AB  - The tripeptide Arg-Gly-Asp (RGD) is a minimal integrin-binding motif found in multiple extracellular matrix (ECM) proteins. We previously determined that immature ovarian fragments cultured in the RGD-immobilized dextran hydrogel significantly promoted antral follicle development compared to those cultured in the dextran hydrogel control. In this study, using neonatal mouse ovaries, we examined the effects of RGD peptide and ovarian fragment size on early-stage follicle development in our 3D culture system. One neonatal ovary was cut into 1/2, 1/4, or 1/8 fragments and cultured in the dextran hydrogel with or without RGD. Follicle development progressively increased as fragment size decreased (intact < 1/2 < 1/4 < 1/8). Notably, RGD treatment further enhanced follicle development in a size-dependent manner. In particular, the RGD-treated 1/8 fragments significantly promoted follicle development compared to all other groups with or without RGD. Previous studies have shown that ovarian fragmentation stimulates early-stage follicle development through disruption of the Hippo pathway. We found that the RGD treatment further increased the Hippo pathway disruption in the 1/8 fragments compared to those cultured without RGD. As a ligand, RGD binds to integrin receptors to induce various cell functions. In the neonatal ovary, ovary-specific RGD-binding integrins αvβ3 and αvβ5 were predominantly localized in the ovarian interstitial/theca cells. To evaluate the role of the RGD-integrin interaction, we blocked integrins αvβ3 and αvβ5 using Cilengitide (Ci). In the presence of Ci, RGD-induced follicle development and the Hippo pathway disruption were completely suppressed in the 1/8 fragments in 3D culture. These results suggest that the RGD-integrin interaction is crucial for promoting early-stage follicle development in 3D culture. Overall, our study demonstrates that ovarian fragment size significantly influences early-stage follicle development in culture. Fragmentation exposes the ovarian stromal compartment expressing RGD-binding integrins to the surrounding hydrogel. Moreover, the effect of RGD treatment on follicle development depends on ovarian fragment size in our 3D culture system, with 1/8 fragments yielding the greatest enhancement.
SN  - 1664-2392
ER  -