Reconstituted ovaries self-assemble without an ovarian surface epithelium

Enrique Sosa; Sinthia Kabir Mumu; Christian C Alvarado; Qiu Ya Wu; Isaias Roberson; Alejandro Espinoza; Fei-Man Hsu; Kaori Saito; Timothy J Hunt; Jared E Faith; Matthew G Lowe; Jonathan A DiRusso; Amander T Clark

doi:10.1016/j.stemcr.2023.10.001

Reconstituted ovaries self-assemble without an ovarian surface epithelium

Stem Cell Reports. 2023 Nov 14;18(11):2190-2202. doi: 10.1016/j.stemcr.2023.10.001. Epub 2023 Oct 26.

Authors

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Reproductive Science, Health and Education, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences - The Collaboratory, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Reproductive Science, Health and Education, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.

Abstract

Three-dimensional (3D) stem cell models of the ovary have the potential to benefit women's reproductive health research. One such model, the reconstituted ovary (rOvary) self-assembles with pluripotent stem cell-derived germ cells creating a 3D ovarian mimic competent to support the differentiation of functional oocytes inside follicles. In this study, we evaluated the cellular composition of the rOvary revealing the capacity to generate multiple follicles surrounded by NR2F2+ stroma cells. However, the rOvary does not develop a surface epithelium, the source of second-wave pre-granulosa cells, or steroidogenic theca. Therefore, the rOvary models represent the self-assembly of activated follicles in a pre-pubertal ovary poised but not yet competent for hormone production.

Keywords: follicles; germ cells; iPSCs; ovary; reconstituted ovary; self-assembly.

MeSH terms

Epithelium
Female
Granulosa Cells / metabolism
Humans
Oocytes
Ovarian Follicle*
Ovary* / metabolism

Abstract

MeSH terms

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