In vitro germ cell induction from fertile and infertile monozygotic twin research participants

Erica C Pandolfi; Fei-Man Hsu; Mark Duhon; Yi Zheng; Sierra Goldsmith; Jianping Fu; Sherman J Silber; Amander T Clark

doi:10.1016/j.xcrm.2022.100782

In vitro germ cell induction from fertile and infertile monozygotic twin research participants

Cell Rep Med. 2022 Oct 18;3(10):100782. doi: 10.1016/j.xcrm.2022.100782.

Authors

Erica C Pandolfi¹, Fei-Man Hsu¹, Mark Duhon², Yi Zheng³, Sierra Goldsmith⁴, Jianping Fu⁵, Sherman J Silber⁴, Amander T Clark⁶

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
² Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁴ Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, MO, USA.
⁵ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁶ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: clarka@ucla.edu.

Abstract

Human induced pluripotent stem cells (hiPSCs) enable reproductive diseases to be studied when the reproductive health of the participant is known. In this study, monozygotic (MZ) monoamniotic (MA) twins discordant for primary ovarian insufficiency (POI) consent to research to address the hypothesis that discordant POI is due to a shared primordial germ cell (PGC) progenitor pool. If this is the case, reprogramming the twin's skin cells to hiPSCs is expected to restore equivalent germ cell competency to the twins hiPSCs. Following reprogramming, the infertile MA twin's cells are capable of generating human PGC-like cells (hPGCLCs) and amniotic sac-like structures equivalent to her fertile twin sister. Using these hiPSCs together with genome sequencing, our data suggest that POI in the infertile twin is not due to a genetic barrier to amnion or germ cell formation and support the hypothesis that during gestation, amniotic PGCs are likely disproportionately allocated to the fertile twin with embryo splitting.

Keywords: amnion cells; discordant POI; embryo model; germ cells; hiPSCs; twins.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Amnion
Embryo, Mammalian
Female
Germ Cells
Humans
Induced Pluripotent Stem Cells*
Infertility*
Twins, Monozygotic / genetics

Abstract

Publication types

MeSH terms

Grants and funding