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Effect of intra-ovarian injection of mesenchymal stem cells in aged mares

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

This study aims to determine if intra-ovarian injection of bone marrow–derived mesenchymal stem cells (MSCs) improves or restores ovarian function in aged females.

Methods

Prospective randomized study of eight aged mares and six young mares receiving intra-ovarian injection of MSCs or vehicle. Main outcome measures were antral follicle count and serum anti-Müllerian hormone (AMH) (aged and young mares), and for aged mares, oocyte meiotic and developmental competence; gross and histological ovarian assessment; evaluation of presence of chimerism in recovered granulosa cells and in ovarian tissue samples; and gene expression in ovarian tissue as assessed by RNA sequencing.

Results

Injection of MSCs was not associated with significant changes in follicle number, oocyte recovery rate on follicle aspiration, oocyte maturation rate, or blastocyst rate after ICSI in aged mares, or in changes in follicle number in young mares. There were no significant changes in peripheral AMH concentrations, indicating a lack of effect on growing follicles. MSC donor DNA was not recovered in granulosa cells or in ovarian tissue, indicating lack of persistence of injected MSC. RNA sequencing revealed significant differences in gene expression between MSC- and vehicle-injected ovaries.

Conclusions

Intra-ovarian injection of bone marrow–derived MSCs altered gene expression but did not improve ovarian function in aged mares.

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Acknowledgments

The authors thank Dr. Andrew Hillhouse for his help with RNA isolation; Dr. Gus Wright for his help with flow cytometry analyses; Dr. Young Ho Choi for performing ICSI on the recovered oocytes; Hsing Fann for her help with MSC culture, freezing, and thawing for intra-ovarian injections; and Angel del Valle for his help with mtDNA sequencing. The authors acknowledge Texas A&M Institute for Genome Sciences and Society (TIGSS) for providing computational resources for RNA-Seq data analysis and systems administration support for the TIGSS HPC Cluster.

Funding

Funded by the Clinical Equine ICSI Program at Texas A&M University, the Link Equine Research Fund at Texas A&M University, and a Postdoctoral Trainee Research Grant and a Graduate Student Core Facility Experiential Learning Program Grant from the College of Veterinary Medicine and Biomedical Sciences. S.T.G. was funded in part by a Texas A&M College of Veterinary Medicine & Biomedical Sciences Merit Scholars Fellowship.

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Authors and Affiliations

  1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843-4466, USA

    Sicilia T. Grady & Katrin Hinrichs

  2. Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843-4475, USA

    Ashlee E. Watts, James A. Thompson & Katrin Hinrichs

  3. Veterinary Genetics Laboratory, University of California, Davis, CA, 95616, USA

    M. Cecilia T. Penedo

  4. Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX, 77843, USA

    Kranti Konganti

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  1. Sicilia T. Grady
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  4. M. Cecilia T. Penedo
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Correspondence to Katrin Hinrichs.

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Grady, S.T., Watts, A.E., Thompson, J.A. et al. Effect of intra-ovarian injection of mesenchymal stem cells in aged mares. J Assist Reprod Genet 36, 543–556 (2019). https://doi.org/10.1007/s10815-018-1371-6

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  • DOI: https://doi.org/10.1007/s10815-018-1371-6

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