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International journal of molecular sciences2025; 26(12); 5495; doi: 10.3390/ijms26125495

Biphasic CAPA-IVM Improves Equine Oocyte Quality and Subsequent Embryo Development Without Inducing Genetic Aberrations.

Abstract: In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes by allowing the cytoplasm additional time to acquire essential components critical for optimal competency. This study aims to evaluate the effect of CAPA-IVM on equine oocyte quality and developmental competence. Immature cumulus-oocyte complexes (COCs) were retrieved from slaughterhouse ovaries and matured in vitro either in CAPA-IVM (short 6 h, long 24 h pre-maturation) or standard IVM. Mature oocytes from each group were analyzed for calcium-releasing potential ( = 52) and single-oocyte proteomics ( = 44), and embryo development ( = 229) was assessed after fertilization with piezo-drilled intracytoplasmic sperm injection (ICSI). Genetic analysis of developed blastocysts ( = 41) was performed to detect chromosomal aberrations. Our findings demonstrate that CAPA-IVM of equine COCs yields significantly higher maturation rates than controls. Moreover, short CAPA-IVM with six hours pre-maturation culture showed substantially higher embryo development potential than the control group (20/69 vs. 9/63, respectively). Genetic analysis revealed a high euploidy rate in equine blastocysts regardless of the maturation conditions. Live calcium imaging of the fertilized oocytes demonstrated that the majority of oocytes displayed non-continuous calcium oscillation patterns, irrespective of maturation conditions. Single-oocyte proteomics reveals a comparable proteomic landscape between mature oocytes subjected to short CAPA-IVM and standard IVM. However, we identified four enriched gene sets with positive enrichment scores after short CAPA-IVM, related to cytoskeleton regulation, ribosomal function, and cytosolic components. Our findings indicate that CAPA-IVM holds the potential to improve oocyte quality and competence in horses. However, further fine-tuning of culture conditions would benefit the effective use of these IVM systems. Moreover, given that the mare serves as an excellent model for human reproduction, the molecular trends identified in this study could provide valuable insights for advancing human artificial reproductive technologies.
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Publication Date: 2025-06-08 PubMed ID: 40564960PubMed Central: PMC12192595DOI: 10.3390/ijms26125495Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research evaluates the impact of a specific in-vitro maturation method, known as CAPA-IVM, on the quality and developmental competence of horse oocytes. The study reveals that this method improves oocyte quality and developmental potential without causing genetic abnormalities.

Research Background

In the world of assisted reproduction, in-vitro maturation (IVM) of oocytes is commonly used, especially in cases where prior hormonal stimulation is not advisable. The key challenge with this is that oocytes matured in a laboratory setting often don’t reach the level of developmental competence of those matured in a host organism. This research evaluates a particular IVM method known as Capacitation IVM (CAPA-IVM), which includes an additional pre-maturation step. The purpose of this step is to better synchronize the oocyte’s cytoplasmic and nuclear maturity by extending the time for cytoplasm to accrue essential components.

  • The study was carried out on immature cumulus-oocyte complexes (COCs) extracted from slaughterhouse ovaries.
  • The oocytes were matured in vitro through the CAPA-IVM technique with two forms of pre-maturation: a short 6-hour procedure and a longer 24-hour procedure. These were compared against standard IVM.
  • The matured oocytes from all three groups were subjected to several analyses: calcium-releasing potential, single-oocyte proteomics, and post-fertilization embryo development.
  • The developed blastocysts were genetically analyzed to detect chromosomal aberrations.

Key Findings

The study demonstrated that CAPA-IVM yielded significantly better maturation rates than the control samples. Furthermore, the shorter form of CAPA-IVM, with just six hours pre-maturation, showed considerably better embryo development potential than the control samples.

  • Importantly, the genetic analysis of the resulting blastocysts revealed a high rate of euploidy (normal number of chromosomes) regardless of the maturation conditions.
  • The majority of the fertilized oocytes exhibited non-continuous patterns of calcium oscillation, irrespective of the maturation technique used.
  • Proteomics analysis revealed essentially similar landscapes between mature oocytes from the short CAPA-IVM and the standard IVM, though four enriched gene sets were identified in the short CAPA-IVM, relating to cytoskeleton regulation, ribosomal function, and cytosolic components.

Implications of the Research

These findings suggest that CAPA-IVM could be a significant tool in improving the quality and developmental competency of oocytes. The evidence of high rates of euploidy indicates that this technique does not exacerbate genetic abnormalities. However, more adjustments and fine-tuning of the culture conditions may be required to make full, effective use of such IVM systems. Considering that the physiological characteristics of horse reproduction closely mirror that of humans, these findings could potentially provide valuable insights that could advance human artificial reproductive technologies.

Cite This Article

APA
Fakhar-I-Adil M, Angel-Velez D, Araftpoor E, Amin QA, Hedia M, Bühler M, Gevaert K, Menten B, Van Soom A, Chuva de Sousa Lopes SM, Stoop D, De Roo C, Smits K, Heindryckx B. (2025). Biphasic CAPA-IVM Improves Equine Oocyte Quality and Subsequent Embryo Development Without Inducing Genetic Aberrations. Int J Mol Sci, 26(12), 5495. https://doi.org/10.3390/ijms26125495

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 26
Issue: 12
PII: 5495

Researcher Affiliations

Fakhar-I-Adil, Muhammad
  • Ghent-Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Department of Human Structure and Repair, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Angel-Velez, Daniel
  • Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, 9820 Merelbeke, Belgium.
Araftpoor, Emin
  • VIB-UGent Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium.
  • Department of Biomolecular Medicine, Ghent University, 9052 Ghent, Belgium.
Amin, Qurratul Ain
  • Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, 9820 Merelbeke, Belgium.
Hedia, Mohamed
  • Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, 9820 Merelbeke, Belgium.
  • Theriogenology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Bühler, Marcel
  • VIB-UGent Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium.
  • Department of Biomolecular Medicine, Ghent University, 9052 Ghent, Belgium.
Gevaert, Kris
  • VIB-UGent Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium.
  • Department of Biomolecular Medicine, Ghent University, 9052 Ghent, Belgium.
Menten, Björn
  • Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Van Soom, Ann
  • Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, 9820 Merelbeke, Belgium.
Chuva de Sousa Lopes, Susana Marina
  • Department of Anatomy and Embryology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Stoop, Dominic
  • Department for Reproductive Medicine, Women's Clinic, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
De Roo, Chloë
  • Department for Reproductive Medicine, Women's Clinic, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Smits, Katrien
  • Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, 9820 Merelbeke, Belgium.
Heindryckx, Björn
  • Ghent-Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Department of Human Structure and Repair, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

MeSH Terms

  • Animals
  • Horses
  • Oocytes / metabolism
  • Oocytes / cytology
  • In Vitro Oocyte Maturation Techniques / methods
  • In Vitro Oocyte Maturation Techniques / veterinary
  • Female
  • Embryonic Development
  • Blastocyst / metabolism
  • Blastocyst / cytology
  • Chromosome Aberrations
  • Cumulus Cells / cytology
  • Cumulus Cells / metabolism
  • Sperm Injections, Intracytoplasmic
  • Natriuretic Peptide, C-Type / pharmacology

Grant Funding

  • BOF.STG.2021.0042.01 / Bijzonder Onderzoeksfonds
  • 1177425N / Research Foundation - Flanders
  • 2018000504 (GOA030-18 BOF) / Bijzonder Onderzoeksfonds (BOF)

Conflict of Interest Statement

The authors declare that they have no conflicts of interest.

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Citations

This article has been cited 1 times.
  1. Liu X, Lu J, Zeng J, An L, Tian J, Xi G. The Anti-Apoptotic Effect of C-Type Natriuretic Peptide and the Regulation of NPPC in Porcine Ovarian Granulosa Cells. Int J Mol Sci 2025 Oct 15;26(20).
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