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Molecular human reproduction2024; 30(9); gaae033; doi: 10.1093/molehr/gaae033

Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’.

Abstract: Assisted reproductive technologies are an emerging field in equine reproduction, with species-dependent peculiarities, such as the low success rate of conventional IVF. Here, the 'cumulome' was related to the developmental capacity of its corresponding oocyte. Cumulus-oocyte complexes collected from slaughterhouse ovaries were individually matured, fertilized by ICSI, and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS)-based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total of 1671 proteins and 612 metabolites were included in the quantifiable 'cumulome'. According to the development of the corresponding oocytes, three groups were compared with each other: not matured (NM; n = 18), cleaved (CV; n = 15), and blastocyst (BL; n = 19). CV and BL were also analyzed together as the matured group (M; n = 34). The dataset revealed a closer connection within the two M groups and a more distinct separation from the NM group. Overrepresentation analysis detected enrichments related to energy metabolism as well as vesicular transport in the M group. Functional enrichment analysis found only the KEGG pathway 'oxidative phosphorylation' as significantly enriched in the NM group. A compound attributed to ATP was observed with significantly higher concentrations in the BL group compared with the NM group. Finally, in the NM group, proteins related to degradation of glycosaminoglycans were lower and components of cumulus extracellular matrix were higher compared to the other groups. In summary, the study revealed novel pathways associated with the maturational and developmental competence of oocytes.
© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.
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Publication Date: 2024-09-17 PubMed ID: 39288330PubMed Central: PMC11444741DOI: 10.1093/molehr/gaae033Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This study investigates how the molecular composition of the cumulus cells surrounding equine oocytes (the ‘cumulome’) relates to the oocytes’ ability to mature and develop successfully.
  • Using advanced proteomics and metabolomics techniques, the researchers identified specific proteins and metabolites that correlate with oocyte maturation and early embryonic development after fertilization.

Introduction and Background

  • Assisted reproductive technologies (ART) are increasingly used in horse breeding but face challenges unique to equines, such as a low success rate with conventional in vitro fertilization (IVF).
  • Oocytes (egg cells) develop within structures called cumulus-oocyte complexes (COCs); the cumulus cells surrounding the oocyte provide support and reflect the oocyte’s developmental status.
  • The ‘cumulome’ describes the complete set of proteins and metabolites present in the cumulus cells, which could provide insights into oocyte quality and competence (maturation ability and developmental potential).

Methods

  • Cumulus-oocyte complexes were collected from ovaries obtained at slaughterhouses.
  • Individual oocytes were matured in vitro, then fertilized by intracytoplasmic sperm injection (ICSI), and cultured to observe their developmental fate.
  • After maturation, cumulus cells were separated and analyzed using:
    • Proteomics via label-free mass spectrometry (MS) using nano-high-performance liquid chromatography tandem MS (nano-HPLC MS/MS).
    • Metabolomics through ultra-performance liquid chromatography coupled with nano-electrospray ionization MS (UPLC-nanoESI MS).
  • A total of 1671 proteins and 612 metabolites were quantified in the cumulus cells.

Experimental Groups

  • Based on the oocyte developmental outcomes, three groups were formed:
    • Not Matured (NM): Oocytes that did not mature (n=18).
    • Cleaved (CV): Oocytes that fertilized and underwent cleavage division (n=15).
    • Blastocyst (BL): Oocytes that developed successfully into blastocysts (n=19).
  • A combined matured group (M) was also analyzed, which included both CV and BL (n=34).

Key Findings: Proteomic and Metabolomic Profiles

  • The proteomic and metabolomic profiles of the matured groups (CV and BL) were more similar to each other than to the not matured (NM) group, indicating distinct molecular signatures associated with maturation.
  • Enrichment analysis showed:
    • Matured groups had higher activity in pathways related to energy metabolism and vesicular transport, which are essential for cellular function and communication.
    • The Not Matured group uniquely exhibited significant enrichment only in the ‘oxidative phosphorylation’ KEGG pathway, suggesting impaired mitochondrial or energy function.
  • One metabolite related to ATP (adenosine triphosphate, the main cellular energy currency) was significantly more abundant in the BL group compared to NM, linking higher energy availability with better developmental potential.

Changes in Extracellular Matrix and Glycosaminoglycan Degradation

  • Proteins involved in the degradation of glycosaminoglycans (important components of the extracellular matrix) were lower in the NM group compared to matured groups.
  • Conversely, components of the cumulus extracellular matrix were higher in the NM group, possibly indicating less remodeling or maturation of the cumulus matrix which is necessary for oocyte competence.

Conclusions and Implications

  • The study identified specific molecular pathways and compounds in cumulus cells that correlate with oocyte maturation and developmental competence in horses.
  • Energy metabolism and vesicular transport seem to be critical for oocyte developmental success, while impaired oxidative phosphorylation may underlie maturation failure.
  • Alterations in the cumulus extracellular matrix composition and its remodeling enzymes are linked to maturational competence, highlighting the role of cumulus matrix dynamics in oocyte quality.
  • These findings can aid in improving assisted reproduction techniques by providing biomarkers to select higher-quality oocytes and potentially modifying culture conditions to enhance equine ART outcomes.

Cite This Article

APA
Walter J, Colleoni S, Lazzari G, Fortes C, Grossmann J, Roschitzki B, Laczko E, Naegeli H, Bleul U, Galli C. (2024). Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’. Mol Hum Reprod, 30(9), gaae033. https://doi.org/10.1093/molehr/gaae033

Publication

Molecular human reproduction
ISSN: 1460-2407
NlmUniqueID: 9513710
Country: England
Language: English
Volume: 30
Issue: 9
PII: gaae033

Researcher Affiliations

Walter, Jasmin
  • Clinic of Reproductive Medicine, Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Colleoni, Silvia
  • Avantea srl, Laboratory of Reproductive Technologies, Cremona, Italy.
Lazzari, Giovanna
  • Avantea srl, Laboratory of Reproductive Technologies, Cremona, Italy.
Fortes, Claudia
  • Functional Genomics Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
Grossmann, Jonas
  • Functional Genomics Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
  • Swiss Institute of Bioinformatics (SIB), Zurich, Switzerland.
Roschitzki, Bernd
  • Functional Genomics Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
Laczko, Endre
  • Functional Genomics Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
Naegeli, Hanspeter
  • Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Bleul, Ulrich
  • Clinic of Reproductive Medicine, Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Galli, Cesare
  • Avantea srl, Laboratory of Reproductive Technologies, Cremona, Italy.

MeSH Terms

  • Animals
  • Horses
  • Oocytes / metabolism
  • Oocytes / growth & development
  • Oocytes / cytology
  • Female
  • Cumulus Cells / metabolism
  • In Vitro Oocyte Maturation Techniques
  • Proteomics / methods
  • Blastocyst / metabolism
  • Blastocyst / cytology
  • Metabolomics / methods
  • Tandem Mass Spectrometry
  • Sperm Injections, Intracytoplasmic

Grant Funding

  • FK-13-062 / University of Zurich

Conflict of Interest Statement

The authors declare that they have no conflict of interest.

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Citations

This article has been cited 1 times.
  1. Samiec M. Molecular Mechanisms of Somatic Cell Cloning and Other Assisted Reproductive Technologies in Mammals: Which Determinants Have Been Unraveled Thus Far?-Current Status, Further Progress and Future Challenges. Int J Mol Sci 2024 Dec 21;25(24).
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