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Home / Equine Research Bank / Endocrinology / Pregnancy-associated plasma protein-A (PAPP-A) in ovine, bov...
Endocrinology2001; 142(12); 5243-5253; doi: 10.1210/endo.142.12.8517

Pregnancy-associated plasma protein-A (PAPP-A) in ovine, bovine, porcine, and equine ovarian follicles: involvement in IGF binding protein-4 proteolytic degradation and mRNA expression during follicular development.

Abstract: IGF binding protein-4 (IGFBP-4) proteolytic degradation is a common feature of preovulatory follicles from human, ovine, bovine, porcine, and equine ovary. In all these species, the protease is a zinc-dependent metalloprotease and its ability to degrade IGFBP-4 is IGF dependent. The human intrafollicular IGFBP-4-degrading protease has recently been identified as pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to investigate whether PAPP-A is also involved in IGFBP-4 degradation in ovine, bovine, porcine, and equine preovulatory follicles and to study the expression of PAPP-A mRNA in bovine and porcine granulosa cells from different classes of follicles. Immunoneutralization and immunoprecipitation with polyclonal antibodies raised against human PAPP-A inhibited IGFBP-4 proteolytic degradation in preovulatory follicular fluid from the four species studied. As previously reported for the intrafollicular proteolytic activity degrading IGFBP-4, recombinant human PAPP-A generated in vitro 17- and 10-kDa IGFBP-4-proteolytic fragments. Recombinant PAPP-A activity was also shown to be IGF dependent and was inhibited by heparin-binding domain-containing peptides. In all mammalian species studied, the PAPP-A sequences showed high degree of identity. Moreover, the PAPP-A gene was localized on porcine chromosome 1 (1q29-1q213), in agreement with the localization of human PAPP-A gene on human chromosome 9q33.1. In bovine and porcine ovaries, real-time quantitative RT-PCR showed that PAPP-A mRNA expression in granulosa cells was maximal in fully differentiated follicles and was positively correlated with expression of P450 aromatase and LH receptor mRNAs. Overall, these data show that PAPP-A is responsible for IGFBP-4 degradation in ovine, bovine, porcine, and equine preovulatory follicles. The high expression of PAPP-A mRNA in granulosa cells from large, differentiated follicles suggest that it is a new functional marker of follicular development.
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Publication Date: 2001-11-20 PubMed ID: 11713222DOI: 10.1210/endo.142.12.8517Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research investigates the role of pregnancy-associated plasma protein-A (PAPP-A) in the degradation of IGF binding protein-4 (IGFBP-4) within ovarian follicles of several animal species. It also studies mRNA expression of PAPP-A during follicular development.

Research Objective and Methodology

  • The main goal of the research was to study PAPP-A’s involvement in IGFBP-4 degradation in preovulatory follicles of ovine, bovine, porcine, and equine species. Furthermore, the researchers sought to analyze the expression of PAPP-A mRNA in bovine and porcine granulosa cells from various follicle classes.
  • The researchers used immunoneutralization and immunoprecipitation methods with polyclonal antibodies raised against human PAPP-A to study the proteolytic degradation of IGFBP-4 in preovulatory follicular fluid across the four species being examined.
  • Recombinant human PAPP-A was generated in vitro to study the proteolytic activity and the resulting fragments of IGFBP-4.
  • IGF dependence and inhibition by heparin-binding domain-containing peptides of recombinant PAPP-A activity was also studied.
  • The researchers employed real-time quantitative RT-PCR to analyze the expression of PAPP-A mRNA in granulosa cells in bovine and porcine ovaries.

Research Findings

  • The researchers found that antibodies against human PAPP-A inhibited IGFBP-4 proteolytic degradation in preovulatory follicular fluid across all four species studied.
  • It was also discovered that recombinant human PAPP-A generated 17- and 10-kDa IGFBP-4-proteolytic fragments synonymous with the intrafollicular proteolytic activity previously observed.
  • The research found that the activity of recombinant PAPP-A was IGF-dependent and could be inhibited by heparin-binding domain-containing peptides.
  • The PAPP-A gene was identified on porcine chromosome 1, a location similar to the human PAPP-A gene’s location on human chromosome 9q33.1, indicating a high degree of identity in PAPP-A sequences across species.
  • Mature follicles demonstrated the highest levels of PAPP-A mRNA expression, with a positive correlation found between this expression and the expression of P450 aromatase and LH receptor mRNA.

Implications of Research

  • The findings of this research confirm that PAPP-A is responsible for IGFBP-4 degradation in ovine, bovine, porcine, and equine preovulatory follicles. This agrees with previous findings about human intrafollicular IGFBP-4-degrading activity.
  • The study suggests that PAPP-A mRNA could be a novel functional marker for follicular development due to its high expression in granulosa cells from large, differentiated follicles. This could be beneficial in reproductive biology and veterinary medicine for monitoring ovarian follicular development.

Cite This Article

APA
Mazerbourg S, Overgaard MT, Oxvig C, Christiansen M, Conover CA, Laurendeau I, Vidaud M, Tosser-Klopp G, Zapf J, Monget P. (2001). Pregnancy-associated plasma protein-A (PAPP-A) in ovine, bovine, porcine, and equine ovarian follicles: involvement in IGF binding protein-4 proteolytic degradation and mRNA expression during follicular development. Endocrinology, 142(12), 5243-5253. https://doi.org/10.1210/endo.142.12.8517

Publication

Endocrinology
ISSN: 0013-7227
NlmUniqueID: 0375040
Country: United States
Language: English
Volume: 142
Issue: 12
Pages: 5243-5253

Researcher Affiliations

Mazerbourg, S
  • Physiologie de la Reproduction et des Comportements, Université F. Rabelais de Tours, 37380 Nouzilly, France.
Overgaard, M T
    Oxvig, C
      Christiansen, M
        Conover, C A
          Laurendeau, I
            Vidaud, M
              Tosser-Klopp, G
                Zapf, J
                  Monget, P

                    MeSH Terms

                    • Amino Acid Sequence / genetics
                    • Animals
                    • Aromatase / genetics
                    • Base Sequence / genetics
                    • Cattle
                    • Chromosome Mapping
                    • DNA, Complementary / genetics
                    • Female
                    • Follicular Fluid / metabolism
                    • Follicular Phase / physiology
                    • Granulosa Cells / metabolism
                    • Horses
                    • Humans
                    • Insulin-Like Growth Factor Binding Protein 4 / metabolism
                    • Molecular Sequence Data
                    • Ovarian Follicle / physiology
                    • Peptide Hydrolases / metabolism
                    • Pregnancy-Associated Plasma Protein-A / genetics
                    • Pregnancy-Associated Plasma Protein-A / physiology
                    • RNA, Messenger / metabolism
                    • Receptors, LH / genetics
                    • Recombinant Proteins
                    • Sheep
                    • Swine

                    Citations

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