title: 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.
authors.affiliation: Physiologie de la Reproduction et des Comportements, Université F. Rabelais de Tours, 37380 Nouzilly, France.
authors.forename: S
authors.initials: S
authors.lastname: Mazerbourg
authors.forename: M T
authors.initials: MT
authors.lastname: Overgaard
authors.forename: C
authors.initials: C
authors.lastname: Oxvig
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.forename: C A
authors.initials: CA
authors.lastname: Conover
authors.forename: I
authors.initials: I
authors.lastname: Laurendeau
authors.forename: M
authors.initials: M
authors.lastname: Vidaud
authors.forename: G
authors.initials: G
authors.lastname: Tosser-Klopp
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: P
authors.initials: P
authors.lastname: Monget
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001141:Aromatase / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002417:Cattle; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D005498:Follicular Phase / Q000502:physiology; D006107:Granulosa Cells / Q000378:metabolism; D006736:Horses; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D008969:Molecular Sequence Data; D006080:Ovarian Follicle / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D011974:Receptors, LH / Q000235:genetics; D011994:Recombinant Proteins; D012756:Sheep; D013552:Swine
chemical_list: D018076:DNA, Complementary; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D011974:Receptors, LH; D011994:Recombinant Proteins; D001141:Aromatase; D010447:Peptide Hydrolases; D011266:Pregnancy-Associated Plasma Protein-A