Effect of pregnancy-associated plasma protein-A (PAPP-A) single-nucleotide polymorphisms on the level and activity of PAPP-A and the hormone profile in fluid from normal human small antral follicles

Jane Alrø Bøtkjær, Tanni Borgbo, Søren Kløverpris, Pernille Rimmer Noer, Claus Oxvig, Claus Yding Andersen

    6 Citationer (Scopus)

    Abstract

    OBJECTIVE: To reveal a possible relationship between two single nucleotide polymorphisms (SNPs) in PAPP-A-1224 (rs7020782) and 327 (rs12375498)-and the level and activity of PAPP-A in follicular fluid (FF) of human small antral follicles, and to analyze the intrafollicular hormone levels.

    DESIGN: Laboratory investigation.

    SETTING: University hospital.

    PATIENT(S): Fifty volunteer women who contributed a total of 210 samples of FF from normal small antral follicles.

    INTERVENTION(S): Genotyping and measurement of antigen levels of steroids, PAPP-A, stanniocalcin-2 (STC2), and antimüllerian hormone (AMH) plus activity of PAPP-A toward insulin-like growth factor binding protein 4 (IGFBP-4).

    MAIN OUTCOME MEASURE(S): Measurement of PAPP-A levels and hormones with enzyme-linked immunosorbent assay (ELISA) and PAPP-A activity toward radiolabeled IGFBP-4.

    RESULT(S): Women homozygous for the minor C allele of the 1224 SNP showed a statistically significantly lower level of PAPP-A protein and activity in FF compared with women carrying the major A allele. These women also displayed nonsignificant reduced levels of estradiol and increased levels of AMH and androgen. A statistically significant correlation between FF levels of PAPP-A activity and the molar ratio of PAPP-A/STC2 was obtained. The 327 SNP did not show statistically significant associations.

    CONCLUSION(S): This study presents a statistically significant effect of the 1224 SNP on the level and activity of PAPP-A in human follicles, suggesting that the FF level of bioactive insulin-like growth factor depends on the genotype. We observed STC2 to be an important regulator of PAPP-A in human FF. The 1224 SNP has previously been associated with recurrent pregnancy loss, so further evaluation of an underlying mechanism including aberrant control of insulin-like growth factor activity is warranted.

    OriginalsprogEngelsk
    TidsskriftFertility and Sterility
    Sider (fra-til)1778-1786
    Antal sider8
    ISSN0015-0282
    DOI
    StatusUdgivet - 25 okt. 2016

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