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

TY - JOUR

T1 - 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

AU - Bøtkjær, Jane Alrø

AU - Borgbo, Tanni

AU - Kløverpris, Søren

AU - Noer, Pernille Rimmer

AU - Oxvig, Claus

AU - Andersen, Claus Yding

N1 - Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.fertnstert.2016.09.008

DO - 10.1016/j.fertnstert.2016.09.008

M3 - Journal article

C2 - 27793387

SN - 1546-2501

VL - 106

SP - 1778-1786.e8

JO - Sexuality, Reproduction and Menopause

JF - Sexuality, Reproduction and Menopause

IS - 7

ER -