Universidade do Oeste Paulista, Presidente Prudente, São Paulo, Brazil.
Departamento de Farmacologia, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Mol Reprod Dev. 2019 Nov;86(11):1694-1704. doi: 10.1002/mrd.23259. Epub 2019 Aug 29.
Insulin-like growth factor 1 (IGF-1) activity is established by the regulation of IGF binding protein activity, which blocks IGF-1 functions, whereas pregnancy-associated plasma protein-A (PAPP-A) improves IGF-1 bioavailability and facilitates binding to IGF receptors. To further extend our understanding of the effect of exogenous PAPP-A on bovine embryo production, we added this protein during in vitro maturation of cumulus-oocyte complexes (COCs); moreover, we assessed its effects on IGF-1 quantity in the maturation medium, embryonic yield and postwarming survival, blastocyst quality, and transcript abundance. Bovine COCs were matured in a serum-free medium, either with PAPP-A supplementation (100 ng/ml) or without (control). The treatment group produced higher IGF-1 concentrations in the maturation medium; however, showed no difference on cleavage, blastocysts rates, and embryonic survival 3 and 24 hr postcryopreservation. Regarding gene expression, VNN1 was upregulated, whereas AGPAT9, FASN, EGFR, HAS2, and IMPDH1 were downregulated in PAPP-A treated. PAPP-A treated, CPT2, DNMT3A, and TFAM were upregulated, whereas ATF4 and IFITM3 were downregulated. We concluded that although the addition of PAPP-A did not affect embryo yield and blastocyst survival, higher IGF-1 levels may affect embryo competence through differential expression of genes involved in lipid metabolism, oocyte competence, and mitochondrial function.
胰岛素样生长因子 1(IGF-1)的活性由 IGF 结合蛋白活性的调节所建立,IGF 结合蛋白会阻断 IGF-1 的功能,而妊娠相关血浆蛋白-A(PAPP-A)则可提高 IGF-1 的生物利用度并促进其与 IGF 受体结合。为了进一步深入了解外源性 PAPP-A 对牛胚胎生产的影响,我们在卵丘-卵母细胞复合物(COC)的体外成熟过程中添加了这种蛋白;此外,我们评估了其对成熟培养基中 IGF-1 数量、胚胎产量和冻融后存活、囊胚质量和转录丰度的影响。牛 COC 在无血清培养基中成熟,分为添加 PAPP-A(100ng/ml)组和不添加(对照组)。处理组在成熟培养基中产生的 IGF-1 浓度较高;然而,在卵裂率、囊胚率和冻融后 3 小时和 24 小时的胚胎存活率方面没有差异。关于基因表达,VNN1 上调,而 AGPAT9、FASN、EGFR、HAS2 和 IMPDH1 在 PAPP-A 处理下下调。CPT2、DNMT3A 和 TFAM 在 PAPP-A 处理下上调,而 ATF4 和 IFITM3 下调。我们得出结论,尽管添加 PAPP-A 并未影响胚胎产量和囊胚存活率,但较高的 IGF-1 水平可能通过影响参与脂质代谢、卵母细胞能力和线粒体功能的基因的差异表达来影响胚胎能力。