A combination of growth factors and cytokines alter preimplantation mouse embryo development, fetal development and gene expression profiles.

Kathryn H. Gurner,T. T. Truong,A. Harvey,D. Gardner

Published 2020 in Molecular human reproduction

ABSTRACT

Within the maternal tract, the preimplantation embryo is exposed to an array of growth factors and cytokines, most of which are absent from culture media used in clinical IVF. Whilst the addition of individual GFs and cytokines to embryo culture media can improve preimplantation mouse embryo development, there is a lack of evidence on the combined synergistic effects of growth factors and cytokines on embryo development and further fetal growth. Therefore, in this study the effect of a combined group of growth factors and cytokines on mouse preimplantation embryo development and subsequent fetal development and gene expression profiles was investigated. Supplementation of embryo culture media with an optimised combination of GFs and cytokines (0.05 ng/mL VEGF, 1 ng/mL PDGF, 0.13 ng/mL IGF1, 0.026 ng/mL IGF2, 1 ng/mL GCSF) had no effect on embryo morphokinetics but significantly increased trophectoderm cell number (P = 0.002) and total cell number (P = 0.0245). Treatment with this combination of GFs and cytokines also significantly increased blastocyst outgrowth area (P < 0.05) and, following embryo transfer, increased fetal weight (P = 0.027), crown-rump length (P = 0.017) and overall morphological development (P = 0.0273). RNA-seq analysis of IVF fetuses identified concurrent alterations to the transcriptional profiles of liver and placental tissues compared with in-vivo developed fetuses, while the GF and cytokine treated group displayed an increased level of transcriptional aberration than untreated cultured embryos. Together these data highlight the importance of balancing the actions of such factors for the regulation of normal development and emphasise the need for further studies investigating this prior to clinical implementation.

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