P-543 Higher maternal age alters the insulin/IGF system and intracellular lipid metabolism of the endometrium and in the preimplantation embryo – insights from the rabbit model.

Abstract Study question Our aim was to analyse the embryo-maternal-interaction, focusing on insulin/IGF-system and lipid metabolism day 6 of pregnancy in reproductive young old rabbits. Summary answer Advanced maternal age has a decisive effect embryonic insulin/IGF-signalling metabolism, leading higher embryo loss already during preimplantation period. What is known The potential women declines with age. Molecular biochemical mechanisms involved age-related infertility their impact embryo-maternal-interaction early are still not completely understood. However, establishment successful depends physiological condition mother continuous dialogue developing embryo. plays pivotal role this embryo-maternal crosstalk, connecting insulin/IGF cell proliferation differentiation. design, size, duration We used rabbit as model investigate alterations Compared humans, shares high similarities development, gastrulation (DOI: 10.1530/REP-12-0091 DOI: 10.1093/ajcn/62.2.458S). A total 50 (16-20 weeks) 31 (<108 sexually mature, female rabbits were for analysis at post coitum. Participants/materials, setting, methods measured mRNA protein levels target genes system by quantitative PCR, Western Blot ELISA. Therefore, blood, endometrium blastocysts analysed from (16 20 (over 108 pregnancy. Blastocysts ovulation points counted only pre-gastrulating stage 1, separated embryoblast (EB) trophoblast (TB), further analyses. Main results chance At pregnancy, had lower amount embryos. Maternal serum insulin IGF reduced rabbits, accompanied paracrine upregulation IGF1 its receptors endometrium. Preimplantation adapted hormonal changes reducing IGF2 both compartments, EB TB, while expression unchanged. Furthermore, an increase fatty acids observed ageing endometrium, indicated level carnitine palmitoyltransferase I B (CPT1B) elevated acid binding transport proteins. These line synthesis (FASN) old, gravid key enzyme synthesis. Embryonic uptake b-oxidation increased too. caused transcription factors cAMP-responsive element (CREB) peroxisome proliferator-activated receptor (PPAR) α γ embryos Limitations, reasons caution Rabbit embryogenesis reflects human development formation. statements limited stages investigated. Wider implications findings current study accordance common literature, showing that advanced affects developmental competence out alters insulin/IGF-signalling, which two crucial components embryo-maternal-interaction. Trial registration number applicable