ESPE Abstracts (2015) 84 P-3-1254

Programming & Misc.

Untargeted Plasma Metabolomics in Prepubertal ICSI and Naturally Conceived Children Unravels Gender: Dimorphic Metabolic Trajectories After ICSI

Alexandra Gkourogiannia, Aristeidis G Telonisb, Ioanna Kosteriaa, Alexandra Margelic, Emilia Mantzoua, Maria Konstaa, Dimitrios Loutradisd, George Mastorakose, Ioannis Papassotiriouc, Christina Kanaka-Gantenbeina, MariaI Klapab & George P Chrousosa

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aDivision of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University Medical School, Athens, Greece; bMetabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; cDepartment of Clinical Biochemistry, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece; dDivision of In Vitro Fertilization, First Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece; eDivision of Endocrinology, Second Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece


Background: ICSI is an assisted reproduction technique (ART) mainly used to overcome male infertility. Nowadays, ICSI is employed frequently due to its high success rate, despite it being highly invasive (i.e. epigenetic risk). Recent studies in ART offspring show a higher incidence of cardio-metabolic risk than in naturally-conceived (NC) controls. Thus, in our prior untargeted metabolomic study between ICSI and NC prepubertal girls, we demonstrated insulin resistance in the former.

Aims and objectives: Untargeted plasma metabolomic analysis of ICSI and NC prepubertal boys was performed to detect possible gender-dimorphic metabolic differences with respect to the girl study group.

Methods: Blood plasma samples of strictly matched ICSI and NC boys were analysed by gas chromatography–mass spectrometry (GC–MS) metabolomics. Both metabolomic and biochemical data were analysed using multivariate statistics and compared with the corresponding results of the girl ICSI and NC groups. The results were visualized on a reconstructed inter-organ metabolic network.

Results: Combining metabolomic and biochemical measurements differentiated the ICSI and NC groups in both genders, with this difference being more prominent in the girls. However, the discriminatory metabolites were gender-specific. Whereas in both sexes a significantly higher concentration in insulin resistance associated metabolites was observed in the ICSI group, in the ICSI boys the largest difference relatively to the NC group was the significantly smaller concentration of the aromatic amino acids, potentially correlated with brain and liver abnormalities.

Conclusions: Our results suggest an increased risk for metabolic disorders as a result of ICSI in both boys and girls. By providing a high resolution perspective of the metabolic state in pre-pubertal children, metabolomics might help develop gender-specific tests and treatments.

Funding: Hellenic Endocrine Society.

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