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PLoS One. 2014 Apr 11;9(4):e94001. doi: 10.1371/journal.pone.0094001. eCollection 2014.

Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, University of Athens Medical School, Athens, Greece.
2
Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; Graduate Program "Biological Technology", Department of Biology, University of Patras, Greece.
3
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
4
Endocrine Unit, Department of Endocrinology and Metabolism, Evgenidion Hospital, Athens, Greece.
5
Division of In Vitro Fertilization, First Department of Obstetrics and Gynecology, University of Athens Medical School, Athens, Greece.
6
Division of Endocrinology, Second Department of Obstetrics and Gynecology, University of Athens Medical School, Athens, Greece.
7
Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece.

Abstract

BACKGROUND:

There have been increasing indications about an epigenetically-based elevated predisposition of assisted reproductive technology (ART) offspring to insulin resistance, which can lead to an unfavorable cardio-metabolic profile in adult life. However, the relevant long-term systematic molecular studies are limited, especially for the IntraCytoplasmic Sperm Injection (ICSI) method, introduced in 1992. In this study, we carefully defined a group of 42 prepubertal ICSI and 42 naturally conceived (NC) children. We assessed differences in their metabolic profile based on biochemical measurements, while, for a subgroup, plasma metabolomic analysis was also performed, investigating any relevant insulin resistance indices.

METHODS & RESULTS:

Auxological and biochemical parameters of 42 6.8±2.1 yrs old ICSI-conceived and 42 age-matched controls were measured. Significant differences between the groups were determined using univariate and multivariate statistics, indicating low urea and low-grade inflammation markers (YKL-40, hsCRP) and high triiodothyronine (T3) in ICSI-children compared to controls. Moreover, plasma metabolomic analysis carried out for a subgroup of 10 ICSI- and 10 NC girls using Gas Chromatography-Mass Spectrometry (GC-MS) indicated clear differences between the two groups, characterized by 36 metabolites linked to obesity, insulin resistance and metabolic syndrome. Notably, the distinction between the two girl subgroups was accentuated when both their biochemical and metabolomic measurements were employed.

CONCLUSIONS:

The present study contributes a large auxological and biochemical dataset of a well-defined group of pre-pubertal ICSI-conceived subjects to the research of the ART effect to the offspring's health. Moreover, it is the first time that the relevant usefulness of metabolomics was investigated. The acquired results are consistent with early insulin resistance in ICSI-offspring, paving the way for further systematic investigations. These data support that metabolomics may unravel metabolic differences before they become clinically or biochemically evident, underlining its utility in the ART research.

PMID:
24728198
PMCID:
PMC3984097
DOI:
10.1371/journal.pone.0094001
[Indexed for MEDLINE]
Free PMC Article

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