The metabolism of pre-implantation embryos is far from being understood. In human embryos, the two major obstacles are the scarcity of material, for obvious ethical reasons, and complete absence of a relevant in vivo control model. Over-extrapolation from animal species to human systems adds to the complexity of the problem. Removal of some metabolites from media has been proposed, such as glucose and essential amino acids, on the basis of their pseudo "toxicity". In contrast, addition of some compounds such as growth factors has been proposed in order to decrease apoptosis, which is a natural physiologic process. These suggestions reflect the absence of global knowledge, and in consequence mask reality. Some aspects of metabolism have been ignored, such as lipid metabolism. Others are seriously underestimated, such as oxidative stress and its relationship to imprinting/methylation, of paramount importance for genetic regulation and chromosomal stability. It has become increasingly obvious that more studies are essential, especially in view of the major extension of ART activities worldwide.
Purpose The purpose of this study is to study lipid metabolism in oocytes and embryos that is a neglected parameter in human IVF. Methods We have tested the total carnitine content (TC) in the follicular fluid of 278 patients (217 non pregnant, 61 pregnant) undergoing IVF. Results The follicular fluid TC is neither correlated with the circulating estradiol content in serum nor with the outcome the IVF attempt. Carnitine, through the carnitine shuttle, is a major partner in lipid beta oxidation, metabolic pathway involved in the acquisition of oocyte competence. The expression of carnitine synthesis enzymes and lipid beta oxidation was studied in cumulus cells collected at the time of ovum retrieval and in oocyte. Surprisingly the expression for carnitine synthesis is not detectable in oocytes whereas the enzymes involved in lipid beta oxidation are rather strongly expressed. Conclusions The addition of carnitine in oocyte maturation and embryo culture media should not be overlooked.
One of the most important concerns in assisted reproduction (ART), and in particular ICSI, is the quality of sperm DNA. Oxidative stress is one of the major causes of damage to DNA and attempting to reduce generation of DNA damage related to reactive oxygen species (ROS) through consumption of antioxidants is often tempting. However, current antioxidant treatments, given irrespectively of clinically quantified deficiencies, are poorly efficient, potentially detrimental and over-exposure is risky. Here we discuss new treatments in relation to present day concepts on oxidative stress. This discussion includes stimulation of endogenous anti-ROS defense i.e. glutathione synthesis and recycling of homocysteine, the epicentre of multiple ROS-linked pathologies.
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