Abstract

Elevated non-esterified fatty acid (NEFA), predominantly palmitic acid (PA), concentrations in blood and follicular fluid are a common feature in maternal metabolic disorders such as obesity. This has a direct negative impact on oocyte developmental competence and the resulting blastocyst quality. We use NEFA-exposure during bovine oocyte in vitro maturation (IVM) as a model to mimic oocyte maturation under maternal metabolic stress conditions. However, the impact of supportive embryo culture conditions on these metabolically compromised zygotes are not known yet. We investigated if the addition of anti-apoptotic, antioxidative and mitogenic factors (namely, Insulin-Transferrin-Selenium (ITS) or serum) to embryo culture media would rescue development and important embryo quality parameters (cell proliferation, apoptosis, cellular metabolism and gene expression patterns) of bovine embryos derived from high PA- or high NEFA-exposed oocytes when compared to controls (exposed to basal NEFA concentrations). ITS supplementation during in vitro culture of PA-exposed oocytes supported the development of lower quality embryos during earlier development. However, surviving blastocysts were of inferior quality. In contrast, addition of serum to the culture medium did not improve developmental competence of PA-exposed oocytes. Furthermore, surviving embryos displayed higher apoptotic cell indices and an aberrant cellular metabolism. We conclude that some supportive embryo culture supplements like ITS and serum may increase IVF success rates of metabolically compromised oocytes but this may increase the risk of reduced embryo quality and may thus have other long-term consequences.

Highlights

  • Maternal metabolic disorders like obesity are known to affect reproductive physiology, leading to a disappointing fertility

  • We investigated the effects on developmental competence as well as on important embryo quality parameters: cell proliferation, apoptosis, embryonic cell metabolism and expression of a selected number of genes related to oxidative stress, mitochondrial unfolded protein response, endoplasmic reticulum stress and mitochondrial biogenesis

  • We confirmed that high non-esterified fatty acid (NEFA) exposure during in vitro oocyte maturation (IVM) significantly reduced embryo developmental competence when cultured in basic SOF medium

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Summary

Introduction

Maternal metabolic disorders like obesity are known to affect reproductive physiology, leading to a disappointing fertility. Incidences of these metabolic health disorders are dramatically increasing worldwide and have been strongly linked to a significant loss of reproductive capacity [1,2]. It has been shown that elevated NEFA concentrations in the FF directly affects oocyte developmental capacity [4], and has been associated with poor cumulus-oocyte-complex morphology in humans [7]. When FF of obese patients was added during bovine in vitro oocyte maturation (IVM), oocyte developmental competence and embryo quality were negatively affected [9]. Exposure to a mixture of predominant NEFAs (PA, SA and OA) or to PA only at pathophysiological concentrations during IVM increased apoptosis in cumulus cells [4], altered expression of genes related to oxidative stress in oocytes, reduced embryo development to the blastocyst stage, reduced blastocyst cell numbers and increased blastocyst apoptotic cell indices compared to NEFA-free controls [13,14,15,16]

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