Biological optimization, the Goldilocks principle, and how much islagomin the preimplantation embryo

Abstract

The quiet embryo hypothesis postulates that early embryo viability is associated with a relatively low metabolism (Leese, 2002 BioEssays 24: 845-849). This proposal is re-visited here using retrospective and prospective data on the metabolic activity and kinetics of preimplantation development alongside the concept that an optimal range of such indices and of energetic efficiency influences embryogenesis. It is concluded that these considerations may be rationalized by proposing the existence of a "Goldilocks zone," or as it is known in Sweden, of lagom-meaning "just the right amount"-within which embryos with maximum developmental potential can be categorized. Mol. Reprod. Dev. 83: 748-754, 2016 © 2016 Wiley Periodicals, Inc.

The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos

“…The ratios used in this algorithm do not favour the preferential selection of fast developing embryos, but require a synchrony in mitotic divisions. This is in line with the recent discussion that the speed of development needs to be within an optimal range, meaning that both too slow and too fast development will impact success rates [30]. The “quiet embryo hypothesis” postulates that early embryo viability is associated with a relatively stable-low metabolism [31].…”

“…The data on which this hypothesis was based were drawn from measurements on the depletion and appearance of amino acids from the culture medium. However, extending evidence on metabolic activity to the kinetics of pre-implantation embryo development, as recently reviewed by Leese and colleagues, may lead us to postulate that both too slow and too fast development result in lower success rates, due to non-optimal metabolic and/or genetic phenotype [30]. Therefore, intermediate kinetic ranges may be more physiological and may give better outcomes.…”

Listening to mother: Long‐term maternal effects in mammalian development

“…A key point to bear in mind regarding mitochondrial activity in the oocyte is that the precise level of mitochondrial activity appears to be critical (Leese et al, 2016). Mitochondrial insufficiency is highly detrimental to short‐term embryonic phenotype (Al‐Zubaidi et al, 2019), but, conversely too much mitochondrial activity can be detrimental, as it can be associated with excess production of ROS (Leese et al, 2016).…”

“…A key point to bear in mind regarding mitochondrial activity in the oocyte is that the precise level of mitochondrial activity appears to be critical (Leese et al, 2016). Mitochondrial insufficiency is highly detrimental to short‐term embryonic phenotype (Al‐Zubaidi et al, 2019), but, conversely too much mitochondrial activity can be detrimental, as it can be associated with excess production of ROS (Leese et al, 2016). The production of excess ROS is especially problematic for oocytes and zygotes because, compared to somatic cells, they are deficient in some of the enzymes that are needed to eliminate ROS, acquiring these ROS scavenging molecules instead from the follicular or oviductal fluid (Guerin, El Mouatassim, & Menezo, 2001; Ufer & Wang, 2011).…”

Professor Henry J Leese: honorary member of the European Society of Human Reproduction and Embryology

“…Instead of considering only noisy and quiet embryos, we now look at the whole distribution of activity. Rather than just being two categories, embryo metabolism appears to obey the Goldilocks or 'lagom' principle, whereby 'just enough' metabolism is sufficient (Leese et al, 2016).…”