Understanding the impact of ovarian stimulation on oocyte and embryo quality by tandem RNA and protein expression analysis of oocytes and preimplantation embryonic stages
Final Report Abstract
Using the paradigm of gonadotropin-induced superovulation, co-PIs Leila Taher, Georg Fuellen and Michele Boiani applied mass spectrometry, RNA sequencing and bioinformatic analysis to study the impact on oocyte and embryo quality of a common treatment used in medically- assisted reproduction, in the mouse model of human reproduction. Our published and submitted work showed that 1), in the vast majority of cases, transcript profiles offer no reliable information about protein profiles; 2) protein abundances can be expressed using the riBAQ algorithm, which returns values in the vicinity of picomoles, thereby enabling an educated and accurate targeting of gene product for destruction directly at the protein level (e.g. ‘Trim- away’); 3) the superovulation changes the abundance of specific proteins in oocytes and embryos, without any significant change in the transcriptome. The third and last finding was the most surprising, because it could not have been predicted otherwise. Who knows how many other false negatives there are to be uncovered in the field of the treatments used in medically- assisted reproduction (i.e. treatments regarded to as free of side effects according to transcript analysis, while in fact those effects are there, just in another stage of the gene expression cascade). Together, these findings make us aware that a potential threat for oocyte quality has been underestimated when the sole transcriptome is examined, and that superovulated oocytes are clearly distinguishable from – and probably inferior to - naturally ovulated oocytes, in terms of protein composition. Thus, conclusions about oocyte quality in the context of ovarian stimulation (human) and superovulation (mice) might be not as safe as we had assumed, and derivative embryos might not support conclusions that universally apply for natural development. The progress reported here would not have been possible without the development of suitable bioinformatic pipelines, delivered by co-PIs Leila Taher and Georg Fuellen, which disentangled the complexity of the biological data of co-PI Michele Boiani.
Publications
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The proteome, not the transcriptome, predicts that oocyte superovulation affects embryonic phenotypes in mice
Taher L, Israel S, Drexler HCA, Makalowski W, Suzuki Y, Fuellen G, Boiani M
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Unexpected protein dynamics during the oocyte-to-embryo transition in mice: a mass spectrometry and RNA sequencing tandem study. Reproduction, Fertility and Development 30:172-172, 2017
Israel S, Ernst M, Psathaki OE, Drexler HC, Casser E, Suzuki Y, Makalowski W, Fuellen G, Boiani M, Taher L
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A framework for TRIM21-mediated protein depletion in early mouse embryos: recapitulation of Tead4 null phenotype over three days. BMC Genomics 20(1):755, 2019
Israel S, Casser E, Drexler HCA, Fuellen G, Boiani M
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An integrated genome-wide multi-omics analysis of gene expression dynamics in the preimplantation mouse embryo. Scientific Reports 9(1):13356, 2019
Israel S, Ernst M, Psathaki OE, Drexler HCA, Casser E, Suzuki Y, Makalowski W, Boiani M, Fuellen G, Taher L
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Totipotency continuity from zygote to early blastomeres: a model under revision. Reproduction 158(2):R49-R65, 2019
Boiani M, Casser E, Fuellen G, Christians ES
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Conventional ovarian stimulation with gonadotropins depletes the developmental proteome of mouse oocytes, reducing their size and compromising their fetal yield. Human Reproduction 36:84-85, 2021 Supplement 1 Meeting Abstract O-169
Boiani M, Drexler HC, Fuellen G, Israel S, Makalowski W, Suzuki Y, Taher L
