Dataset Information

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts.

ABSTRACT: Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ? 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ? 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ? 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.

SUBMITTER: Kaihola H

PROVIDER: S-EPMC6922338 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts.

Kaihola Helena H Yaldir Fatma Gülen FG Bohlin Therese T Samir Raghad R Hreinsson Julius J Åkerud Helena H

PloS one 20191219 12

Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolom ...[more]

PMID: 31856190

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Project description:PURPOSE:The aim of the study is to investigate how blastocyst contraction behaviour affects the reproductive competence in high-quality euploid embryos. METHODS:Eight hundred ninety-six high-quality blastocysts derived from 190 patients (mean age 38.05 (SD = 2.9) years) who underwent preimplantation genetic testing for aneuploidies (PGT-A) from January 2016 to October 2017 were included in this study. PGT-A results were reported as euploid or aneuploid. Aneuploid embryos were sub-classified into three categories: monosomy, trisomy and complex aneuploid. Retrospective studies of time-lapse monitoring (TLM) of those embryos were analysed and reproductive outcome of transferred embryos was collected. RESULTS:A total of 234/896 were euploid (26.1%) whilst 662/896 (73.9%) blastocysts were proven to be aneuploid from which 116 (17.6%) presented monosomies, 136 (20.5%) trisomies and 410 (61.9%) were complex aneuploid. The most frequent chromosomal complements were trisomies affecting chromosome 21 and monosomies involving chromosomes 16 and 22. Data analysis showed a statistical difference in the number of contractions being reported greater in aneuploid when compared to euploid embryos (0.6 vs 1.57; p < 0.001). Analysis of the aneuploid embryos showed that monosomies present less number of contractions when compared to embryos affected with trisomies or complex aneuploidies (1.23 vs 1.53 and 1.40; p < 0.05). No difference was observed when comparing the latter two groups. Euploid embryos presenting at least one contraction resulted in lower implantation and clinical pregnancy rates when compared to blastocysts that do not display this event (47.6 vs 78.5% and 40.0 vs 59.0% respectively). CONCLUSIONS:Most aneuploid blastocysts diagnosed by PGT-A have complex aneuploidies, showing that aneuploid embryos can develop after genomic activation and reaching high morphological scores. It becomes clear that embryo contraction, despite being a physiological feature during blastulation, is conditioned by the ploidy status of the embryo. Furthermore, the presence of contractions may compromise implantation rates.

Project description:Objective: To study post-hatching development after transfer of morphologically good quality embryos that survived in vitro maturation under lipolytic conditions using a well-established and recognized bovine model. Design: prospective study with a crossover design. Setting: research laboratory. Animals: 8 healthy multiparous non-lactating Holstein cows used in repeated embryo transfers. Intervention(s): Bovine cumulus oocyte complexes (COCs) were in vitro matured in the presence of either 1) a combination of elevated pathophysiological concentration of palmitic acid (PA) and physiological concentrations of stearic acid (SA) and oleic acid (OA) (HIGH PA), or 2) physiological concentrations of PA, SA and OA (BASAL). Matured oocytes were fertilized and cultured in FA-free conditions until day 7.7 p.i. Equal proportions of normal and expanded blastocysts were subsequently transferred to synchronized cows. Conceptuses were transcervically recovered 7 days after the transfer. Main Outcome Measure(s): Recovered embryos were morphologically assessed and dissected into embryonic disc (ED) and extraembryonic tissue (EXT). Samples of EXT were used for analysis of interferon-τ (IFN-τ) secretion and measurement of cellular metabolic activity. ED and EXT samples were subjected to RNA sequencing in order to evaluate the genome wide transcriptome patterns of recovered day 14 embryos. Results: Recovered embryos resulting from metabolically compromised oocytes were retarded in growth or less elongated than their control counterparts. Furthermore, they exhibited a decrease in glucose consumption and lactate production. Importantly, lipolytic conditions resulted in reduced capacity of the embryo to signal its presence to the mother through IFN-τ secretion. The transcriptome profile was altered in the recovered embryos with main effects in pathways related to redox-regulating mechanisms, apoptosis, cellular growth, interaction and differentiation, energy metabolism, and epigenetic mechanisms.

Dataset Information

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts.

Publications

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts.

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