Grade and looseness of the inner cell mass may lead to the development of monochorionic diamniotic twins

Otsuki, Junko; Iwasaki, Tadaaki; Katada, Yuya; Sato, Haruka; Furuhashi, Kohyu; Tsuji, Yuta; Matsumoto, Yukiko; Shiotani, Masahide

doi:10.1016/j.fertnstert.2016.05.007

Cited by 30 publications

(19 citation statements)

References 20 publications

(20 reference statements)

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“…These results indicate that α-KG is an important metabolite that promotes embryonic development because α-KG reduces embryo ATP production and activates the TET enzyme, thereby enhancing the ICM and the competence of the blastocyst. The findings were consistent with previous observations that the ICM grade is positively related to birth weight (Licciardi et al 2015) and the survival rate of transplanted embryos (Otsuki et al 2016, Subira et al 2016). In humans, blastocysts with larger ICMs are more likely to implant after transfer than those with smaller ICMs (Richter et al 2001).…”

Section: Discussionsupporting

confidence: 92%

Alpha-ketoglutarate affects murine embryo development through metabolic and epigenetic modulations

Zhang

et al. 2019

Reproduction

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α-Ketoglutarate (α-KG) is an intermediary metabolite in the tricarboxylic acid (TCA) cycle and functions to inhibit ATPase and maintain the pluripotency of embryonic stem cells (ESCs); however, little is known regarding the effects of α-KG on the development of preimplantation embryos. Herein, we report that α-KG (150 μM) treatment significantly promoted the blastocyst rate, the number of inner cell mass (ICM) cells and foetal growth after embryo transfer. Mechanistic studies revealed two important pathways involved in the α-KG effects on embryo development. First, α-KG modulates mitochondria function by inducing relatively low ATP production without modification of mitochondrial copy number. The relatively low energy metabolism preserves the pluripotency and competence of the ICM. Second, α-KG modifies epigenetics in embryos cultured in vitro by affecting the activity of the DNA demethylation enzyme TET and the DNA methylation gene Dnmt3a to increase the ratio of 5hmC/5mC ratio. Elevation of the 5hmC/5mC ratio not only promotes the pluripotency of the ICM but also leads to a methylation level in an in vitro embryo close to that in an in vivo embryo. All these functions of α-KG collectively contribute to an increase in the number of ICM cells, leading to greater adaptation of cultured embryos to in vitro conditions and promoting foetal growth after embryo transfer. Our findings provide basic knowledge regarding the mechanisms by which α-KG affects embryo development and cell differentiation.

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Section: Discussionsupporting

confidence: 92%

Alpha-ketoglutarate affects murine embryo development through metabolic and epigenetic modulations

Zhang

et al. 2019

Reproduction

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“…This sometimes occurs during frozen‐thawed embryo transfer cycles with hormone therapy and such conceptions cannot be eliminated in this study, although the incidence is very small 10, 16. Also, the analysis of the pronuclear size is restricted to 2‐D measurements in this study.…”

Section: Discussionmentioning

confidence: 99%

“…This sometimes occurs during frozen-thawed embryo transfer cycles with hormone therapy and such conceptions cannot be eliminated in this study, although the incidence is very small. 10,16 Also, the analysis of the pronuclear size is restricted to 2-D measurements in this study. It is possible that more precise data could be obtained In this study, the authors focused on successful live birth rates, rather than blastocyst development and pregnancy rates, as >50% of blastocysts are known to have abnormal chromosomal configurations and most of those embryos result in a miscarriage.…”

Section: Discussionmentioning

confidence: 99%

Potential of zygotes to produce live births can be identified by the size of the male and female pronuclei just before their membranes break down

Otsuki

Iwasaki

Tsuji

et al. 2017

Reprod Medicine & Biology

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AimTo determine whether there are differences in size between the male and female pronuclei immediately before the pronuclear membrane breakdown (PNMBD) and to evaluate whether pronuclear size differences influence normal birth rates.MethodsTime‐lapse photography was used to measure the size of each pronucleus, while the outcome of 71 frozen‐thawed single blastocyst transfers in patients receiving hormone therapy was analyzed retrospectively. The pronuclear measurements were made 4 hours before the PNMBD, corresponding to 16‐20 hours after insemination or intracytoplasmic sperm injection, and immediately before the PNMBD. The differences in the areas between the pronuclei in the zygotes that were associated with the live births were compared with those that were associated with the failed pregnancies.ResultsThe average difference in the area between the pronuclei 4 hours before and immediately before the PNMBD in the patients with a live birth was significantly smaller than in the patients with a failed birth. In addition, the average area difference in the patients with a successful birth was significantly smaller when the measurements were made immediately before the PNMBD, compared with the measurements 4 hours before the PNMBD. Such differences were not detected among the patients who did not achieve a birth.ConclusionThe birth of healthy babies resulted from zygotes that contained pronuclei of similar size when the measurements were made immediately before the PNMBD. Evaluating the size of each pronucleus immediately before the PNMBD provides an effective indicator of the embryo's potential at an early stage of development.

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“…Previous work has indicated that the ICM grade or cell-adhesion looseness is related to MZT development [13], and in mouse, a delay in inter-cell adhesion has been shown to increase ICM division [14]. Because the scattered ICM arising from “8”-shaped hatching is considered to represent a state of cell-adhesion looseness, the occurrence of “8”-shaped hatching near the ICM could potentially be the factor that elicits MZT.…”

Section: Discussionmentioning

confidence: 99%

The location of “8”-shaped hatching influences inner cell mass formation in mouse blastocysts

et al. 2017

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The hatching of a blastocyst where the blastocyst portions on the inside and the outside of the zona pellucida feature a figure-of-eight shape is termed “8”-shaped hatching; this type of hatching has been reported to affect the proper presentation of the inner cell mass (ICM) in both human and mouse embryos. Here, our aim was to investigate the factors that affect ICM presentation during “8”-shaped hatching. We performed IVF by using B6D2F1 female mice and ICR male mice, and used the 104 captured blastocysts. Embryos were maintained in KSOM at 37°C in a 5% CO2, 5% O2, and 90% N2 environment, and their growth behavior was monitored individually and continuously using time-lapse cinematography. At 120 h after insemination, embryos were immunostained and examined under a confocal microscope. We used the hatching form to identify “8”-shaped hatching, and we classified the “8”-shaped-hatching blastocysts into two groups, one in which the hatching site was near the ICM center, and the other in which the hatching site was far from the ICM center. We measured each group for ICM size and the number of Oct3/4-positive cells. Of the 95 hatching or hatched embryos, 74 were “8”-shaped-hatching blastocysts, and in these embryos, the ICM was significantly wider when the hatching site was near the ICM than when the hatching site was far from the ICM (P = 0.0091). Moreover, in the “8”-shaped-hatching blastocysts in which the ICM was included in the blastocyst portion outside the zona pellucida―the portion defined as the “outside blastocyst”―after the collapse of this outside blastocyst, the ICM adhered to the trophectoderm of the outside blastocyst, opposite the hatching site. Our results indicate that in “8”-shaped-hatching blastocysts, the hatching site and the collapse of outside blastocyst affect ICM formation. Thus, the assessment of “8”-shaped hatching behaviors could yield indices for accurately evaluating embryo quality.

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Grade and looseness of the inner cell mass may lead to the development of monochorionic diamniotic twins

Abstract: The occurrence of M-D twinning may be avoided by excluding blastocysts that contain decompacting ICMs.

Cited by 30 publications

References 20 publications

Alpha-ketoglutarate affects murine embryo development through metabolic and epigenetic modulations

Alpha-ketoglutarate affects murine embryo development through metabolic and epigenetic modulations

Potential of zygotes to produce live births can be identified by the size of the male and female pronuclei just before their membranes break down

The location of “8”-shaped hatching influences inner cell mass formation in mouse blastocysts

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