Biallelic variants in ZFP36L2 cause female infertility characterised by recurrent preimplantation embryo arrest

2021 ◽  
pp. jmedgenet-2021-107933
Author(s):  
Wei Zheng ◽  
Qian-Qian Sha ◽  
Huiling Hu ◽  
Fei Meng ◽  
Qinwei Zhou ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Preimplantation Embryo ◽  
Preimplantation Embryo Development ◽  
Maternal Mrna ◽  
Whole Exome ◽  
Genetic Abnormalities ◽  
Functional Analyses ◽  
The Relationship ◽  
Assisted Reproductive Technology Treatment

BackgroundRecurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%–30% of these cases. The underlying genetic causes for the other affected individuals remain unknown.MethodsWhole exome sequencing was performed for 100 independent infertile females that experienced RPEA. Functional characterisations of the identified candidate disease-causative variants were validated by Sanger sequencing, bioinformatics and in vitro functional analyses, and single-cell RNA sequencing of zygotes.ResultsBiallelic variants in ZFP36L2 were associated with RPEA and the recurrent variant (p.Ser308_Ser310del) prevented maternal mRNA decay in zygotes and HeLa cells.ConclusionThese findings emphasise the relevance of the relationship between maternal mRNA decay and human preimplantation embryo development and highlight a novel gene potentially responsible for RPEA, which may facilitate genetic diagnoses.

The effect of perfluorohexanesulfonate (PFHxS) on bovine preimplantation embryo development in vitro

2021 ◽  
Vol 350 ◽  
pp. S169-S170
Author(s):  
I. Hallberg ◽  
M. Moberg ◽  
M. Olovsson ◽  
P. Damdimopoulou ◽  
J. Rüegg ◽  
...  
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryo Development ◽  
Development In Vitro

Mycotoxin effects on in vitro preimplantation embryo development

1994 ◽  
Vol 11 (3) ◽  
pp. 172-175 ◽  
Author(s):  
Peter C. Svalander ◽  
Matts Olovsson ◽  
Paul V. Holmes
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryo Development

Leptin enhances porcine preimplantation embryo development in vitro

2005 ◽  
Vol 229 (1-2) ◽  
pp. 141-147 ◽  
Author(s):  
Jesse A. Craig ◽  
Hai Zhu ◽  
Paul W. Dyce ◽  
Lihua Wen ◽  
Julang Li
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryo Development ◽  
Development In Vitro

scholarly journals Mitochondria and human preimplantation embryo development

Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 619-624 ◽  
Author(s):  
Martin Wilding ◽  
Gianfranco Coppola ◽  
Brian Dale ◽  
Loredana Di Matteo
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Anaerobic Respiration ◽  
Mitochondrial Metabolism ◽  
Human Reproduction ◽  
Aerobic Respiration ◽  
Human Embryos ◽  
Developmental Potential ◽  
Preimplantation Embryo Development

Human reproduction, like all biological systems, is characterised by a large level of variability. In this field, the variability is observed as a large difference in implantation potential of human embryos developing in vitro, despite similarities in observable parameters such as rate of development and morphology of these embryos. One of the underlying factors that determines developmental potential in these embryos is the availability of energy in the form of ATP for development. Here, we suggest that, despite the evidence suggesting that mitochondrial metabolism is relatively inactive during preimplantation embryo development, aerobic (mitochondrial) metabolism contributes a major role in the supply of ATP. A second pathway, anaerobic respiration, is also active and the two pathways work in synchrony to supply all the ATP necessary. We discuss the differences in the two forms of energy production and suggest that, although anaerobic respiration can supplement deficiencies in the energy supply in the short term, this is not sufficient to substitute for aerobic respiration over long periods. Therefore, we suggest that deficiencies in the levels of aerobic respiration can explain variability in the implantation potential of apparently equivalent embryos.

scholarly journals Deadly decisions: the role of genes regulating programmed cell death in human preimplantation embryo development

Reproduction ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 281-291 ◽  
Author(s):  
Andrea Jurisicova ◽  
Beth M Acton
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Cell Fate ◽  
Embryo Development ◽  
Preimplantation Embryo ◽  
Culture Media ◽  
Culture Conditions ◽  
Early Embryo ◽  
Preimplantation Embryo Development

Human preimplantation embryo development is prone to high rates of early embryo wastage, particularly under currentin vitroculture conditions. There are many possible underlying causes for embryo demise, including DNA damage, poor embryo metabolism and the effect of suboptimal culture media, all of which could result in an imbalance in gene expression and the failed execution of basic embryonic decisions. In view of the complex interactions involved in embryo development, a thorough understanding of these parameters is essential to improving embryo quality. An increasing body of evidence indicates that cell fate (i.e. survival/differentiation or death) is determined by the outcome of specific intracellular interactions between pro- and anti-apoptotic proteins, many of which are expressed during oocyte and preimplantation embryo development. The recent availability of mutant mice lacking expression of various genes involved in the regulation of cell survival has enabled rapid progress towards identifying those molecules that are functionally important for normal oocyte and preimplantation embryo development. In this review we will discuss the current understanding of the regulation of cell death gene expression during preimplantation embryo development, with a focus on human embryology and a discussion of animal models where appropriate.

scholarly journals Intracellular oxygen metabolism during bovine oocyte and preimplantation embryo development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paul J. McKeegan ◽  
Selina F. Boardman ◽  
Amy A. Wanless ◽  
Grace Boyd ◽  
Laura J. Warwick ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxygen Consumption ◽  
Oxygen Concentration ◽  
Embryo Development ◽  
Preimplantation Embryo ◽  
Complex Iii ◽  
Preimplantation Embryos ◽  
Mitochondrial Oxygen Consumption ◽  
Preimplantation Embryo Development

AbstractWe report a novel method to profile intrcellular oxygen concentration (icO2) during in vitro mammalian oocyte and preimplantation embryo development using a commercially available multimodal phosphorescent nanosensor (MM2). Abattoir-derived bovine oocytes and embryos were incubated with MM2 in vitro. A series of inhibitors were applied during live-cell multiphoton imaging to record changes in icO2 associated with mitochondrial processes. The uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) uncouples mitochondrial oxygen consumption to its maximum, while antimycin inhibits complex III to ablate mitochondrial oxygen consumption. Increasing oxygen consumption was expected to reduce icO2 and decreasing oxygen consumption to increase icO2. Use of these inhibitors quantifies how much oxygen is consumed at basal in comparison to the upper and lower limits of mitochondrial function. icO2 measurements were compared to mitochondrial DNA copy number analysed by qPCR. Antimycin treatment increased icO2 for all stages tested, suggesting significant mitochondrial oxygen consumption at basal. icO2 of oocytes and preimplantation embryos were unaffected by FCCP treatment. Inner cell mass icO2 was lower than trophectoderm, perhaps reflecting limitations of diffusion. Mitochondrial DNA copy numbers were similar between stages in the range 0.9–4 × 106 copies and did not correlate with icO2. These results validate the MM2 probe as a sensitive, non-toxic probe of intracellular oxygen concentration in mammalian oocytes and preimplantation embryos.

257. Activation of a calcium-activated chloride channel by paf is required for normal preimplantation mouse embryo development in vitro

2008 ◽  
Vol 20 (9) ◽  
pp. 57
Author(s):  
Y. Li ◽  
M. L. Day ◽  
C. O.'Neill
Keyword(s):  
Embryo Development ◽  
Mouse Embryo ◽  
Preimplantation Embryo ◽  
Platelet Activating Factor ◽  
Outward Current ◽  
Normal Embryo ◽  
Cell Stage ◽  
Preimplantation Embryo Development ◽  
Cl Channel

Platelet activating factor (paf) is an autocrine survival factor for preimplantation embryo. Binding of paf to its receptor activates PI3kinase, causing an IP3-dependent release of Ca2+ from intracellular stores as well as activation of Ca2+ influx via a dihydropyridine-sensitive Ca2+ channel. These actions result in the generation of a defined intracellular calcium ([Ca2+]i) transient in the 2-cell embryo[1]. By using combined whole-cell patch-clamp and real-time [Ca2+]i analyses, we have shown that paf also induces a concomitant hyperpolarisation of the membrane potential in 2-cell embryos, accompanied by an increased net outward ion current. Both the membrane hyperpolarisation and outward current were dependent upon the occurrence of the paf-induced [Ca2+]i transient[2]. The aim of this study was to investigate the characteristics of the paf-induced outward current in 2-cell embryos and to assess whether it has a role in normal mouse preimplantation development. We show that: (1) removal of extracellular anions or treatment with niflumic acid (NFA, 100 μM, a Ca2+-activated Cl- channel blocker) prevented activation of the outward current by paf but had no effect on the paf-induced [Ca2+]i transient; and (2) The culture of embryos with NFA (100 μM) from the 1-cell to late 2-cell stage significantly reduced their development to the blastocyst stage (P < 0.001), but treatment with NFA from the late 2-cell stage had no effect on development. The results show that paf induces an increase in [Ca2+]i which in turn activates a Ca2+-activated Cl- channel. The activity of this NFA-sensitive channel during the zygote to 2-cell stage is required for normal embryo development. (1) C. O’Neill (2008) The potential roles of embryotrophic ligands in preimplantation embryo development. Hum Reprod Update 14:275–288. (2) Y. Li, M.L. Day & C. O’Neill (2007) Autocrine activation of ions currents in the two-cell mouse embryo. Exp Cell Res. 313:2785–2794.

Sign in / Sign up

Export Citation Format

Share Document