Differential pH in embryo culture

Hentemann, Martha; Mousavi, Karim; Bertheussen, Kjell

doi:10.1016/j.fertnstert.2010.10.018

Cited by 33 publications

(17 citation statements)

References 15 publications

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“…Inadequate culture conditions do not allow the embryo to preserve its homeostasis, resulting in short-term alterations in morphology, cell proliferation, apoptosis and metabolism. Over the longer term, adverse effects include reduced pregnancy rate, increased abortion risk, congenital abnormalities, postnatal death and diseases in adulthood (Hentemann et al 2011). …”

Section: Discussionmentioning

confidence: 99%

Effect of mesenchymal stem cells and mouse embryonic fibroblasts on the development of preimplantation mouse embryos

Jasmin

Peters

Spray

et al. 2016

In Vitro Cell.Dev.Biol.-Animal

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Summary Despite advances in assisted reproduction techniques, the poor quality and failures in embryo in vitro development remain as drawbacks resulting in low pregnancy rate. Mouse embryonic fibroblasts (MEFs) have been widely used to support embryonic stem cells. Mesenchymal cells (MSCs) have also been shown to release bioactive factors. In the present study we have evaluated the ability of MSCs and MEFs to support early development of mouse embryos. The embryos were cultivated alone or in coculture with inactivated MSC or MEF for 4 days. After 4 days in culture the percentage of blastocyst formation in coculture with MSC (91.7±4.3%) or MEF (95.1±3.3%) was higher than in the control group (72.2±9.0%). We did not observe any difference in proliferation or apoptosis. However, the blastocysts cocultured with MSC or MEF presented a significantly higher number of cells within the inner cell mass per embryo when compared to controls. The MSC and MEF groups presented also a higher cell number and diameter when compared to the CTRL. In summary, our data indicate that coculture with MSC or MEF improve early embryonic development and quality in vitro.

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Section: Discussionmentioning

confidence: 99%

Effect of mesenchymal stem cells and mouse embryonic fibroblasts on the development of preimplantation mouse embryos

Jasmin

Peters

Spray

et al. 2016

In Vitro Cell.Dev.Biol.-Animal

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“…In the mammalian reproductive tract, gametes and cleavage stage embryos are exposed to markedly alkaline conditions in the oviduct (pH ≥7.5), before implanting into a more acidic uterine environment (pH 6.96) (Zhao and Baltz, ). The stratified reproductive environment is suggestive of stage‐specific pH requirements during fertilization and preimplantation development, a theory validated by a recent study demonstrating enhanced development of cultured embryos allowed to progress through cleavage stages at higher pH before transition into a more acidic pH after compaction (Hentemann et al, ).…”

Section: Potential Sources Of In Vitro Stress Occurring During the Prmentioning

confidence: 90%

Preimplantation Stress and Development

Feuer

Rinaudo

2012

Birth Defects Research Pt C

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The developmental origins of health and disease hypothesis holds that inappropriate environmental cues in utero, a period marked by tremendous developmental sensitivity, facilitate cellular reprogramming to ultimately predispose disease in adulthood. In this review, we analyze if stress during early stages of development can affect future health. This has wide clinical importance, given that 5 million children have been conceived with assisted reproductive technologies (ART). Because the primary outcome of assisted reproduction procedures is delivery at term of a live, healthy baby, the postnatal effects occurring outside of the neonatal period are often overlooked. To this end, the long-term outcome of ART is appropriately the most relevant concern of the field today. Evidence of adverse consequences is controversial. The majority of studies have concluded no obvious problems in IVF-conceived children, although a number of isolated cases of imprinted diseases, cancers, or malformations have been reported. Given that animal studies suggest alteration of metabolic pathways following preimplantation stress, it will be of great importance to follow-up ART individuals as they enter later stages of adult life.

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“…Our in vitro study points to an interesting hypothesis that lactic acid may work together with other signaling pathways to maintain the self-renewal and pluripotency of epiblast cells during early embryonic stages. Consistent with this, embryos passing 8-cell stage, approximately when the metabolism of an embryo shifts to glycolysis, prefers culture media with lower pH for full development 42 . In addition, Ldha knockout leads to preimplantation death in mouse embryos (The Sanger Mouse Genetics Program).…”

Section: Discussionmentioning

confidence: 52%

Acidic microenvironment shaped by lactate accumulation promotes pluripotency through multiple mechanisms

Wang

Zhang

et al. 2018

Preprint

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Enhanced glycolysis is a distinct feature associated with numerous stem cells and cancer cells. However, little is known about its regulatory roles in gene expression and cell fate determination. Here we show that acidic environment shaped by lactate accumulation promotes the self-renewal and pluripotency of both mouse and human embryonic stem cells (ESCs). Mechanistically, acidic pH reduces the tri-methylation of H3K27 globally at transcriptional start sites to partially prevent ESC differentiation. In addition, acidic pH stabilizes a large number of mRNAs including pluripotency genes. Furthermore, we found that AGO1 protein is downregulated at acidic conditions, leading to the de-repression of a subset of microRNA targets in low-pH treated ESCs. Altogether, our study provides insights into mechanisms whereby acidic microenvironment produced by enhanced glycolysis regulates gene expression to determine cell fate and has broad implications in the fields of regenerative medicine and cancer biology.

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Differential pH in embryo culture

Cited by 33 publications

References 15 publications

Effect of mesenchymal stem cells and mouse embryonic fibroblasts on the development of preimplantation mouse embryos

Effect of mesenchymal stem cells and mouse embryonic fibroblasts on the development of preimplantation mouse embryos

Preimplantation Stress and Development

Acidic microenvironment shaped by lactate accumulation promotes pluripotency through multiple mechanisms

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