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Christopher Price and Greg FitzHarris
Cayetana Vázquez-Diez and Greg FitzHarris
Errors in chromosome segregation are common during the mitotic divisions of preimplantation development in mammalian embryos, giving rise to so-called ‘mosaic’ embryos possessing a mixture of euploid and aneuploid cells. Mosaicism is widely considered to be detrimental to embryo quality and is frequently used as criteria to select embryos for transfer in human fertility clinics. However, despite the clear clinical importance, the underlying defects in cell division that result in mosaic aneuploidy remain elusive. In this review, we summarise recent findings from clinical and animal model studies that provide new insights into the fundamental mechanisms of chromosome segregation in the highly unusual cellular environment of early preimplantation development and consider recent clues as to why errors should commonly occur in this setting. We furthermore discuss recent evidence suggesting that mosaicism is not an irrevocable barrier to a healthy pregnancy. Understanding the causes and biological impacts of mosaic aneuploidy will be pivotal in the development and fine-tuning of clinical embryo selection methods.
Greg FitzHarris and Jay M Baltz
Regulation of intracellular pH (pHi) is a fundamental homeostatic process essential for the survival and proliferation of virtually all cell types. The mammalian preimplantation embryo, for example, possesses Na+/H+ and HCO3 −/Cl− exchangers that robustly regulate against acidosis and alkalosis respectively. Inhibition of these transporters prevents pH corrections and, perhaps unsurprisingly, leads to impaired embryogenesis. However, recent studies have revealed that the role and regulation of pHi is somewhat more complex in the case of the developing and maturing oocyte. Small meiotically incompetent growing oocytes are apparently incapable of regulating their own pHi, and instead rely upon the surrounding granulosa cells to correct ooplasmic pH, until such a time that the oocyte has developed the capacity to regulate its own pHi. Later, during meiotic maturation, pHi-regulating activities that were developed during growth are inactivated, apparently under the control of MAPK signalling, until the oocyte is successfully fertilized. Here, we will discuss pH homeostasis in early mammalian development, focussing on recent developments highlighting the unusual and unexpected scenario of pH regulation during oocyte growth and maturation.
Greg FitzHarris and Christopher Price
Lia Mara Gomes Paim and Greg FitzHarris
Preimplantation embryos frequently contain binucleated cells, but reports differ as to whether binucleation affects development and whether such embryos should be used clinically. In this Point Of View article, we propose a possible explanation for this disparity: binucleation can arise by distinct routes, one that produces healthy blastomeres and one that directly threatens embryo viability.