Rocking the human embryo – pari passu
Article Outline
The human embryo in vivo is exposed to biochemically and biophysically dynamic conditions when it traverses the Fallopian tube. Artificial culture systems appear static in comparison, although this relative calm is interrupted periodically by hand-carrying dishes to and from the microscope concurrent with culture media changeovers. Experimental embryologists have been aware of this presumed discrepancy between in-vitro and in-vivo culture and as far back as the 1970s developed various devices to generate continuous movement around embryos; this was to replicate natural conditions. Gerard Zeilmaker of Erasmus University in Rotterdam in The Netherlands applied a gently shaking heated platform placed in a room warmed to 37°C (Zeilmaker, 1973). The same system was used in a study involving the in-vitro effects of dihydrotestosterone inhibition on mouse embryo development (Cohen et al., 1981). Relatively small droplets of culture medium were placed under paraffin oil in individually gassed Petri dishes with the help of an ingeniously placed tubing system bubbling gas into each dish individually. The system was calibrated to reduce oil spillage and promote embryo development. The humidified gas phase had 5% O2, 5% CO2 and 90% N2 and the movement was circular in the horizontal plane. Neither reduced oxygen tension nor dynamic culture systems were investigated in depth until clinical embryologists set out to methodically optimize embryo culture systems many years later (Gardner and Lane, 1997, Meintjes et al., 2009, Suh et al., 2003, Xie et al., 2007). Dynamic culture systems, particularly microfluidics, have led the way to study physical phenomena such as shear stress and kinetic friction. In this re-emerging area of interest, there is considerable room for investigation, particularly since it is unclear what physical conditions are conducive to better embryo development or whether there are species differences and specific levels of tolerance. Accurately describing and testing artificial dynamic systems in preclinical studies is therefore both necessary and useful. There are two very recent papers that are worth mentioning in this context. In January, the pioneering group of Gary Smith in Ann Arbor presented an elegant comparative study describing a dynamic microfunnel system (Heo et al., in press). In this issue of Reproductive BioMedicine Online, a multicenter investigation from Japan by Matsuura and co-workers presents the application of a tilting embryo culture system called TECS placed inside an incubator and its effect on mouse and human embryos (Matsuura et al., 2010). The two studies are similar in that they both show modestly positive effects on embryo development to the blastocyst stage. Whereas microfluidics may have advantages related to controlled biochemical changes, movement, shear stress, flow, compression and other factors, it is challenging to pinpoint the cause(s) of its development-enhancing effects. The experiments by the Japanese team using TECS were conducted in larger volumes than those utilized in the microfluidics system. The positive effects of TECS must be mechanical in nature, begging the question whether the microfluidic system operates in a similar way?
TECS leads the way to developing relatively uncomplicated devices inside or underneath incubators, which can control movement – devices that could be applied without much change to existing culture systems. Amplitude, angle, frequency and speed of motion will need to be assessed as elegantly addressed by the Japanese investigators. Devices placed inside incubators will need to be evaluated carefully for potential release of volatile organic compounds, background vibration and electromagnetic radiation. Waterproofing alone, as suggested by the investigators, is a good start to control leakage, durability and optimal performance. The first prospective clinical study using TECS is now underway in IVF clinics in Japan.
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PII: S1472-6483(10)00055-6
doi:10.1016/j.rbmo.2010.02.001
© 2010 Published by Elsevier Inc.
