Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure

Abstract

A key factor in the use of assisted reproductive technologies (ART) for diverse species is the safety of procedures for long-term health. By using a mouse model, we have investigated the effect of in vitro culture and embryo transfer (ET) of superovulated embryos on postnatal growth and physiological activity compared with that of embryos developing in vivo. Embryo culture from two-cell to blastocyst stages in T6 medium either with or without a protein source reduced blastocyst trophectoderm and inner cell mass cell number compared with that of embryos developing in vivo. Embryo culture and ET had minimal effects on postnatal growth when compared with in vivo development with an equivalent litter size. However, embryo culture, and to a lesser extent ET, led to an enhanced systolic blood pressure at 21 weeks compared with in vivo development independent of litter size, maternal origin, or body weight. Moreover, activity of enzymatic regulators of cardiovascular and metabolic physiology, namely, serum angiotensinconverting enzyme and the gluconeogenesis controller, hepatic phosphoenolpyruvate carboxykinase, were significantly elevated in response to embryo culture and/or ET in female offspring at 27 weeks, independent of maternal factors and postnatal growth. These animal data indicate that postnatal physiological criteria important in cardiovascular and metabolic health may be more sensitive to routine ART procedures than growth.assisted reproductive technologies ͉ in vitro culture

Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development

“…The primary mechanisms that are proposed to understand culture-induced changes in embryonic gene expression patterns include alterations in transcription and/or epigenetic reprogramming (Doherty et al 2000, Niemann & Wrenzycki 2000, Rizos et al 2003, Watkins et al 2007. We suggest that at least one additional regulatory mechanism exists that has not been largely considered to date.…”

“…There is increasing use of longer culture intervals for the production of human blastocysts in vitro (Jones & Trounson 1999) but there are concerns that assisted reproductive technologies and embryo culture are associated with increased early embryo loss, foetal growth abnormalities, disruptions in imprinting, alterations in behaviour and enhanced susceptibility to disease in later life (Sinclair et al 1999, FernandezGonzalez et al 2004, Watkins et al 2007, Owen & Segars 2009). …”

The risks of epigenetic reprogramming in children conceived by assisted reproductive technologies

“…Группа исследовате-лей под руководством А. Watkins [15] на мышиной модели изучала влияние ЭКО-ПЭ (перенос эмбрио-нов, зачатых с помощью ЭКО) и только ПЭ (перенос эмбрионов, зачатых естественным путем) на актив-ность ферментных регуляторов сердечно-сосудистой и метаболической физиологии. Они обнаружили значительно повышенный уровень обоих ферментов (ангиотензинпревращающего фермента и фосфо-энолпируват-карбоксикиназы) у потомства, зачато-го с помощью ЭКО, менее высокий, но все же повы-шенный -у потомства, зачатого in vivo, а потом пе-ренесенного другому животному с помощью ПЭ, по сравнению с животными, зачатыми естественным путем.…”

Cytoplasmic Inheritance Redux

“…There is an additional concern that IVF could result in subtle abnormalities that present later in life. For example, in mice, several studies (Calle et al, 2012;Ecker et al, 2004;FernandezGonzalez et al, 2004;Watkins et al, 2007) report long-term consequences of IVF including increased incidence of obesity, elevated systolic blood pressure and heart disease, anxiety, and memory deficits.…”