Impact of embryo culture and day of embryo transfer on the cardiometabolic health of adult mice

Assisted reproductive technologies (ARTs) have rapidly evolved since being introduced in 1978. However, many of the procedures used clinically lack a basis of long-term studies to ensure their safety. Though in vitro fertilization (IVF) is largely safe, follow-up studies have shown that IVF-conceived children may show signs of altered fat deposition, increased fasting glucose, and increased blood pressure. These results are, however, limited by a low number of patients and different ART variables (different lengths of embryo culture or different types of culture media). Results of studies using animal models have confirmed many of these results and shown that more stressful culture conditions result in disrupted adult phenotypes. Presently, it is unclear if culture conditions such as duration and day of transfer might affect adult health. To investigate the hypothesis that the length of embryo culture could affect adult phenotype, we generated mice by IVF and transferred them at the cleavage stage (IVF8C group) or at the blastocyst stage (IVFBL group) and studied adult phenotype. Results were compared to those obtained with naturally conceived animals flushed out of the uterus and transferred to the recipient (FB group). We found sexual dimorphic effects with male mice showing a more severe phenotype. Male offspring resulting from cleavage stage transfer showed altered glucose handling, left cardiac dysfunction, and shorter lifespan, while male offspring post blastocyst transfer showed reduced locomotor activity. Female mice showed a milder phenotype, particular for female offspring generated by transfer at the cleavage stage.