In Vitro Fertilization and Embryo Culture Strongly Impact the Placental Transcriptome in the Mouse Model

Abstract

BackgroundAssisted Reproductive Technologies (ART) are increasingly used in humans; however, their impact is now questioned. At blastocyst stage, the trophectoderm is directly in contact with an artificial medium environment, which can impact placental development. This study was designed to carry out an in-depth analysis of the placental transcriptome after ART in mice.Methodology/Principal FindingsBlastocysts were transferred either (1) after in vivo fertilization and development (control group) or (2) after in vitro fertilization and embryo culture. Placentas were then analyzed at E10.5. Six percent of transcripts were altered at the two-fold threshold in placentas of manipulated embryos, 2/3 of transcripts being down-regulated. Strikingly, the X-chromosome harbors 11% of altered genes, 2/3 being induced. Imprinted genes were modified similarly to the X. Promoter composition analysis indicates that FOXA transcription factors may be involved in the transcriptional deregulations.ConclusionsFor the first time, our study shows that in vitro fertilization associated with embryo culture strongly modify the placental expression profile, long after embryo manipulations, meaning that the stress of artificial environment is memorized after implantation. Expression of X and imprinted genes is also greatly modulated probably to adapt to adverse conditions. Our results highlight the importance of studying human placentas from ART.

Stress-Induced Enzyme Activation Primes Murine Embryonic Stem Cells to Differentiate Toward the First Extraembryonic Lineage

“…T ranscription factor (TF) expression and therefore lineage identity in the peri-implantation embryo and its stem cells may be influenced by extracellular stresses [1,2]. Perturbations of the embryo during the critical period of implantation frequently lead to loss of the pregnancy [3,4].…”

Angiogenic markers in pregnancies conceived through in vitro fertilization

“…Increasing data are establishing IVF placentas to be morphologically different; in a murine model, placentas in the IVF-exposed group were shown to have impaired amino acid and nutrient transport mechanisms. 11 IVF placentas have also been shown to have altered glucocorticoid metabolism 12 and expression of placenta genes 13,14 when compared with spontaneous conceptions, which further suggests that abnormal placentation partly may explain the difference in observed pregnancy outcomes.…”

Embryo formation from low sperm concentration by using dielectrophoretic force

“…In the future, we shall continue to test the limit of sperm concentration that is still able to achieve mouse fertilization in vitro, to integrate the embryo culture in vitro into our biochip and then to transplant embryo into the uterus of the ICR mice. Our goal is to develop a concept of a labon-chip 11,14,[19][20][21][22] for assisted reproduction techniques in vitro.…”