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In vitro fertilization and embryo culture strongly impact the placental transcriptome in the mouse model.

Fauque P, Mondon F, Letourneur F, Ripoche MA, Journot L, Barbaux S, Dandolo L, Patrat C, Wolf JP, Jouannet P, Jammes H, Vaiman D - PLoS ONE (2010)

Bottom Line: Imprinted genes were modified similarly to the X.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.

View Article: PubMed Central - PubMed

Affiliation: Service d'Histologie-Embryologie, Biologie de la Reproduction, Hôpital Cochin, Paris, France. patricia.fauque@cch.aphp.fr

ABSTRACT

Background: Assisted 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 findings: Blastocysts 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.

Conclusions: For 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.

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Histograms of gene clusters identified by DAVID for genes induced (A) and repressed (B) in IVF G1/G2.Left ordinate represents the number of genes present in each cluster and the right ordinate represents the enrichment score as defined (see text).
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pone-0009218-g004: Histograms of gene clusters identified by DAVID for genes induced (A) and repressed (B) in IVF G1/G2.Left ordinate represents the number of genes present in each cluster and the right ordinate represents the enrichment score as defined (see text).

Mentions: Seven hundred thirty eight genes (corresponding to 1,135 transcripts) induced more than two-fold in the IVF G1/G2 group, were submitted to the DAVID database to attempt a functional clustering [39], [40]. Three hundred ninety one (391) were successfully clustered into 27 functional groups, seven of which were significant according to the threshold defined (Figure 4A, see Materials and Methods). The functional classification of up-regulated genes from the IVF G1/G2 sample is summarized in Figure 4A. A large number of transcripts encoded proteins involved in growth hormone activity, cell division and mitosis, as well as DNA metabolism. These clusters suggest an increased activity of cell growth. The activated DNA metabolism may contribute to explain the massive transcriptional alterations observed on the arrays. An important category relates to protein modifications, essentially by the transcriptional activation of ubiquitin ligases.


In vitro fertilization and embryo culture strongly impact the placental transcriptome in the mouse model.

Fauque P, Mondon F, Letourneur F, Ripoche MA, Journot L, Barbaux S, Dandolo L, Patrat C, Wolf JP, Jouannet P, Jammes H, Vaiman D - PLoS ONE (2010)

Histograms of gene clusters identified by DAVID for genes induced (A) and repressed (B) in IVF G1/G2.Left ordinate represents the number of genes present in each cluster and the right ordinate represents the enrichment score as defined (see text).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2821408&req=5

pone-0009218-g004: Histograms of gene clusters identified by DAVID for genes induced (A) and repressed (B) in IVF G1/G2.Left ordinate represents the number of genes present in each cluster and the right ordinate represents the enrichment score as defined (see text).
Mentions: Seven hundred thirty eight genes (corresponding to 1,135 transcripts) induced more than two-fold in the IVF G1/G2 group, were submitted to the DAVID database to attempt a functional clustering [39], [40]. Three hundred ninety one (391) were successfully clustered into 27 functional groups, seven of which were significant according to the threshold defined (Figure 4A, see Materials and Methods). The functional classification of up-regulated genes from the IVF G1/G2 sample is summarized in Figure 4A. A large number of transcripts encoded proteins involved in growth hormone activity, cell division and mitosis, as well as DNA metabolism. These clusters suggest an increased activity of cell growth. The activated DNA metabolism may contribute to explain the massive transcriptional alterations observed on the arrays. An important category relates to protein modifications, essentially by the transcriptional activation of ubiquitin ligases.

Bottom Line: Imprinted genes were modified similarly to the X.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.

View Article: PubMed Central - PubMed

Affiliation: Service d'Histologie-Embryologie, Biologie de la Reproduction, Hôpital Cochin, Paris, France. patricia.fauque@cch.aphp.fr

ABSTRACT

Background: Assisted 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 findings: Blastocysts 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.

Conclusions: For 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.

Show MeSH