Lineage development in human embryos.

<p>Expression of OCT4 and GATA4 in day 5 embryos and in embryos that have been co-cultured with decidualized endometrial cells for 72 h. Scale bars are 50 µm.</p

Lineage development and H3K27me3-accumulation on the X-chromosome in human embryos.

<p>Expression of GATA4, OCT4, and H3K27me3 in human day 5 pre-implantation and embryos that have been co-cultured with decidualized endometrial cells for 72 h (day 8). Foci of H3K27me3 are diagnostic for an inactivated X-chromosome. Arrowheads denote H3K27me3 foci. The third row panels are enlargements of the indicated area in the merge panel in the above row. Scale bars are 50 µm unless denoted otherwise.</p

H3K27me3 staining of endometrial stromal cells.

<p>Accumulation of H3K27me3 on X-chromosomes was observed in >90% of the cells. Scale bars are 50 µm.</p

H3K27me3 accumulation in trophectoderm and hypoblast precursors.

<p>Expression of GATA4, and H3K27me3 in human embryos that have been co-cultured with decidualized endometrial cells for 72 h. Closed arrowheads denote GATA4 positive cells with H3K27me3 foci. Open arrowheads denote trophectoderm cells negative for OCT4 and GATA4 with distinct H3K27me3 foci. The asterisks mark cells with two H3K27me3 foci. Arrows mark the location of a diffuse H3K27me3 domain. Scale bars are 10 µm.</p

Embryo from co-culture.

<p>Human blastocyst attached to decidualized human endometrial stromal cells after 72 h of co-culture.</p

Degree of H3K27me3 foci per lineage.

<p>The percentages of cells in each lineage that carry a distinct H3K27me3 focus in embryos that have been co-cultured with decidualized endometrial cells for 72 h. Left panel: relative number of H3K27me3 per lineage as a function of the total number of cells within that lineage; middle panel: absolute values of H3K27me3 foci counted within each lineage for each embryo; right panel: relative number of H3K27me3 foci in each lineage as a function of the total number of foci observed in that embryo. H3K27me3 foci did not reveal any preferential distribution within the embryo. Green: H3K27me3 foci in OCT4 positive epiblast precursors; red: H3K27me3 foci in GATA4 positive hypoblast precursors; blue: H3K27me3 foci in OCT4- and GATA4- negative trophectoderm cells. Asterisks denote significant differences: *p<0.05. Epi = Epiblast lineage; Hypo = Hypoblast lineage; TE = Trophectoderm lineage.</p

The number of cells per lineage in human embryos.

<p>The number of cells in each lineage in embryos that have been co-cultured with decidualized endometrial cells for 72 h. Green bars are the number of OCT4 positive epiblast precursors, red bars are the number of GATA4 positive hypoblast precursors, blue bars are the number of OCT4- and GATA4- negative trophectoderm cells. Error bars denote standard deviation; asterisks denote significant differences: **: p<0.01; ***: p<0.001. Epi = Epiblast lineage; Hypo = Hypoblast lineage; TE = Trophectoderm lineage.</p

Flow chart of subject disposition during PEARL extension 2.

<p>Withdrawals are presented according to the timeframes in which they occurred, either during treatment or after treatment completion for each course.</p

Summary of laboratory parameters (Full analysis set, N = 64).

<p>Summary of laboratory parameters (Full analysis set, N = 64).</p

Summary of endometrium biopsy consensus and endometrium biopsy non-physiological descriptions (PAEC) (Full analysis set, N = 64).

<p>Summary of endometrium biopsy consensus and endometrium biopsy non-physiological descriptions (PAEC) (Full analysis set, N = 64).</p