Obstet Gynecol Sci.  2023 Sep;66(5):417-429. 10.5468/ogs.22315.

Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer

• Choo SP
• Lee I
• Lee JH
• Lee D
• Park H
• Park JH
• Cho S
• Choi YS

• KMID: 2545888
• DOI: http://doi.org/10.5468/ogs.22315

Abstract

Objective
This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET).
Methods
Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups.
Results
Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group.
Conclusion
Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Keyword

Endometrium; Luteal phase; Transcriptome; Embryo implantation

Figure

• 

  Fig. 1 Heatmaps of normalized gene expression data generated by the NanoString nSolver software via unsupervised clustering in the (A) pregnant group and (B) non-pregnant group. The heatmaps are scaled to give all genes equal variance. Within the gene clusters, red indicates high expression and green indicates low expression. The red rectangles indicate genes differentially expressed in the mid-secretory phase endometrium, compared with the early secretory phase endometrium, within each patient group. PLK2, polo like kinase 2; GPD1L, glycerol-3-phosphate dehydrogenase 1 like; FCGR3B, Fc gamma receptor IIIb; SERPINE1, serpin family E member 1; GLB1L2, galactosidase beta 1 like 2; ADRA2A, adrenoceptor alpha 2A; TMEM252, transmembrane protein 252; ITGA2, integrin subunit alpha 2; HAP1, huntingtin associated protein 1; LAMA2, laminin sub¬unit alpha 2; SMAD7, SMAD family member 7; MASP1, MBL associated serine protease 1; SPTLC3, serine palmitoyltransferase long chain base subunit 3; CILP, cartilage intermediate layer protein; C200f27, chromosome 20 open reading frame 27; ADAMTS8, a disintegrin and metalloproteinase with thrombospondin type 1 motifs, 8; SLC2A8, solute carrier family 2 member 8; APCDD1, adenomatosis polyposis coli down-regulated 1; TMEM37, transmembrane protein 37; ADAMTS15, a disintegrin and metal¬loproteinase with thrombospondin type 1 motifs, 15; 2CD4A, C2 calcium dependent domain containing 4A; MAOA, monoamine oxidase A; VNN3, vanin 3; KCNJ15, potassium inwardly rectifying channel subfamily J member 15; TNS4, tensin 4; TGM5, transglutaminase 5; FCAR, Fc fragment of IgA receptor; CEACAM3, carcinoembryonic antigen-related cell adhesion molecule 3; TFAP2A, transcription factor AP-2 alpha; ITGB3, integrin subunit beta 3; RND3, Rho family GTPase 3; CYP24A1, cytochrome P450 family 24 subfamily A member 1; IRAK2, interleukin 1 receptor associated kinase 2; NRG1, neuregulin 1; FPR1, formyl peptide receptor 1; SELL, selectin L; IL7R, interleukin 7 receptor; MMP25, matrix metallopeptidase 25; CCRL2, C-C motif chemokine receptor like 2; ADGRE3, adhesion G protein-coupled receptor E3; TSC22D1, transforming growth factor-beta-stimulated clone 22 domain family member 1; NRIP3, nuclear receptor interacting protein 3; OLR1, oxidized low density lipoprotein receptor 1; SLC11A1, solute carrier family 11 member 1; C2CD4A, C2 calcium dependent domain containing 4A; GPDIL, glycerol-3-phosphate dehydrogenase 1 like; ITGB6, integrin subunit beta 6.

• 

  Fig. 2 Volcano plots of genes differentially expressed between the early secretory phase and mid-secretory phase endometrium in the (A) pregnant group and (B) non-pregnant group. Log2 fold-change differences between the early and mid-secretory endometria are shown on the X-axis, and negative log of P-values are shown on the Y-axis. Each point represents 1 gene with detectable expression in both phases. Genes with significant differential expression between the early secretory and mid-secretory endometria (with both a P-value <0.05 and fold-change ≥2) are plotted in red. Genes that did not exhibit significant differential expression between the two phases are shown in gray. ADRA2A, adrenoceptor alpha 2A; IRAK2, interleukin 1 receptor-associated kinase 2; TMEM37, transmembrane protein 37; AD¬AMTS15, a disintegrin and metalloproteinase with thrombospondin type 1 motifs, 15; GLB1L2, galactosidase beta 1 like 2; SERPINE1, serpin family E member 1; ITGB3, integrin subunit beta 3; TMEM252, transmembrane protein 252; RND3, Rho family GTPase 3; HAP1, huntingtin associated protein 1; ITGA2, integrin subunit alpha 2; ADAMTS8, a disintegrin and metalloproteinase with thrombospondin type 1 motifs, 8; MAOA, monoamine oxidase A; C2CD4A, C2 calcium dependent domain containing 4A.

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