Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers

被引：185

作者：

Altmae, Signe ^{[1
,2
,3
,4
]}

Koel, Mariann ^{[3
,5
,6
,7
]}

Vosa, Urmo ^{[8
]}

Adler, Priit ^{[9
]}

Suhorutsenko, Marina ^{[3
,10
]}

Laisk-Podar, Triin ^{[3
,10
]}

Kukushkina, Viktorija ^{[3
]}

Saare, Merli ^{[3
,10
]}

Velthut-Meikas, Agne ^{[3
]}

Krjutskov, Kaarel ^{[3
,5
,6
]}

Aghajanova, Lusine ^{[11
]}

Lalitkumar, Parameswaran G. ^{[1
,2
]}

Gemzell-Danielsson, Kristina ^{[1
,2
]}

Giudice, Linda ^{[11
]}

Simon, Carlos ^{[12
,13
]}

Salumets, Andres ^{[3
,10
,14
,15
]}

机构：

[1] Karolinska Inst, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, S-17176 Stockholm, Sweden

[2] Karolinska Univ Hosp, S-17176 Stockholm, Sweden

[3] Competence Ctr Hlth Technol, EE-50410 Tartu, Estonia

[4] Univ Granada, Dept Biochem & Mol Biol, Fac Sci, Granada 18016, Spain

[5] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden

[6] Karolinska Inst, Ctr Innovat Med, S-14183 Huddinge, Sweden

[7] Univ Tartu, Dept Cell Biol, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia

[8] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia

[9] Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia

[10] Univ Tartu, Dept Obstet & Gynaecol, Inst Clin Med, EE-51014 Tartu, Estonia

[11] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA

[12] Univ Valencia, Dept Obstet & Gynaecol, Valencia 46021, Spain

[13] INCLIVA, Igenom & Fdn 41, Valencia 46021, Spain

[14] Univ Helsinki, Dept Obstet & Gynecol, FL-00029 Helsinki, Finland

[15] Helsinki Univ Hosp, FL-00029 Helsinki, Finland

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION ANALYSIS; ALPHA-V-BETA-3; INTEGRIN; IMPLANTATION FAILURE; EMBRYO IMPLANTATION; MENSTRUAL-CYCLE; EUTOPIC ENDOMETRIUM; UTERINE RECEPTIVITY; MICRORNA EXPRESSION; HORMONAL-REGULATION; CANDIDATE GENES;

D O I：

10.1038/s41598-017-10098-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up-and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from 'pre-receptive' and 88 from mid-secretory, 'receptive' phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.

引用

页数：15

共 116 条

[31] Clinical approaches to increasing uterine receptivity during human implantation [J].