Non-Coding RNAs in Endometrial Physiopathology

Ferlita, Alessandro La; Battaglia, Rosalia; Andronico, Francesca; Caruso, Salvatore; Cianci, Antonio; Purrello, Michele; Pietro, Cinzia Di

doi:10.3390/ijms19072120

Cited by 81 publications

(62 citation statements)

References 189 publications

(211 reference statements)

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“…Intriguingly, results generated by Ingenuity Pathway Analysis software revealed that E2-regulated genes were enriched with terms related to cancer diseases. Indeed, endometrioid type endometrial cancers (EEC), which represent around 70-80% of all endometrial cancers, are associated with increasing estrogen levels that, in turn are responsible for impaired control of cell proliferation (reviewed in [84]). Using the Hec-1A endometrial cancer cell line it has been demonstrated that diacylglycerol kinase alpha (DGKA) activity is required for E2-stimulated cell proliferation, as using DGKA inhibitors resulted in E2-stimulated proliferation and growth of Hec-1A cells [85].…”

Section: Involvement Of Estrogen Signaling In Processes Related To Cementioning

confidence: 99%

Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo

Kaczyński

Bauersachs

Baryla

et al. 2020

IJMS

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Estradiol-17β (E2) is a key hormone regulating reproductive functions in females. In pigs, E2, as the main conceptus signal, initiates processes resulting in prolonged corpus luteum function, embryo development, and implantation. During early pregnancy the endometrium undergoes morphological and physiological transitions that are tightly related to transcriptome changes. Recently, however, the importance of E2 as a primary conceptus signal in the pig has been questionable. Thus, the aim of the present study was to determine the effects of E2 on the porcine endometrial transcriptome in vivo and to compare these effects with transcriptome profiles on day 12 of pregnancy. Microarray analysis revealed differentially expressed genes (DEGs) in response to E2 with overrepresented functional terms related to secretive functions, extracellular vesicles, cell adhesion, proliferation and differentiation, tissue rearrangements, immune response, lipid metabolism, and many others. Numerous common DEGs and processes for the endometrium on day 12 of pregnancy and E2-treated endometrium were identified. In summary, the present study is the first evidence for the effect of E2 on transcriptome profiles in porcine endometrium in vivo in the period corresponding to the maternal recognition of pregnancy. The presented results provide a valuable resource for further targeted studies considering genes and pathways regulated by conceptus-derived estrogens and their role in pregnancy establishment.During early pregnancy in the pig, porcine conceptuses (embryos with associated membranes) secrete E2, which is regarded as the pregnancy recognition signal required for prolonged progesterone synthesis and secretion by corpora lutea (CLs). Porcine conceptuses secrete estrogens in a biphasic manner-the first increase of conceptus-derived estrogens occurs on days 11-13 after fertilization and the second is between days 15 and 25-30 after fertilization (reviewed in [2]). However, the levels of conceptus-derived estrogens in the uterine lumen may also vary depending on the number of conceptuses [1]. The period of elevated E2 synthesis and secretion by porcine conceptuses between days 11-13 of pregnancy is a process defined as the maternal recognition of pregnancy [5]. This is the critical period for establishment and development of pregnancy as the highest mortality rate of embryos in animals including pigs is observed during the peri-implantation period [6]. Embryonic estrogen synthesis and secretion not only prolongs the CL lifespan but also enhances P4-induced endometrial receptivity for implantation. Following the decrease of the progesterone receptor expression in the endometrial luminal and glandular epithelia, the expression of the estrogen receptor (ESR1) is up-regulated in these structures, which in turn is important for the cell-specific responses to conceptus estrogens released on day 12 of pregnancy [7]. Estrogen is involved in stimulation of uterine secretory activity [8], increased blood flow [9], endometrial edema [10], and the regul...

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Section: Involvement Of Estrogen Signaling In Processes Related To Cementioning

confidence: 99%

Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo

Kaczyński

Bauersachs

Baryla

et al. 2020

IJMS

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“…We encourage the scientific community consider the aforementioned tissues to compliment the conclusions of this systematic review. For example, an interesting study by Ferlita et al discussed the function of non-coding RNAs (including miRNAs) in endometrial physiology, analyzing their role in endometrial pathologies, such as endometrial cancer, endometriosis, and chronic endometritis [53]. Moreover, mounting evidence suggests that epigenetic changes may play a vital role in both placental-induced diseases, such as pre-eclampsia, and intrauterine growth restriction [54,55].…”

Section: Looking Beyond the Present Systematic Reviewmentioning

confidence: 99%

The Expression of miRNAs in Human Ovaries, Oocytes, Extracellular Vesicles, and Early Embryos: A Systematic Review

Salas‐Huetos

James

Aston

et al. 2019

Cells

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The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.

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“…Another inhibitor, estradiol-3-O-sufamate (E2MATE) used on human endometrial explants and in a mouse model of endometriosis has shown some promising results [106]. but have yet to be tested as a treatment for women with EC or endometriosis.…”

Section: Intracrinology and Metabolismmentioning

confidence: 99%

Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders

Gibson¹,

Simitsidellis²,

Collins³

et al. 2018

Preprint

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Peripheral tissue metabolism of steroids (intracrinology) is now accepted as a key way in which tissues, such as the endometrium, can utilize inactive steroids present in the blood to respond to local physiological demands and ‘fine-tune’ the activation or inhibition of steroid hormone receptor-dependent processes. Expression of enzymes that play a critical role in activation and inactivation of bioactive oestrogens (E1, E2) and androgens (A4, T, DHT), as well as expression of steroid hormone receptors, has been detected in endometrial tissues and cells recovered during the menstrual cycle. There is robust evidence that increased expression of aromatase is important for creating a local microenvironment that can support a pregnancy. Measurement of intra-tissue concentrations of steroids using liquid chromatography–tandem mass spectrometry has been important in advancing our understanding of a role for androgens in the endometrium acting both as active ligands for the androgen receptor and as substrates for oestrogen biosynthesis. The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women’s health disorders such as endometriosis and endometrial cancer has prompted renewed interest in development of drugs targeting these pathways opening up new opportunities for targeted therapies and precision medicine.   

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Non-Coding RNAs in Endometrial Physiopathology

Cited by 81 publications

References 189 publications

Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo

Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo

The Expression of miRNAs in Human Ovaries, Oocytes, Extracellular Vesicles, and Early Embryos: A Systematic Review

Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders

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