The roles and expression of HOXA/Hoxa10 gene: A prospective marker of mammalian female fertility?

Ekanayake, Don Lochana; Małopolska, Martyna; Schwarz, Tomasz; Tuz, R.; Bartlewski, Pawel M.

doi:10.1016/j.repbio.2022.100647

Cited by 16 publications

(11 citation statements)

References 20 publications

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“…Female mice lacking HOXA10 have been reported to experience spontaneous abortion and infertility owing to implantation and decidualization failure [ 59 ]. HOXA10 expression is associated with variations in the expressions of downstream target genes, including ITGB3, which are biomarkers of endometrial receptivity [ 60 ]. The expression of ITGB3 increases in the mid-secretory phase, which corresponds to WOI.…”

Section: Discussionmentioning

confidence: 99%

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells

Wang,

Gao,

Yao

et al. 2024

Reprod Biol Endocrinol

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Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells

Wang,

Gao,

Yao

et al. 2024

Reprod Biol Endocrinol

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“…HOXA10 is a transcription factor that plays a crucial role in the functional differentiation of the endometrium [ 18 ]. HOXA10 is highly expressed in the endometrium’s luminal epithelium, glandular epithelium, and stroma cells.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of HOXA10 in a specific tissue has been associated with several diseases, including endometrial cancer [ 14 , 15 ], prostate cancer [ 16 ], acute myeloid leukemia [ 14 ], gastric cancer [ 17 ], and many other cancers. In endometriosis, HOXA10 has been proposed as one of the potential biomarkers for the diagnosis of endometriosis [ 18 ]. The loss of HOXA10 expression has been reported to cause endometrial hyperplasia leading to endometrial cancer [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review

Elias

Lazim

Sutaji

et al. 2023

Biology

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Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR “homeobox A10” OR “HOXA-10” OR HOX1) AND (“DNA methylation” OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.

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“…Our mesoscale chromatin model has high-resolution particles (9-bp), so it is compatible with Micro-C, which can have resolution as high as 100 bp. Three sets of data are obtained for five gene systems as follows: (i–iii) the NXN ( 54 ), HOXC ( 55 , 56 ) and HOXA ( 57 , 58 ) genes in mouse embryonic stem cells (mESC). We focused on these three regions for validation purposes using Micro-C data from ( 53 ) (GEO accession: GSE130275) with 100 bp resolution.…”

Section: Methodsmentioning

confidence: 99%

Hi-BDiSCO: folding 3D mesoscale genome structures from Hi-C data using brownian dynamics

Li,

Schlick

2023

Nucleic Acids Research

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The structure and dynamics of the eukaryotic genome are intimately linked to gene regulation and transcriptional activity. Many chromosome conformation capture experiments like Hi-C have been developed to detect genome-wide contact frequencies and quantify loop/compartment structures for different cellular contexts and time-dependent processes. However, a full understanding of these events requires explicit descriptions of representative chromatin and chromosome configurations. With the exponentially growing amount of data from Hi-C experiments, many methods for deriving 3D structures from contact frequency data have been developed. Yet, most reconstruction methods use polymer models with low resolution to predict overall genome structure. Here we present a Brownian Dynamics (BD) approach termed Hi-BDiSCO for producing 3D genome structures from Hi-C and Micro-C data using our mesoscale-resolution chromatin model based on the Discrete Surface Charge Optimization (DiSCO) model. Our approach integrates reconstruction with chromatin simulations at nucleosome resolution with appropriate biophysical parameters. Following a description of our protocol, we present applications to the NXN, HOXC, HOXA and Fbn2 mouse genes ranging in size from 50 to 100 kb. Such nucleosome-resolution genome structures pave the way for pursuing many biomedical applications related to the epigenomic regulation of chromatin and control of human disease.

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The roles and expression of HOXA/Hoxa10 gene: A prospective marker of mammalian female fertility?

Cited by 16 publications

References 20 publications

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells

HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review

Hi-BDiSCO: folding 3D mesoscale genome structures from Hi-C data using brownian dynamics

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