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Mother and Embryo Cross Communication during Conception
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Anna Idelevich, Andrea Peralta, Felipe Vilella
Homeobox protein A10, A11 (HOXA10, HOXA11) play a role in decidualization, and their deletion in mice results in implantation defects [122,123]. HOXA10-null mice produce normal numbers of embryos that are able to implant in wild-type surrogate mice, whereas wild-type embryos from the surrogate mice cannot implant in the HOXA10-null mice [122,124]. HOXA11−/− mice show similar phenotype related to implantation [125]. In the human endometrium, HOXA10 is expressed by both epithelial and stromal cells in a menstrual cycle-dependent manner and is regulated by progesterone [126]. Microarray analysis of murine endometrium transfected with HOXA10 cDNA identified 40 downstream target genes including clusterin (Clu), phosphoglycerate 3-dehydrogenase (3-Pgdh), and tumor-associated calcium signal transducer 2 (Tacstd2) [127].
Causes of Bleeding
Published in John C. Petrozza, Uterine Fibroids, 2020
Ophelia Yin, Carter M. Owen, Kamaria Cayton, James H. Segars
While most prior studies have focused on comparing fibroids to myometrium, there are new data on how fibroids may directly affect the endometrium. Rackow and Taylor [24] compared the homeobox A10 (HOXA10) gene and protein expression in endometrial biopsies from 30 reproductive-age women with submucosal, intramural or no uterine fibroids in the proliferative phase of their menstrual cycle. HOXA10 is a homeobox-containing transcription factor necessary for promoting stromal decidualization and leukocyte infiltration during each menstrual cycle [25]. Endometrial samples from submucosal uteri had lower HOXA10 expression compared with both endometrium from control patients and patients with intramural fibroids. Of utmost significance, within the same uterus, there was no difference in HOXA10 mRNA expression in endometrial biopsies taken directly over a submucosal myoma compared to endometrium remote from the fibroid. These findings support the principle that fibroids can have both a focal and a global effect on the endometrium.
Infertility attributed to endometriosis
Published in Seema Chopra, Endometriosis, 2020
Shalini Gainder, Neethi Mala Mekala
One of the examples of aberrant gene expression is the Hoxa 10/HOXA10 gene. It is a gene which is associated with embryogenesis of the uterus and in regeneration of the endometrium in every menstrual cycle, and its expression is necessary for endometrial receptivity in women. Its expression peaks during the period of implantation under the influence of progesterone and estrogen. Women with endometriosis do not show expected mid-luteal rise, which may partially describe their infertility [6,7].
Progress of oxidative stress in endometrium decidualization
Published in Journal of Obstetrics and Gynaecology, 2022
Wenxin Gao, Fei Feng, Xiaoling Ma, Rui Zhang, Lifei Li, Feng Yue, Meng Lv, Lin Liu
RIF refers to the failure of embryo implantation in three or more consecutive cycles of in vitro fertilisation and embryo transfer (IVF-ET), and there are one to two high quality embryos in per cycle (Bashiri et al.2018). The occurrence of RIF may be related to many factors, including abnormal anatomical structure of uterus, genetic defects of embryo, disorder of hormone and metabolism, infection, immune factors and so on (Timeva et al.2014). Transcription factor FOXOs family is the key regulator of decidualization (Brosens et al.2009). There was confirmed that the expression of KLF12, a negative regulator of decidualization, increased in the endometrium of patients with RIF, and directly combined with the FOXO1 promoter region and inhibited its expression in ESCs, resulting in decidualization disorder (Zhang et al.2015). This result indicates that there is a certain degree of decidual disorder in patients with RIF. HOXA10 is also an important regulator of decidualization of human endometrium (Taylor et al.1998). It has been shown that HOXA10 can be ubiquitin-modified on lysine 164residues, and the resulting SUMO1-HOXA10 may lead to decidualization defects and then affect embryo implantation. The level of SUMO1-HOXA10 in secretory endometrium of RIF patients was significantly higher than that of normal women of childbearing age (Jiang et al.2017), which further confirmed that decidualization defect could lead to RIF.
Zooming in on the endometrial factor of recurrent implantation failure
Published in Human Fertility, 2022
Chibuzor Ifenatuoha, Babatunde Okewale
The Müllerian ducts are paired structures formed during embryonic development that give rise to the uterus, Fallopian tubes, uterine cervix, and the anterior part of the vagina (Robboy et al., 2017). Typically, the formation of the Müllerian duct takes in three phases, which are: (i) organogenesis (when the ducts are formed); (ii) fusion (when the ducts fuse to form the uterus); and (iii) septal resorption (when the central septum is finally resorbed after the fusion of the ducts). Any anomaly that would result in the failure of completion of the organogenesis phase may result in uterine agenesis, hypoplasia, or a unicornuate uterus. Similarly, the failure in completion of the fusion and septal resorption phases will result in a bicornuate or didephys uterus and a septate or arcuate uterus respectively (Chandler et al., 2009). It was estimated that about 3.8 to 9.6% of the general population have abnormal uterine formation (Santamaria et al., 2018). Mutation in the homeobox genes (HOXA10 and HOXA11) are said to be responsible for Mullerian duct malformation. The homeobox gene family is commonly responsible for the regulation of the Müllerian duct formation. In addition, the HOXA10 and HOXA11 are said to also play a role in endometrial development and preparing the endometrium for implantation (Coughlan et al., 2014).
Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis
Published in Systems Biology in Reproductive Medicine, 2022
Jing Zhang, Lihui Wang, Chunyan Li, Hui Zhang, Rui Li, Mingjiang Li
HOXA10, a member of the homeobox (HOX) family, is expressed in the nucleus of endometrial glands and stroma of the endometrium (Gui et al. 1999). Its expression depends on the stage of the menstrual cycle, dramatically increasing at the time of implantation (Taylor et al. 1998; Gui et al. 1999). The expression of HOXA10 is altered in the endometrium of women with infertility, such as patients with endometriosis and polycystic ovary syndrome (Cermik et al. 2003). Previous studies have shown that HOXA10 regulates the expression of ITGB3, which encoding integrin αvβ3, affects endometrial receptivity. HOXA10 activates reporter gene expression via a 41-bp β3-Integrin subunit element containing two of the four HOXA10 binding sites (Daftary et al. 2002). In addition, HOXA10 can alter embryo viability by regulating tryptophan 2,3-dioxygenase through serotonin signaling (Doherty et al. 2011). The elevated expression of HOXA10 promotes the expression of integrin αvβ3 and enhances embryo vitality, promoting embryo implantation.