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• Self-controlled study of PRP effects on endometrial thickness in menstrual cycles. • PRP increases key endometrial biomarkers: HOXA-10, Ki67, and αvβ3 integrin. • PRP treatment significantly increased endometrial thickness. • Two successful pregnancies post-PRP suggest improved fertility potential. Thin endometrium (TE) compromises endometrial receptivity, often leading to implantation failure and lower clinical pregnancy rates. As autologous platelet-rich plasma (PRP) emerges as a potential remedy, the present study focused on its therapeutic effects on TE in infertile women who underwent frozen embryo transfer. Patients with TE who underwent frozen embryo transfer treatment in our hospital were included. To diminish individual variability, a self-controlled series approach was used. Two menstrual study cycles were arranged for each participant before the actual embryo transfer cycle; PRP treatment was conducted in the second cycle. Key metrics analyzed included endometrial thickness and the expression of specific endometrial biomarkers including HOXA-10, Ki67, and αvβ3 integrin. Transvaginal ultrasound was employed to measure endometrial thickness on Days 11 and 14, and an endometrial biopsy was conducted on progesterone Day 5 of the first two cycles. Pregnancy outcomes were observed after the embryo transfer cycle. PRP treatment significantly increased the median endometrial thickness, from 5.8 mm to 6.5 mm (P = 0.0066). Additionally, PRP treatment resulted in a statistically significant increase in the H-score for all endometrial markers. Importantly, during the subsequent embryo transfer cycle with PRP treatment, two patients successfully achieved pregnancies, both culminating in live births. These findings emphasize the potential of PRP in improving endometrial conditions, especially for individuals grappling with thin endometrium issues, as underscored by this self-comparison methodology. [ABSTRACT FROM AUTHOR]

Context: Polycystic ovary syndrome (PCOS) is an important cause of infertility. In women with PCOS have increased rate of spontaneous abortion and reduced rate of conception. HOXA–10 and HOXA–11 are proteinous products of homeobox gene group and play an important role during implantation. Aims: The aim of this study was to evaluate endometrial receptivity by measuring HOXA–10, HOXA–11, and leukemia inhibitory factor (LIF) gene expressions in women with PCOS. Settings and Design: A tertiary referral center. Materials and Methods: This study was conducted on reproductive age women with abnormal uterine bleeding without sonographically proven anatomical reason. Endometrial sampling procedures were done in proliferative phase using low-pressure endometrial suction device to exclude endometrial pathology. HOXA–10, HOXA–11, and LIF gene expressions were measured from endometrial sampling material. Blood sample was taken to measure serum estradiol level on the day of endometrial sampling. Statistical Analysis Used: Statistical analysis was performed using SPSS software version 17 (SPSS Inc., Chicago, IL, USA). Mann–Whitney U-test was used to compare the variables. Results: A total of 53 patients were included in this study. Study group consisted of 33 patients with PCOS. Gene expressions of HOXA–10, HOXA–11, and LIF were significantly lower in patients with PCOS (P < 0.05). Conclusions: This study results showed that in patients with PCOS have decreased gene expression of HOXA-10, HOXA-11, and LIF which might contribute PCOS-related infertility.

Background: Implantation failure has long been identified as a common problem underlying low success rate of IVF. Currently, endometrial receptivity has gained expert attention as it is demonstrated to contribute to successful embryo implantation. MicroRNAs (miRNAs) is known to affect endometrial receptivity through posttranscriptional gene expression regulation. This study aimed to evaluate the expression of miRNA 135b and HOXA-10 during the implantation window in endometrial tissue of infertile women. Methods: A total of 14 patients diagnosed with infertility in the gynaecology clinic of Cipto Mangunkusumo and Daya Medika hospitals Jakart, Indonesia were selected as the observed group, and 9 fertile patients were enrolled in the control group. Total RNA was isolated from endometrial tissues collected at the secretory phase of the menstrual cycle. The miRNA 135b and HOXA-10 mRNA expression were measured using quantitative real-time PCR (qPCR). The correlation between these variables was then determined using Pearson's correlation coefficient. Results: The expression of miRNA 135b in the infertile group was significantly higher by 1.81-fold compared to the control group (p<0.01), whereas, expression of HOXA-10 mRNA was significantly lower in the infertile group compared to the controls (p=0.047). Significant negative correlation was observed between the expression of miRNA 135b and HOXA-10 mRNA in infertile women (p=0.021; r=- 0.607). Conclusion: Taken together, this study provides that alteration of miRNA expression is involved in regulating the implantation process partly via modulation of the expression of gene required for implantation. [ABSTRACT FROM AUTHOR]

Context: Polycystic ovary syndrome (PCOS) is an important cause of infertility. In women with PCOS have increased rate of spontaneous abortion and reduced rate of conception. HOXA–10 and HOXA–11 are proteinous products of homeobox gene group and play an important role during implantation. Aims: The aim of this study was to evaluate endometrial receptivity by measuring HOXA–10, HOXA–11, and leukemia inhibitory factor (LIF) gene expressions in women with PCOS. Settings and Design: A tertiary referral center. Materials and Methods: This study was conducted on reproductive age women with abnormal uterine bleeding without sonographically proven anatomical reason. Endometrial sampling procedures were done in proliferative phase using low-pressure endometrial suction device to exclude endometrial pathology. HOXA–10, HOXA–11, and LIF gene expressions were measured from endometrial sampling material. Blood sample was taken to measure serum estradiol level on the day of endometrial sampling. Statistical Analysis Used: Statistical analysis was performed using SPSS software version 17 (SPSS Inc., Chicago, IL, USA). Mann–Whitney U-test was used to compare the variables. Results: A total of 53 patients were included in this study. Study group consisted of 33 patients with PCOS. Gene expressions of HOXA–10, HOXA–11, and LIF were significantly lower in patients with PCOS (P < 0.05). Conclusions: This study results showed that in patients with PCOS have decreased gene expression of HOXA-10, HOXA-11, and LIF which might contribute PCOS-related infertility. [ABSTRACT FROM AUTHOR]

In fertile women, HOXA-10 and HOXA-11 expression rises during the luteal phase, with the peak occurring during the implantation window, and stays at a high level until the end of the cycle. We evaluated the transcript and protein levels of HOXA-10 and HOXA-11 in the endometria of patients with idiopathic infertility (n = 15) and control patients (n = 10). The amounts of mRNA were determined by reverse transcription and real-time quantitative PCR. The protein levels were evaluated by Western blotting analysis. Using immunohistochemical techniques, we compared the localization of HOXA-10 and HOXA-11 proteins in the implantation window between the study and control groups. We observed statistically significantly decreased HOXA-10 and HOXA-11 transcript levels (p = 0.003, p = 0.012 respectively) in infertile patients compared to controls. There was no significant decrease in HOXA-10 protein levels between these groups (p = 0.074). However, we observed a significantly higher level of HOXA-11 protein in the endometria of infertile patients compared to controls (p = 0.015). HOXA-10 and HOXA-11 proteins were localized in the nuclei of the endometrial stromal cells. Immunohistochemical analyses did not reveal differences between amounts of HOXA-10 and HOXA-11 protein levels in infertility and control groups. Our results suggest that HOXA-10 and HOXA-11 gene expression in the endometrium during the implantation window may not be altered in patients with idiopathic infertility. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 111–118)

Purpose: The outcomes of in-vitro maturation (IVM) are inferior compared to those of IVF. The purpose of the study was to compare the implantation rates of IVM- and in-vivo maturation (IVO)- derived embryos, and to evaluate their effects on uterine receptivity. Methods: The IVM- and IVO- oocytes were obtained from female mice, fertilized and transferred to separate oviducts of the same pseudo-pregnant mice. After 5 days, the implanted blastocysts were dissected out of the uterine horns, and the uterine horns were analyzed for the expression of mRNAs encoding leukemia inhibitory factor, heparin-binding epidermal growth factor, insulin-like growth factor binding protein-4, progesterone receptor, and Hoxa-10. Results: The maturation rate of the IVM- oocytes was 81.2 %. The fertilization rate of the IVM oocytes was lower than that of the IVO oocytes (50.5 % vs. 78.0 %, p = 0.038), as was their implantation rate (14.5 % vs. 74.7 %, p < 0.001). All 5 mRNAs examined were expressed at significantly lower levels in the uterine horns that received the IVM-derived embryos than in those that received the IVO-derived embryos. Conclusions: The IVM-derived embryos are less competent in inducing expression of implantation-related mRNAs in the uterine horn. [ABSTRACT FROM AUTHOR]

In fertile women, HOXA-10 and HOXA-11 expression rises during the luteal phase, with the peak occurring during the implantation window, and stays at a high level until the end of the cycle. We evaluated the transcript and protein levels of HOXA-10 and HOXA-11 in the endometria of patients with idiopathic infertility (n = 15) and control patients (n = 10). The amounts of mRNA were determined by reverse transcription and real-time quantitative PCR. The protein levels were evaluated by Western blotting analysis. Using immunohistochemical techniques, we compared the localization of HOXA-10 and HOXA-11 proteins in the implantation window between the study and control groups. We observed statistically significantly decreased HOXA-10 and HOXA-11 transcript levels (p = 0.003, p = 0.012 respectively) in infertile patients compared to controls. There was no significant decrease in HOXA-10 protein levels between these groups (p = 0.074). However, we observed a significantly higher level of HOXA-11 protein in the endometria of infertile patients compared to controls (p = 0.015). HOXA-10 and HOXA-11 proteins were localized in the nuclei of the endometrial stromal cells. Immunohistochemical analyses did not reveal differences between amounts of HOXA-10 and HOXA-11 protein levels in infertility and control groups. Our results suggest that HOXA-10 and HOXA-11 gene expression in the endometrium during the implantation window may not be altered in patients with idiopathic infertility. [ABSTRACT FROM AUTHOR]

Abstract: Endometriosis is a chronic gynecological disease characterized by the growth of endometrial tissue outside the uterine cavity. Exposure to endocrine disruptors during critical period of development causes long-lasting effects, being the genital system one of the targets. This study describes the effects on female genital system caused by developmental exposure to the endocrine-disrupting chemical bisphenol A (BPA) during pre- and peri-natal development in mice. To this end, timed pregnant Balb-C mice were treated from day 1 of gestation to 7days after delivery with BPA (100, or 1000μg/kg/day). After delivery, pups were held for 3 months; then, pelvic organs were analyzed in their entirety and livers of both pups and moms were studied for the presence of BPA. We found in the adipose tissue surrounding the genital tracts of a consistent number of treated animals, endometriosis-like structure with the presence of both glands and stroma and expressing both estrogen receptor and HOXA-10. Moreover, cystic ovaries, adenomatous hyperplasia with cystic endometrial hyperplasia and atypical hyperplasia were significantly more frequent in treated animals respect to the controls. Finally, BPA was found in the livers of exposed moms and female offspring. In conclusion, we describe for the first time an endometriosis-like phenotype in mice, elicited by pre-natal exposition to BPA. This observation may induce to thoroughly reconsider the pathogenesis and treatment of endometriosis, considering the high incidence of endometriosis and the problems caused by associated infertility. [ABSTRACT FROM AUTHOR]

Abstract: Uterine decidualization, a key event for successful implantation, is critically controlled by stromal cell proliferation and differentiation. One hallmark event of decidualization is the acquisition of stromal cell polyploidy through terminal differentiation at the anti-mesometrial pole of the implantation site. Hoxa-10, a developmentally regulated homeobox transcription factor, is highly expressed in decidualizing stromal cells, and targeted deletion of Hoxa-10 in mice shows severe decidualization defects, primarily due to reduced stromal cell responsiveness to progesterone. However, the underlying molecular mechanism by which Hoxa-10 regulates this process remains largely unknown. Here, we show that Hoxa-10 deficiency confers diminished core cell cycle activity during stromal cell proliferation without disturbing polyploidy, suggesting that these events depend on local regulators that impact cell cycle machinery. To further address this question, we compared global gene expression profiles in uteri of wild-type and Hoxa-10 −/− mice after inducing decidualization. Our studies show two major aspects of decidualization downstream of Hoxa-10. First, Hoxa-10 deficiency results in the aberrant region-specific expression of cyclin-dependent kinase-4 (cdk4) and -6 (cdk6), growth differentiation factor 10 (Gdf10), hepatocyte growth factor (Hgf) and Snail2. Second, Hoxa-10 deficiency compromises natural killer (NK) cell differentiation without altering trafficking of NK precursor cells during decidualization. Collectively, the results provide evidence that Hoxa-10 influences a host of genes and cell functions necessary for propagating normal decidual development during the post-implantation period. [Copyright &y& Elsevier]

• Stanozolol (AAS) disrupts estrous cycle in mice and its recovery is dose dependent. • Low dose ST treated mice maintained gestation till term with reduced litter size. • Neither doses affected preimplantation embryo development and blastocyst hatching. • High dose lowers endometrial expression of ERα, PR, LIF, Hoxa-10 & intensifies PRLR. • High dose of ST impedes embryo implantation by attenuating endometrial receptivity. The present investigation is aimed at evaluating the efficacy of one of the anabolic –androgenic steroids, stanozolol (ST), on establishment and maintenance of pregnancy in mice. A total of 40 female mice were assigned to three experimental groups. Stanozolol was dosed subcutaneously (low-dose, 0.5 mg/kg bwt; high-dose, 5.0 mg/kg bwt or 1% alcohol-baseline control) for 30 consecutive days. On the 31st day, treatment was withdrawn. The estrous cycle was disrupted in both treatment groups and its resumption was dose dependent. Following estrous resumption, mice were allowed to mate. Results reveal that the low-dose ST-treated mice maintained gestation until term with reduced litter size, while high-dose-treated mice divulged vaginal plug at frequent intervals, indicating conception failure. Because pregnancy failure was noticed in high-dose-treated mice, they were autopsied on GD1.5 and 4.5. Interestingly, neither dose of stanozolol affected early embryonic development or blastocyst hatching. A decrease in the number of corpora lutea in both treated groups suggests it affects either ovulation or recruitment of follicles that occurs in each cycle for maturation. In high-dose-treated mice, decreased serum levels of estradiol, progesterone and increased testosterone along with downregulated endometrial expression of ERα and PR suggest the deficiency of steroid hormones and their respective receptors. Decreased ovarian expression of ERα, hyperexpression of PRLR, AR and abated progesterone secretion led to luteal dysfunction, consequently attenuating endometrial receptivity. Therefore, in high-dose-treated mice, decreased maternal estradiol and progesterone levels and their receptors during implantation hindered signaling to LIF and Hoxa-10, resulting in pragmatic implantation failure. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate endometrial receptivity by measuring HOXA-10, HOXA-11, and LIF gene expressions in women with polycystic ovary syndrome., Methods: A total of 48 women were included in this clinical study. Thepatients were allocated to two groups: study group consisted of 28 patients with myoma uteri and control group consisted of 20 patients without myoma uteri. Endometrial sampling was performed during the proliferative phase. The biopsies obtained from the patients with myoma uteri were taken from the place where the fibroids were localized. HOXA-10, HOXA-11, and LIF expressions were measured in the endometrial sampling material. Demographic data of the patients such as age, obstetric and gynecologic history, medical conditions, medications, surgical history, last menstrual period were recorded. Also, the number, size, localization, and type of the myoma were registered., Results: The mean age of the patients was 42.07 and 38.17, respectively. HOXA-11 levels in the study and control groups were 0.004 ± 0.001 and 0.010 ± 0.001, respectively ( P < 0.90). Paradoxically, HOXA-10 levels were found to be higher in the study group than the control group, but the difference was not statistically significant ( P < 0.25). LIF levels were significantly lower in the study group ( P < 0.05)., Conclusion: Our results showed that myoma uteri might lead to a decrease in implantation rate by diminishing LIF gene expressions. However, there were no differences between the two groups in terms of HOXA-10 and HOXA-11 levels., (© 2018 Wiley Periodicals, Inc.)

Objective: To compare the expression of HOXA-10 and E-cadherin in the endometrium of women with recurrent implantation failure (RIF), women with recurrent miscarriage (RM), and women with proven fertility (normal control; NC).Design: Observational cohort study.Setting: University assisted reproductive unit.Patient(s): Fifty women were recruited: 18 NC, 12 unexplained RIF, and 20 RM.Interventions(s): None.Main Outcome Measure(s): Endometrial biopsy was precisely timed 7 days after LH surge. The expression of HOXA-10 and E-cadherin were examined by means of immunohistochemistry. H-Scores of staining intensity in the glandular epithelium and stroma were measured.Result(s): HOXA-10 signal was mainly localized in the nuclei of stroma cells and the cytoplasm of glandular epithelium cells. E-Cadherin signal was found only in the cytoplasm of glandular epithelium cells. The HOXA-10 H-scores in the RIF group and the RM group were significantly lower than in the control group in both the glandular epithelium and stroma. The E-cadherin H-scores in the RM group were also significantly lower than in the control group. Interestingly, there was a positive correlation between HOXA-10 and E-cadherin H-scores in all of the women examined.Conclusion(s): There is a positive correlation between levels of HOXA-10 and E-cadherin expression in the endometrium, both of which are significantly reduced in women with RIF and RM compared with fertile control women. The findings suggest a potential role of HOXA-10 and E-cadherin in the implantation processes and altered expression in women with reproductive failure. [ABSTRACT FROM AUTHOR]