scholarly journals Endometrial delay is found to be part of a normal individual dynamic transformation process

2021 ◽  
Author(s):  
Joachim Alfer ◽  
Roxana M. Popovici ◽  
Amir Fattahi ◽  
Jürgen Krieg ◽  
Ralf Dittrich ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Normal Individual ◽  
Hormone Replacement ◽  
Transformation Process ◽  
Endometrial Receptivity ◽  
Transformation Rate ◽  
Limited Information ◽  
Secretory Phase ◽  
Ki 67 ◽  
Dynamic Transformation

Abstract Purpose Limited information is clinically available concerning endometrial receptivity; assessing endometrial transformation status is therefore an urgent topic in assisted reproductive technology. This study aimed to investigate individual endometrial transformation rates during the secretory phase in subfertile patients using personal endometrial transformation analysis. Methods Monitoring was carried out during the secretory phase to obtain endometrial receptivity profiles. For the investigation, two endometrial biopsies were taken within one menstrual cycle. The extended endometrial dating was based on the Noyes criteria, combined with immunohistochemical analyses of hormone receptors and proliferation marker Ki-67. Biopsies were taken mainly at days ovulation (OV, n = 76)/hormone replacement therapy (HRT, n = 58) + 5 and + 10. Results The results of the two biopsies were correlated with the clinically expected day of the cycle and showed temporal delays or hypercompensations, diverging from the expected cycle days by 0.5–5 days. In comparison with the first biopsies, the transformation rate in the second biopsies showed compensation, augmented delay, or constant transformation in 48.69, 22.37, and 28.94% of cases for ovulation in natural cycles and 56.89, 25.85, and 17.26% for HRT cycles, respectively. Conclusion The study revealed an individually dynamic transformation process of the endometrium, with the ability to compensate or enlarge an initial “delay”, which is now identified as a normal individual transformation process during the secretory phase. This information is of great importance for the scientific investigation of dynamic changes in endometrial tissue, as well as for the timing of embryo transfers.

scholarly journals Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients?

2017 ◽  
Vol 77 (07) ◽  
pp. 756-764 ◽  
Author(s):  
Joachim Alfer ◽  
Lars Happel ◽  
Ralf Dittrich ◽  
Matthias Beckmann ◽  
Arndt Hartmann ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Steroid Hormone ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Steroid Hormone Receptors ◽  
Uterine Disease ◽  
Secretory Phase ◽  
Ki 67 ◽  
Tissue Samples ◽  
Thin Endometrium

Abstract Introduction This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected. Methods To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls. The tissue samples were investigated for steroid hormone receptor expression and for the proliferation marker Ki-67. Immunohistochemistry was performed with antibodies against the marker molecules for endometrial receptivity – β3 integrin, VEGF, LIF, and CD56 (large granular lymphocytes, LGLs). Results The steroid hormone receptors for estrogen (E2) and progesterone (P) were expressed normally (at the first biopsy) and were down-regulated (at the second biopsy) within the cycle. Strikingly, all of the marker molecules investigated showed negative or weak and inadequate expression in the mid-secretory phase. Numbers of LGLs remained as low as in the proliferative phase. In contrast, fertile patients were found to express these marker molecules distinctly in the mid-secretory phase. Conclusions It may be hypothesized that a severe deficiency of these angiogenesis-related marker molecules leads to defective development of the endometrium, which remains thin. Deficient angiogenetic development may thus provide an explanation for the endometrial factor that causes infertility. Further investigations will need to focus on identifying the regulating factors that act between steroid receptor activation and the expression of these marker molecules.

scholarly journals Apoptosis, Proliferation, and Sex Hormone Receptors in Superficial Parts of Human Endometrium at the End of the Secretory Phase1

1999 ◽  
Vol 84 (5) ◽  
pp. 1737-1743 ◽  
Author(s):  
M. Dahmoun ◽  
K. Boman ◽  
S. Cajander ◽  
P. Westin ◽  
T. Bäckström
Keyword(s):  
Menstrual Cycle ◽  
Progesterone Receptor ◽  
Hormone Receptors ◽  
Apoptotic Index ◽  
Serum Samples ◽  
Secretory Phase ◽  
Ki 67 ◽  
17Β Estradiol ◽  
Menstruating Women ◽  
Endometrial Epithelium

Apoptosis with one regulator, Bcl-2, and proliferation with the marker Ki-67 were studied in 75 endometrial biopsies representing superficial parts of endometrium from 35 regularly menstruating women premenstrually and menstrually. Hormonal withdrawal was studied in serum samples and potentiated in epithelium by the decreasing 17β-estradiol and progesterone receptor scores 4 days premenstrually. The apoptotic index increased 2 days before the onset of menstruation and peaked on the second menstrual day. The high apoptotic index together with low proliferation in endometrial epithelium at the end of the menstrual cycle are similar to the involution process seen in other hormone-dependent organs. In stroma, the apo-ptotic index increased later, at the onset of menstruation, and the increase was lower than that in epithelium. The Ki-67 index increased during the last 3 days of the secretory phase, parallel with an increasing progesterone receptor score and decreasing Bcl-2 staining, and peaked at the onset of menstruation. The findings in stroma concur with high proliferation at the end of the menstrual cycle and high cell turnover during menstruation, suggesting the participation of stroma in the renewal process of endometrium.

AGE FEATURES OF MOLECULAR-BIOLOGICAL SUBTYPES OF BREAST CANCER

2020 ◽  
Vol 17 (2) ◽  
pp. 187-192
Author(s):  
E.A. Novikova ◽  
◽  
O.V. Kostromina ◽  
D.V. Mikhailov ◽  
S.L. Leontiev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Age Groups ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Age Related ◽  
Age Features ◽  
Immunohistochemical Studies ◽  
Triple Negative Subtype

Aim. The aim of the study was to determine the presence of peculiarities of the age structure in patients with various surrogate molecular biological subtypes of breast cancer. Materials and research methods. This work analyzes the age-related characteristics of the occurrence of molecular biological subtypes in 499 patients with invasive breast cancer. All cases were divided into 5 molecular biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. The average age of the patients was 53.4±0.39 years, the predominant group was patients from 50 to 60 years (37.2% of the total). Research results. In patients under 40 years old, the triple negative subtype prevailed (44.8%). Luminal A subtype prevailed in the groups 51-60 years old (more than 41.4%) and over 60 years old (39.7%). Luminal B (Her2-) subtype was equally found in all age groups.

scholarly journals MAML1: a coregulator that alters endometrial epithelial cell adhesive capacity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sadaf Zafir ◽  
Wei Zhou ◽  
Ellen Menkhorst ◽  
Leilani Santos ◽  
Evdokia Dimitriadis
Keyword(s):  
Notch Signaling ◽  
Cell Line ◽  
Notch Signaling Pathway ◽  
Endometrial Receptivity ◽  
Trophoblast Cell ◽  
Luminal Epithelium ◽  
Secretory Phase ◽  
Ishikawa Cells ◽  
Trophoblast Cell Line ◽  
Adhesive Capacity

Abstract Background Abnormalities in endometrial receptivity has been identified as a major barrier to successful embryo implantation. Endometrial receptivity refers to the conformational and biochemical changes occurring in the endometrial epithelial layer which make it adhesive and receptive to blastocyst attachment. This takes place during the mid-secretory phase of woman’s menstrual cycle and is a result of a delicate interplay between numerous hormones, cytokines and other factors. Outside of this window, the endometrium is refractory to an implanting blastocyst. It has been shown that Notch ligands and receptors are dysregulated in the endometrium of infertile women. Mastermind Like Transcriptional Coactivator 1 (MAML1) is a known coactivator of the Notch signaling pathway. This study aimed to determine the role of MAML1 in regulating endometrial receptivity. Methods The expression and localization of MAML1 in the fertile human endometrium (non-receptive proliferative phase versus receptive mid-secretory phase) were determined by immunohistochemistry. Ishikawa cells were used as an endometrial epithelial model to investigate the functional consequences of MAML1 knockdown on endometrial adhesive capacity to HTR8/SVneo (trophoblast cell line) spheroids. After MAML1 knockdown in Ishikawa cells, the expression of endometrial receptivity markers and Notch dependent and independent pathway members were assessed by qPCR. Two-tailed unpaired or paired student’s t-test were used for statistical analysis with a significance threshold of P < 0.05. Results MAML1 was localized in the luminal epithelium, glandular epithelium and stroma of human endometrium and the increased expression identified in the mid-secretory phase was restricted only to the luminal epithelium (P < 0.05). Functional analysis using Ishikawa cells demonstrated that knockdown of MAML1 significantly reduced epithelial adhesive capacity (P < 0.01) to HTR8/SVneo (trophoblast cell line) spheroids compared to control. MAML1 knockdown significantly affected the expression of classical receptivity markers (SPP1, DPP4) and this response was not directly via hormone receptors. The expression level of Hippo pathway target Ankyrin repeat domain-containing protein 1 (ANKRD1) was also affected after MAML1 knockdown in Ishikawa cells. Conclusion Our data strongly suggest that MAML1 is involved in regulating the endometrial adhesive capacity and may facilitate embryo attachment, either directly or indirectly through the Notch signaling pathway.

scholarly journals A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 574 ◽  
Author(s):  
Kadri Rekker ◽  
Signe Altmäe ◽  
Marina Suhorutshenko ◽  
Maire Peters ◽  
Juan F. Martinez-Blanch ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Blood Samples ◽  
Infertile Women ◽  
Secretory Endometrium ◽  
Fertile Women

The endometrium undergoes extensive changes to prepare for embryo implantation and microRNAs (miRNAs) have been described as playing a significant role in the regulation of endometrial receptivity. However, there is no consensus about the miRNAs involved in mid-secretory endometrial functions. We analysed the complete endometrial miRNome from early secretory (pre-receptive) and mid-secretory (receptive) phases from fertile women and from patients with recurrent implantation failure (RIF) to reveal differentially expressed (DE) miRNAs in the mid-secretory endometrium. Furthermore, we investigated whether the overall changes during early to mid-secretory phase transition and with RIF condition could be reflected in blood miRNA profiles. In total, 116 endometrial and 114 matched blood samples collected from two different population cohorts were subjected to small RNA sequencing. Among fertile women, 91 DE miRNAs were identified in the mid-secretory vs. early secretory endometrium, while no differences were found in the corresponding blood samples. The comparison of mid-secretory phase samples between fertile and infertile women revealed 21 DE miRNAs from the endometrium and one from blood samples. Among discovered novel miRNAs, chr2_4401 was validated and showed up-regulation in the mid-secretory endometrium. Besides novel findings, we confirmed the involvement of miR-30 and miR-200 family members in mid-secretory endometrial functions.

Polo-like kinase expression in normal human endometrium during the menstrual cycle

2000 ◽  
Vol 12 (2) ◽  
pp. 59 ◽  
Author(s):  
Noriyuki Takai ◽  
Tami Miyazaki ◽  
Isao Miyakawa ◽  
Ryoji Hamanaka
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Cellular Proliferation ◽  
Secretory Phase ◽  
Ki 67 ◽  
Normal Endometrium ◽  
Proliferative Phase ◽  
Normal Human ◽  
Late Secretory Phase

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% 4.98%) and the early secretory phase (19.28% 4.99%) than in the early proliferative phase (2.60% 2.33%) or the late secretory phase (5.76% 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.

scholarly journals Effect of Two-Step Austempering Process on Transformation Kinetics of Nanostructured Bainitic Steel

Materials ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 166 ◽  
Author(s):  
Chunhe Chu ◽  
Yuman Qin ◽  
Xuemei Li ◽  
Zhinan Yang ◽  
Fucheng Zhang ◽  
...  
Keyword(s):  
Activation Energy ◽  
Energy Barrier ◽  
Bainitic Ferrite ◽  
Transformation Process ◽  
Transformation Rate ◽  
Bainitic Steel ◽  
Transformation Kinetics ◽  
Activation Energy Barrier ◽  
Quenching Process ◽  
Kinetics Of

The two-step austempering process has been reported to be an effective method to accelerate the bainitic transformation process by introducing martensite (Q-M-B). However, in this study, it was found that the Q-M-B process reduced the incubation time, but the transformation duration remained nearly unchanged. The notably reduced activation energy barrier for nucleation of bainitic ferrite on the preformed martensite should be responsible for the reduced duration time of the Q-M-B process. A process that both of the two steps were above, Ms (Q-B-B), has been demonstrated to increase transformation rate and improve the amount of bainitic ferrite, which probably results from the additional hysteresis free energy provided by the first quenching process.

Structural Change and Women’s Employment Potential in Myanmar

2020 ◽  
Vol 43 (5) ◽  
pp. 450-476
Author(s):  
Valerie Mueller ◽  
Emily Schmidt ◽  
Dylan Kirkleeng
Keyword(s):  
Structural Change ◽  
Labor Force ◽  
Labor Force Participation ◽  
Well Being ◽  
Active Role ◽  
Transformation Process ◽  
Gender Pay Gap ◽  
Pay Gap ◽  
Dynamic Transformation ◽  
Employment Potential

We use the Integrated Household Living Conditions Survey to evaluate the extent women are included in Myanmar’s dynamic transformation process and the relative barriers that prohibit their inclusion between 2005 and 2010. Women play an active role in the labor force during a period of massive structural change. Their growing importance is substantiated by their increasing placement in manufacturing jobs near and away from home. Despite their increasing labor force participation, women’s engagement in manufacturing is negatively associated with household welfare. This may be a function of a gender pay gap or reflect households’ inability to substitute the labor of women to complete specific tasks related to household production. Future investments in surveys in Myanmar will improve our ability to identify which factors systematically provide an enabling environment for female labor participation, mobility, and improvements in well-being.

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