A5025845183- Reproductive System and Pregnancy
- Endometriosis Research and Treatment
- Pregnancy and preeclampsia studies
- Estrogen and related hormone effects
- Reproductive Biology and Fertility
- Uterine Myomas and Treatments
- Gynecological conditions and treatments
- FOXO transcription factor regulation
- Ectopic Pregnancy Diagnosis and Management
- Birth, Development, and Health
- Reproductive Physiology in Livestock
- Endometrial and Cervical Cancer Treatments
- Systemic Lupus Erythematosus Research
- Circular RNAs in diseases
- Assisted Reproductive Technology and Twin Pregnancy
- Maternal and fetal healthcare
- Ovarian function and disorders
- Preterm Birth and Chorioamnionitis
- Pregnancy-related medical research
- Cell Adhesion Molecules Research
- Prenatal Screening and Diagnostics
- Pregnancy and Medication Impact
- MicroRNA in disease regulation
- Cancer Mechanisms and Therapy
- Epigenetics and DNA Methylation
University of Warwick
2016-2025
University Hospitals Coventry and Warwickshire NHS Trust
2016-2024
Coventry University
2024
University Hospital Coventry
2011-2023
National Health Service
2016-2022
Miscarriage Association
2018-2021
Tommy's
2018-2021
Coventry (United Kingdom)
2012-2021
Aalborg University Hospital
2020
University Hospitals Birmingham NHS Foundation Trust
2020
Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied role of FoxO transcription factors in determining cellular response paclitaxel. Western blotting revealed that a panel nine cancer cell lines expression FoxO1a and FoxO3a correlated with pro-apoptotic target Bim, was associated paclitaxel-induced apoptosis. In MCF-7 cells, were paclitaxel-sensitive, already high basal levels Bim protein increased...
Background Recurrent pregnancy loss (RPL), defined as 3 or more consecutive miscarriages, is widely attributed either to repeated chromosomal instability in the conceptus uterine factors that are poorly defined. We tested hypothesis abnormal cyclic differentiation of endometrial stromal cells (ESCs) into specialized decidual predisposes RPL, based on observation this process may not only be indispensable for placenta formation but also embryo recognition and selection at time implantation....
Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and receptive endometrium. Reproductive success in humans however limited, largely because of the high prevalence chromosomally abnormal preimplantation embryos. Moreover, transient period endometrial receptivity uniquely coincides with differentiation stromal cells (ESCs) into highly specialized decidual cells, which absence pregnancy invariably...
Endometrial cancer is the most common malignancy of lower female reproductive tract. The tumor suppressor FOXO1 downregulated in endometrial compared with normal endometrium but underlying mechanisms are not well understood. Using microRNA (miR) target prediction algorithms, we identified several miRs that potentially bind 3'-untranslated region transcripts. Expression profiling and malignant samples by quantitative real-time PCR Northern blot analysis revealed an inverse correlation between...
Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected may fail to implant although many first breach the endometrial epithelium and embed in decidualizing stroma before being rejected via mechanisms are poorly understood. Here we show developmentally impaired human elicit an endoplasmic stress response decidual cells. A was also evident upon vivo exposure of mouse uteri culture medium conditioned by low-quality embryos. By contrast,...
In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit differentiation into decidual that control embryo implantation. Here we show FOXO1 also causes acute senescence of a subpopulation decidualizing EnSCs an IL-8 dependent manner. Selective depletion or enrichment this...
During the implantation window, endometrium becomes poised to transition a pregnant state, process driven by differentiation of stromal cells into decidual (DC). Perturbations in this process, termed decidualization, leads breakdown feto-maternal interface and miscarriage, but underlying mechanisms are poorly understood. Here, we reconstructed pathway at single-cell level vitro demonstrate that first mount an acute stress response before emerging as DC or senescent (snDC). In absence immune...
Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation stromal which differentiate into specialized decidual cells prior to during pregnancy. Aberrant responsiveness human (HESCs) deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis HESCs did not reveal gross perturbations CpG methylation RPL cultures, although quantitative differences were observed or...
Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into robust matrix that accommodates placenta throughout pregnancy. To gain insights underlying mechanisms, we established and characterized endometrial assembloids, consisting gland-like organoids primary stromal cells. Single-cell transcriptomics revealed decidualized assembloids closely resemble endometrium, harbouring differentiated...
Human endometrial stromal (ES) cells in culture express PRL, a marker of decidualization, response to sustained activation protein kinase A (PKA). Cotreatment with the progestin medroxyprogesterone acetate (MPA) enhanced decidual PRL gene presence elevated intracellular cAMP levels. This synergy became apparent, at and promoter level, after lag period 2 days increased time-dependent manner thereafter. Pretreatment advanced time which between MPA was suggesting that PKA sensitized ES effects...