A5006803120- Reproductive Biology and Fertility
- Assisted Reproductive Technology and Twin Pregnancy
- Ovarian function and disorders
- Prenatal Screening and Diagnostics
- Reproductive Health and Technologies
- Sperm and Testicular Function
- Reproductive System and Pregnancy
- Endometriosis Research and Treatment
- Renal and related cancers
- Reproductive Physiology in Livestock
- Microtubule and mitosis dynamics
- Tissue Engineering and Regenerative Medicine
- DNA Repair Mechanisms
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genetic Syndromes and Imprinting
- Gynecological conditions and treatments
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Risks and Factors
- Genomic variations and chromosomal abnormalities
- Ovarian cancer diagnosis and treatment
- Ethics and Legal Issues in Pediatric Healthcare
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
University of Warwick
2015-2024
University Hospitals Coventry and Warwickshire NHS Trust
2012-2024
Aarhus University Hospital
2020
Sapienza University of Rome
2020
Copenhagen University Hospital
2020
Johns Hopkins University
2020
University of Copenhagen
2020
University Hospital Coventry
1999-2019
Oxford Fertility
2013
Università Cattolica del Sacro Cuore
2009
Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in oocytes from females aged 9 to 43 years report that aneuploidy follows a U-curve. Specific error types show different age dependencies, providing quantitative explanation for the Whole-chromosome nondisjunction events are preferentially associated with increased young girls, whereas centromeric more...
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,...
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 beings are made of ~50 trillion cells which arise from serial mitotic divisions a single cell - the fertilised egg. Remarkably, early human embryo is often chromosomally abnormal, and many mosaic, with karyotype differing one to another. Mosaicism presumably arises chromosome segregation errors during divisions, although these events have never been visualised in living embryos. Here, we establish live imaging using normally embryos an egg-share-to-research programme, as well...
Abstract Decidualizing endometrial stromal cells (EnSC) critically determine the maternal response to an implanting conceptus, triggering either menstruation‐like disposal of low‐fitness embryos or creating environment that promotes further development. However, mechanism couples recognition low‐quality tissue breakdown remains poorly understood. Recently, we demonstrated successful transition cycling endometrium a pregnancy state requires selective elimination pro‐inflammatory senescent...
Telomeres are chromosome ends that control functions related to cell division. Short telomeres proposed underlie infertility, female reproductive ageing and abnormal embryogenesis, but there is little direct evidence on telomere length in gametes embryos. The aim of this study was measure lengths individual human oocytes, spermatozoa, male pronuclei, order compare parental contributions the zygote. Quantitative fluorescence situ hybridization used average pronuclei oocytes fertilized for...
Can the priorities for future research in infertility be identified?The top 10 four areas of male infertility, female and unexplained medically assisted reproduction ethics, access organization care people with fertility problems were identified.Many fundamental questions regarding prevention, management consequences remain unanswered. This is a barrier to improving received by those problems.Potential collated from an initial international survey, systematic review clinical practice...
Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis common cause. We found that loss specific pool the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate SGO2 preserves chromatid cohesion by protecting "cohesin bridge" chromatids. In oocytes, localizes both sub-centromere...
Prenatal oogenesis produces hundreds of thousands oocytes, most which are discarded through apoptosis before birth. Despite this large-scale selection, the survivors do not constitute a perfect population, and factors at cellular level that result in or survival any individual oocyte largely unknown. What then selection criteria determine size quality ovarian reserve women? This review focuses on new data level, human prenatal oogenesis, offering clues about importance timing entry to...
Telomeres are repeated sequences that protect the ends of chromosomes and harbour DNA repair proteins. shorten during each cell division in absence telomerase. When telomere length becomes critically short, senescence occurs. Telomere therefore reflects both cellular ageing capacity for division. We have measured human germinal vesicle (GV) oocytes preimplantation embryos, by quantitative fluorescence situ hybridization (Q-FISH), providing baseline data towards our hypothesis is a marker...
The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed pregnancies. A successful meiosis I (MI) entails separation homologous chromosome pairs co-segregation sister chromatids. For this happen, kinetochores must form attachments spindle kinetochore-fibres emanating from same pole. In mouse budding yeast, remain closely associated with each other during MI, enabling them act as a single unified structure....
Three hypotheses were tested: (i) the distance between first and second polar bodies (PB) may relate to embryo morphology, (ii) that orientation of pronuclei (PN) relative PB (iii) placement a spermatozoon in fixed plane [intracytoplasmic sperm injection (ICSI)] alter PN/PB in-vitro fertilization (IVF). A total 251 two pronuclear (2PN) embryos (124 ICSI, 127 IVF) from 64 patients was studied. Angles measured PN axis nearest (α), furthest (β), (γ). On day 2, morphological grades recorded. γ...
Blastocysts from 198 patients were frozen using glycerol as cryoprotectant. No difference in the post-thaw survival of blastocysts or implantation rates was found between 177 (122 transfers) with all surplus embryos cultured to before freezing and 20 (12 whose considered unsuitable for during cleavage then blastocysts. Nineteen pregnancies achieved, which six aborted. Pre-freezing morphology similar groups 1 2 did not relate their after cryopreservation. A significantly lower proportion...
Abstract Background The vast majority of oocytes formed in the fetal ovary do not survive beyond birth. Possible reasons for their loss include elimination non-viable genetic constitutions arising through meiosis, however, precise relationship between meiotic stages and prenatal apoptosis remains elusive. We studied mouse neonatal ovaries, 14.5–21 days post coitum, to examine oocyte development programmed cell death during prophase I. Results Microspreads ovarian cells underwent...
Oocyte competence for maturation and embryogenesis is associated with diameter in many mammals. We aimed to test whether this relationship exists humans quantify its impact upon vitro (IVM).We used computer-assisted image analysis daily measure average diameter, zona thickness other parameters oocytes. Immature oocytes originated from unstimulated patients polycystic ovaries, stimulated undergoing intracytoplasmic sperm injection (ICSI). Some were cultured meiosis activating sterol (FF-MAS)....
An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach determining what can be deduced about couple's future chances of pregnancy from the number menstrual cycles over which they been trying conceive. The starting point that fertility inherently uncertain. uncertainty modelled as probability distribution for chance conceiving...
Human reproduction is inherently inefficient and 1 in 6 people worldwide suffer infertility. In vitro fertilisation (IVF) can help some couples conceive, but only ~30% of cycles are successful. One factor affecting IVF efficacy mitotic-origin (mosaic) aneuploidy which embryos contain a mixture cells with different numbers chromosomes. We previously showed that chromosome segregation error phenotypes frequent the first mitotic division human embryo. However, cause these errors impact on...