About

Robin Skory, MD, PhD, is an Assistant Professor of Obstetrics and Gynecology at the University of Pennsylvania Perelman School of Medicine. He serves as an Attending in Gynecology at Penn Presbyterian Medical Center and specializes in Reproductive Endocrinology and Infertility at Pennsylvania Hospital, as well as in Reproductive Endocrinology and Infertility at the Hospital of the University of Pennsylvania. Dr. Skory's research focuses on live-imaging, embryo development, fertilization, folliculogenesis, and related reproductive processes. His work involves capturing real-time events of fertilization in mouse and human models, studying nuclear DNA shedding during blastocyst expansion, and exploring mechanisms of cell fate determination in preimplantation embryos. He has contributed to advancing imaging technologies and understanding the cellular and molecular mechanisms underlying early human development.

Research topics

• Biology
• Cell biology
• Andrology
• Medicine
• Genetics

Selected publications

• Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo

  Science · 2025-05-22 · 16 citations

  articleOpen access

  Following fertilization, the preimplantation embryo undergoes successive rounds of cell division and must accurately propagate the genetic material to ensure successful development. However, early mammalian embryos lack efficient spindle assembly mechanisms, and it remains unclear how error-free chromosome segregation is achieved. In this work, we imaged early mouse embryos and identified a network of nuclear actin cables that organize prophase chromosomes at the nuclear periphery. Following nuclear envelope breakdown, the network contracts and gathers chromosomes toward the cell center. Network contraction was driven by filament disassembly in a myosin II-independent manner. Additionally, we identified a network of branched actin filaments that attenuates metaphase spindle elongation. We also visualized nuclear actin in human embryos, suggesting a conserved role for actin in ensuring mitotic fidelity during early mammalian development.

  PublisherDOI

• Capturing aberrant cell behaviors producing defects in human embryos via live imaging

  Science Advances · 2025-11-19 · 4 citations

  articleOpen access

  The generation of human embryos in vitro has revolutionized reproductive medicine, and also made it possible to study fundamental aspects of early human development. However, human preimplantation embryos often display an array of morphological defects associated with poor development and implantation. Here, we used live-embryo imaging and computational analysis to capture how these defects can be produced in real time. We record various forms of mitotic errors including lagging chromosomes producing micronuclei, multipolar spindles causing abnormal chromosome organization recapitulated by daughter cells, and uncontrolled scattering of condensed chromosomes. In addition, we capture abnormal cleavage furrow dynamics during cytokinesis producing binucleated and enucleated cells. Finally, we find cells with disrupted mitotic progression ultimately leading to blebbing and fragmentation. Thus, these results document specific aberrant cell behaviors producing morphological defects in real time, and indicate that errors during mitosis and cytokinesis represent a major cause of developmental failures in human embryos.

  PublisherDOI

• LIVE-IMAGING FERTILIZATION IN MOUSE AND HUMAN

  Fertility and Sterility · 2025-12-01

  article1st authorCorresponding
  PublisherDOI

• Revisiting trophectoderm-inner cell mass lineage segregation in the mammalian preimplantation embryo

  Human Reproduction · 2024-06-13 · 7 citations

  reviewOpen access1st authorCorresponding

  In the first days of life, cells of the mammalian embryo segregate into two distinct lineages, trophectoderm and inner cell mass. Unlike nonmammalian species, mammalian development does not proceed from predetermined factors in the oocyte. Rather, asymmetries arise de novo in the early embryo incorporating cues from cell position, contractility, polarity, and cell-cell contacts. Molecular heterogeneities, including transcripts and non-coding RNAs, have now been characterized as early as the 2-cell stage. However, it's debated whether these early heterogeneities bias cells toward one fate or the other or whether lineage identity arises stochastically at the 16-cell stage. This review summarizes what is known about early blastomere asymmetries and our understanding of lineage allocation in the context of historical models. Preimplantation development is reviewed coupled with what is known about changes in morphology, contractility, and transcription factor networks. The addition of single-cell atlases of human embryos has begun to reveal key differences between human and mouse, including the timing of events and core transcription factors. Furthermore, the recent generation of blastoid models will provide valuable tools to test and understand fate determinants. Lastly, new techniques are reviewed, which may better synthesize existing knowledge with emerging data sets and reconcile models with the regulative capacity unique to the mammalian embryo.

  PublisherOA PDFDOI

• O-172 Live imaging reveals key events in preimplantation embryo development

  Human Reproduction · 2024-07-01

  article1st authorCorresponding

  Abstract Preimplantation development encompasses the zygote to blastocyst stages, occurring in vivo within the Fallopian tube and in vitro within embryology labs worldwide. During these first five days of life, several key morphologic changes take place facilitating cell fate specification and resulting in blastocyst assembly containing ICM and trophectoderm lineages. These include cell polarization, embryo compaction and inner-outer segregation, which transform the collection of blastomeres into a morula. Subsequently, the blastocoel cavity forms and expands followed by hatching from the zona pellucida prior to implantation. This ability to self-organize has enabled live imaging of these events within intact embryos. Moreover, this has revealed the dynamics of early mitoses, nuclear morphology and cytoskeletal changes driving early development. Although a great deal has been learned in the mouse, events in the human embryo remain relatively unknown. Recent achievements in stem cell-based embryoid models and non-invasive live imaging now poise researchers to make significant advancements unveiling human embryo development. Furthermore, a comprehensive understanding of human embryogenesis is essential to improving IVF efficiency and outcomes. Preimplantation development in mouse and human will be reviewed with a focus on recent discoveries made possible by live imaging.

  PublisherDOI

• ONE-STEP WARMING: OPTIMIZES WORKFLOW AND EFFICIENCY IN THE IVF LABORATORY WITHOUT COMPROMISING OUTCOMES

  Fertility and Sterility · 2024-10-01

  article
  PublisherDOI

• Neurulation of the cynomolgus monkey embryo achieved from 3D blastocyst culture

  Cell · 2023-05-01 · 54 citations

  letterOpen access

  Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely unknown due to prohibitions on human embryo research and limitations of available model systems. Here, we establish a three-dimensional (3D) prolonged in vitro culture (pIVC) system supporting cynomolgus monkey embryo development from 7 to 25 days post-fertilization. Through single-cell multi-omics analyses, we demonstrate that pIVC embryos form three germ layers, including primordial germ cells, and establish proper DNA methylation and chromatin accessibility through advanced gastrulation stages. In addition, pIVC embryo immunofluorescence confirms neural crest formation, NT closure, and neural progenitor regionalization. Finally, we demonstrate that the transcriptional profiles and morphogenetics of pIVC embryos resemble key features of similarly staged in vivo cynomolgus and human embryos. This work therefore describes a system to study non-human primate embryogenesis through advanced gastrulation and early neurulation.

  PublisherOA PDFDOI

• Human embryo live imaging reveals nuclear DNA shedding during blastocyst expansion and biopsy

  Cell · 2023-07-01 · 68 citations

  articleOpen access
  PublisherOA PDFDOI

• Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids

  Cell · 2023-07-20 · 130 citations

  articleOpen access
  PublisherOA PDFDOI

• Human Embryo Live Imaging Reveals Nuclear DNA Shedding During Blastocyst Expansion and Biopsy

  Obstetrical & Gynecological Survey · 2023-10-01 · 1 citations

  article

  ABSTRACT The proportion of babies born from in vitro fertilization (IVF) is rising at an exponential rate, highlighting the importance that we have a comprehensive understanding of human preimplantation development and determinants of embryo quality. The early divisions of the embryo after fertilization but before implantation and resulting mitotic errors have been studied primarily in the mouse embryo; however, thus far we have lacked the technology to characterize these critical steps in humans. Establishing an approach that can bypass genetic manipulation and microinjections of DNA or mRNA into human embryos would allow us to better uncover the processes patterning preimplantation human development. This study aimed to evaluate human blastocyst preimplantation development with noninvasive imaging using membrane permeable fluorescent dyes. First, the dyes SPY650-DNA, which labels genomic DNA, and SPY555-actin, which labels F-actin, were validated in the mouse embryo where they produced high contrast labelling with similar results to microinjection of fluorescent mRNAs and produced offspring at a similar rate to nondyed control embryos. Live imaging data using these dyes enabled 3-dimensional scans of the embryo at 5- to 10-minute intervals of the following central events during preimplantation development: the main phases of mitosis, visualizing the major changes in cell shape that characterize embryo compaction at the 8-cell stage, detecting cell polarization at the 8-cell stage, establishing apical F-actin rings at the 16-cell stage, tracking the expansion and zippering of F-actin rings, detecting the first internalized cells within the 16-cell embryo, and visualizing blastocyst expansion and hatching from the zona pellucida. Cleavage-stage human IVF embryos were then studied using the fluorescent dyes to track early cellular and morphogenetic processes. Early cell-cycle dynamics and mitotic stages revealed that the duration of human mitosis is similar to that of mice, but interphase is 27% ± 4% longer in humans (16.1 ± 0.9 vs 12.7 ± 0.4 hours; P < 0.01). Using live imaging, compaction dynamics such as increased cell-cell contact and angle between apical membranes with a decrease in cell sphericity were observed beginning at the 12-cell stage and differed significantly from development in mice. In comparison to mice, human compaction was found to be more asynchronous and did not have clear links to apical polarization or inner-outer segregation. Next, chromosomal segregation was analyzed to determine if this approach allowed detection of segregation errors in the human embryo leading to aneuploidy. Lagging chromosomes detected in human embryos using SPY-DNA appeared morphologically similar to those found in mouse embryos and had similar segregation dynamics. During blastocyst expansion, a subset of trophectoderm cell nuclei forms protruding bud-like that is shed into cytoplasm producing cytoplasmic DNA structures (cytDNA), suggesting an additional process of DNA loss different from chromosome segregation errors during mitosis. A perinuclear keratin network developing at the early cavitation stage appears to protect from formation of cytDNA structures, and the mechanical stress of blastocyst expansion appeared to disrupt the keratin network in certain cells, increasing DNA shedding. Next, trophectoderm biopsy was conducted in mouse, and human embryos to determine if the mechanical stress would increase DNA shedding. Biopsy of human blastocysts resulted in a significant increase in nuclear budding (6.0% vs 0.70%; P = 0.0022), suggesting a link between mechanical stress and DNA shedding. This study demonstrates the use of fluorescent dyes and live imaging in characterization of key cellular and morphogenetic processes patterning the preimplantation human embryo and describes a process of DNA shedding in response to mechanical stressors that warrants future research.

  PublisherDOI

Frequent coauthors

• Nicolas Plachta

  University of Pennsylvania

  17 shared

• Adam A. Moverley

  University of Pennsylvania

  16 shared

• Carlos Simón

  15 shared

• Piotr Tetlak

  California Institute for Regenerative Medicine

  14 shared

• Oz Pomp

  California Institute for Regenerative Medicine

  14 shared

• Stéphanie Bissière

  University of Pennsylvania

  14 shared

• Ana Domingo-Muelas

  Universitat de València

  12 shared

• Blake Hernandez

  California Institute for Regenerative Medicine

  10 shared

Education

• Fellow, Reproductive Endocrinology and Infertility, Obstetrics and Gynecology

  University of Pennsylvania

  2022

• Resident, Obstetrics and Gynecology

  University of California, San Francisco

  2019

• MD

  Northwestern University Feinberg School of Medicine

  2015

• PhD, Biological Sciences

  Northwestern University - Chicago

  2013