About

Blanche Capel is the James B. Duke Distinguished Professor of Cell Biology at Duke University School of Medicine. She is also a Professor of Cell Biology, a member of the Duke Cancer Institute, and an affiliate of the Duke Regeneration Center. Her research focuses on cell and molecular biology, with involvement in programs such as the Program in Cell and Molecular Biology, Developmental & Stem Cell Biology Program, and the University Program in Genetics and Genomics. She is based at 307 Research Drive, Nanaline Bldg Room 452, Durham, NC 27710.

Research topics

• Biology
• Genetics
• Cell biology
• Molecular biology
• Biochemistry
• Chemistry

Selected publications

• Glycogen and lactate metabolism in mouse fetal Sertoli cells sustain the germ line

  Cell Reports · 2026-03-01

  articleOpen accessSenior author

  Metabolites are key regulators of cell fate decisions, chromatin remodeling, and lineage commitment. While genetic pathways governing testis differentiation are well studied, the role of metabolism remains poorly understood. In this study, we investigate the transient, male-specific accumulation of glycogen in supporting cells of the fetal testis in mice, between embryonic days 11.5 and 13.5. Blocking glycogen metabolism/accumulation in vivo and in vitro is dispensable for Sertoli cell differentiation. However, its disruption leads to reduced lactate production and reduced germ cell number in the testis. Inhibiting lactate transport reveals a critical metabolic coupling between Sertoli and germ cells during early testis development. Surprisingly, external lactate or glucose supplementation fails to rescue the germ cell phenotype. These findings suggest that glycogen accumulation supports a critical developmental window in which both Sertoli and germ cells are metabolically constrained and unable to rely on external carbon sources.

  PublisherDOI

• Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs

  Nature Structural & Molecular Biology · 2026-02-24 · 1 citations

  articleOpen accessCorresponding

  Mammalian sex is determined by opposing networks of ovarian and testicular genes that are well characterized; however, its epigenetic regulation is still largely unknown. Here we explore the 3D chromatin landscape of sex determination in vivo by profiling fluorescence-activated cell-sorted embryonic mouse gonadal populations in both sexes before and after sex determination. Through conventional Hi-C analyses, we show that chromatin structures, particularly topologically associating domains, remain largely unchanged during sex determination, suggesting a preformed configuration. We further integrate Hi-C data with ChIP-seq experiments using METALoci, a spatial autocorrelation analysis that identifies three-dimensional (3D) regulatory hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination, affecting the 3D regulatory hubs of hundreds of genes that display time-specific and sex-specific expression. By combining predictive approaches and validations in transgenic mice, we identify a 3D regulatory hub for the protesticular gene Fgf9. The deletion of this gonad-specific hub allows mutant mice to survive through development, overcoming lung lethality associated with Fgf9 loss of function while exhibiting male-to-female sex reversal. Through the reconstruction of gene regulatory networks, we identify a function for Meis genes, which act redundantly to specify sexual identity during ovarian and testicular development. Our results underscore the dynamic role of the 3D genome during sex determination, highlighting the potential of epigenomic approaches to uncover regulators of developmental processes.

  PublisherDOI

• Platelet-derived growth factor receptor alpha regulates fetal testis differentiation via an ERK–CREB axis

  Proceedings of the National Academy of Sciences · 2026-01-21

  articleOpen access

  Platelet-derived growth factor receptor alpha ( Pdgfra ) plays a crucial role in mesenchymal cell differentiation, but the molecular signaling involved in this process remains unclear, particularly within the fetal testis. Here, we use XY Pdgfra -null gonads to investigate the molecular mechanisms underlying testicular organogenesis, focusing on the formation of testicular architecture and the differentiation of fetal Leydig cells (FLCs), the steroidogenic lineage arising from mesenchymal precursors within the testicular interstitial compartment. The extracellular signal-regulated kinase (ERK) pathway, a well-known mitogen-activated signaling pathway, was significantly inhibited in XY Pdgfra -null gonads, suggesting that ERK signaling is activated downstream of PDGFRA. Using ex vivo whole-organ culture, small interfering RNA cell culture methods, transwell assays, and a genetic mouse model to disrupt ERK signaling in gonadal cells, we found that the ERK pathway promotes testis cord formation via early growth response 1 -mediated cell migration and regulates the expression of steroidogenic enzymes in FLCs via activating the transcription factor cAMP responsive element binding protein 1. These findings highlight the significance of the PDGFRA signaling network in fetal testis organogenesis, thus providing insights into mesenchymal cell differentiation and the etiology of congenital disorders related to gonadal development.

  PublisherOA PDFDOI

• Flexibility of cell fates and functions across sex determination systems revealed by comparative single-cell analyses

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-30

  articleOpen access

  ABSTRACT Sex determination in vertebrates can be initiated by a wide range of genetic or environmental triggers. Yet, the degree to which gonadal cell types and genetic programs are conserved remains unresolved. Here we employed single-cell transcriptomics to characterize the temperature-dependent sex determination (TSD) program in gonads from the turtle species Trachemys scripta. Comparative analyses against species with genetic sex determination, like mouse (XY) and chicken (ZW), revealed a marked divergence in cell type repertoires and functions during vertebrate evolution. Unlike mammals, fetal Leydig cells are absent from the early gonads of T. scripta , where the supporting lineage expresses genes required for androgen synthesis. Evolutionary reconstructions show that this lineage derives from a Pax2 -positive mesenchymal population, suggesting an ancestral condition in Archelosauria that differs from the primarily coelomic epithelium origin in the mammalian clade. Transcriptional dynamics and co-expression analyses revealed the recruitment of lineage-specific transcription factors, including Twist1 or Runx1 , into the genetic programs of vertebrate clades. Our findings reveal extensive plasticity of the cellular and genetic mechanisms of vertebrate sex determination and suggest that this flexibility is a key feature of gonadal evolution.

  PublisherDOI

• Author response: Rediscovering the rete ovarii, a secreting auxiliary structure to the ovary

  2025-03-19

  peer-reviewOpen accessSenior author
  PublisherDOI

• Rediscovering the rete ovarii, a secreting auxiliary structure to the ovary

  eLife · 2025-03-19 · 3 citations

  articleOpen accessSenior author

  The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the mouse ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow toward the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherDOI

• Granulosa cell death is a significant contributor to DNA-damaging chemotherapy-induced ovarian insufficiency

  Biology of Reproduction · 2025-04-03 · 7 citations

  articleOpen accessSenior author

  Typically, DNA-damaging chemotherapy (CTx) regimens have a gonadotoxic effect and cause premature ovarian insufficiency (POI), characterized by infertility and estrogen deficiency. However, whether loss of granulosa cells killed directly by CTx contributes significantly to POI has not been determined. To address this issue, we used a previously established mouse model of CTx-induced POI. The alkylating drugs Busulfan (8.75 mg/kg) and Cyclophosphamide (100 mg/kg) were administered to 8-week-old FVB female mice by intraperitoneal (IP) injection three times at 48-h intervals, after which ovarian tissues were harvested and examined by immunofluorescence. The number of primordial follicles was significantly reduced at day (d)6, whereas the number of growing follicles was relatively unchanged. CTx led to DNA double strand breaks in both oocytes and granulosa cells based on the presence of γH2AX foci. However, markers of apoptosis predominantly labeled granulosa cells in growing follicles. We next examined the effect of inhibiting apoptosis in growing granulosa cells by generating Bak-/-Baxfx/fx; Cyp19a1Cre transgenic mice. On d10 after the first CTx, Bak-/-Baxfx/fx; Cyp19a1Cre ovaries had fewer apoptotic granulosa cells and more surviving follicles than controls. Furthermore, Bak-/-Baxfx/fx; Cyp19a1Cre mice showed better fertility than controls after CTx. Our data suggest that granulosa cell death is a significant contributor to follicle depletion and fertility loss after Cyclophosphamide and Busulfan.

  PublisherOA PDFDOI

• Author response: Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

  2025-02-12

  peer-reviewOpen accessSenior author

  The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherDOI

• KDM6B is a conserved activator at the top of the male sex determination pathway

  Development · 2025-05-23 · 3 citations

  articleSenior author

  In mammals, commitment to the testis fate is controlled by the gene Sry on the Y chromosome; however, how Sry is regulated is not well understood. In the red-eared slider turtle, Dmrt1 acts as the primary activator of the testis pathway. Removal of the repressive histone modification H3K27me3 from Dmrt1 by the histone demethylase KDM6B is required for its activation. We hypothesized that a similar de-repression mechanism is used in mammals to activate the testis pathway. Using a mouse knockout model for Kdm6b, we found that loss of Kdm6b leads to a delay in Sry activation and the development of an ovotestis. These results implicate KDM6B as a conserved regulator at the top of the sex determination cascade in both reptiles and mammals.

  PublisherDOI

• Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

  eLife · 2025-02-12 · 1 citations

  preprintOpen accessSenior author

  Abstract The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherOA PDFDOI

Recent grants

• Identification of a Genetic Pathway Linking Temperature with Epigenetic Control of Gonad Determination in T. scripta

  NSF · $900k · 2019–2024

• NIH Grant R01HL063054

  NIH · $1.7M · 2008

• NIH Grant R01GM056757

  NIH · $527k · 2000

• Opposing Pathways in Mammalian Sex Determination

  NIH · $305k · 1998–2011

• Defining Mechanisms of Ovarian Rescue

  NIH · $1.6M · 2017–2022

Frequent coauthors

• Jennifer McKey

  University of Colorado Anschutz Medical Campus

  86 shared

• Tony DeFalco

  Cincinnati Children's Hospital Medical Center

  83 shared

• Corey Bunce

  81 shared

• Danielle M. Maatouk

  66 shared

• Jonah Cool

  Chan Zuckerberg Initiative (United States)

  56 shared

• Humphrey Hung‐Chang Yao

  National Institute of Environmental Health Sciences

  55 shared

• Lindsey Mork

  University of Southern California

  55 shared

• Leo DiNapoli

  Duke University

  53 shared

Education

• Ph.D., Genetics

  University of Pennsylvania

  1989