About

Francisco J. Diaz is an Associate Professor of Reproductive Biology at the Pennsylvania State University Department of Animal Science. His research focuses on reproductive biology, contributing to the understanding of animal reproductive processes. As a faculty member, he is involved in advancing the sciences related to animal reproduction, supporting education and research within the department.

Research topics

• Genetics
• Biology
• Internal medicine
• Cell biology
• Chemistry
• Endocrinology
• Andrology
• Neuroscience
• Ecology

Selected publications

• Zinc deficiency in bovine mural granulosa cells results in hippo pathway-mediated apoptosis

  Biology of Reproduction · 2025-10-02 · 1 citations

  articleSenior author

  Zinc is essential for the proper functioning of a variety of cells and tissues. Due to the limited understanding of the role of zinc in the bovine ovary, our objective was to investigate the role of zinc in bovine mural granulosa cell (mGC) viability and identify cell signaling pathways regulated by zinc in this cell type. Key indicators of cell behavior were measured after cultured bovine mGCs were incubated with increasing levels of a zinc chelator, TPEN. Cell viability decreased in a dose dependent manner, with a 91% loss of cell viability seen at 10 μM TPEN (p = 1.02 × 10-9), which corresponded to a 49% increase in caspase 3/7 activity (p = 0.006) and an upregulation of p-YAP at Ser127 (p = 0.006). TRULI, a potent LATS1/2 inhibitor, in combination with TPEN treatments, partially rescued the decrease in cell viability seen at 3.5 μM TPEN (p = 2.54 × 10-7) and the increase in caspase 3/7 activity seen at 10 μM TPEN (p = 0.0003). Surprisingly, TPEN treatment for 6 h showed a dose dependent increase in relative fold change in expression of the known YAP gene targets, CCN1 (p = 3.85 × 10-10) and CCN2 (p = 1.95 × 10-7). While the mechanism by which increased Hippo activation mediates TPEN-stimulated apoptosis is still unknown, these results demonstrate that zinc is an essential micronutrient for bovine mGC viability, and that zinc deficiency promotes Hippo signaling leading to increased apoptosis in bovine mGCs.

  PublisherDOI

• Exploring the decentralized science ecosystem: insights on organizational structures, technologies, and funding

  Frontiers in Blockchain · 2025-02-28 · 3 citations

  articleOpen access1st authorCorresponding

  Introduction The scientific community is increasingly interested in leveraging decentralized technologies to address systemic challenges such as the reputation economy, the monopolization of academic publishing, and the replication crisis. This study presents an analysis of the Decentralized Science (DeSci) landscape in 2023, focusing on organizational structures, technological foundations, and funding mechanisms of DeSci organizations. Methods A 16-question survey was distributed to DeSci organizations between December 2023 and April 2024, and responses from 49 projects were analyzed using quantitative and qualitative methods. Results Results highlight the prominent role of Ethereum as the dominant blockchain platform in DeSci, the varied applications of blockchain in scientific processes, and a significant emphasis on community building and infrastructure development. Funding sources within the ecosystem are moving towards partnerships with more traditional organizations, including academia. However, most projects lack DAO features for governance. It remains uncertain whether they will adopt more DAO-like structures in the future or deploy a different organizational model. Discussion Our findings offer a comprehensive overview of the progress and challenges facing the DeSci ecosystem, including slow project progression due to leadership issues and limited funding for most DeSci projects. By identifying key patterns and areas for improvement, this study contributes to a deeper understanding of the factors driving success and sustainability in DeSci.

  PublisherOA PDFDOI

• DTPA disrupts development of preantral ovarian follicles in vitro

  Reproduction and Fertility · 2025-09-30 · 2 citations

  articleOpen accessSenior author

  Abstract: Dietary zinc deficiency disrupts fertility in vivo by impairing oocyte and embryo development near ovulation. Acute treatment of newborn ovaries with a strong intracellular chelator (TPEN), which preferentially binds zinc, disrupts follicular development. However, the chronic effects of transition metal chelation on preantral follicle development are not known. In this study, the effect of the extracellular transition metal chelator, diethylenetriaminepentaacetic acid (DTPA), was used to examine more prolonged effects on preantral follicle development. Preantral granulosa cell-oocyte complexes from 14-day-old mice were cultured under control, chelated (DTPA), or rescue (DTPA + ZnSO4) conditions for up to 10 days. Preantral follicles cultured in DTPA alone showed impaired growth, disrupted nucleolar morphology, and impaired meiotic progression. The granulosa cells in DTPA-treated follicles underwent apoptosis at a higher rate than controls, had fewer physical connections to the oocyte, and reduced activation of pSMAD2 signaling. Moreover, Lhcgr and Ar transcripts were higher in cumulus cells, and Figla was lower in oocytes from DTPA-treated follicles. These data support a role for transition metals in general, and zinc in particular, in proper development of preantral ovarian follicles. The loss of somatic support cells explains some or all of the growth and developmental deficits seen in the DTPA-treated oocytes. DTPA preferentially binds zinc. Therefore, these results support growing evidence that a proper supply of transition metals, including zinc, is essential for optimal ovarian function. Lay summary: The roles the mineral zinc plays in the ovary are not yet clear. The present study used follicles from mouse ovaries that were grown in the lab for up to 10 days. Follicles are round structures that contain a large egg cell at the center, surrounded by smaller cells called granulosa cells. Follicles were either grown with adequate zinc or insufficient zinc levels. The findings show that follicles require sufficient zinc to form connections between the egg and granulosa cells, which are essential for growth of both the egg and the granulosa cells. When there is insufficient zinc, loss of these connections leads to more granulosa cells dying and smaller follicles. These results show that zinc is important for growth of ovarian follicles, which could be important for treating infertility by supplying adequate levels of zinc in the diet.

  PublisherDOI

• Exploring the Decentralized Science Ecosystem: Insights on Organizational Structures, Technologies, and Funding

  2024-11-06

  preprintOpen access1st authorCorresponding

  The scientific community is increasingly interested in leveraging decentralized technologies to address systemic challenges such as the reputation economy, the monopolization of academic publishing, and the replication crisis. This study presents a comprehensive analysis of the Decentralized Science (DeSci) landscape in 2023, focusing on organizational structures, technological foundations, and funding mechanisms of DeSci projects and organizations. A 16-question survey was distributed to DeSci projects between December 2023 and April 2024, and responses from 49 projects were analyzed using quantitative and qualitative methods. Results highlight the prominent role of Ethereum as the dominant blockchain platform in DeSci, the varied applications of blockchain in scientific processes, and a significant emphasis on community building and infrastructure development. Funding sources within the ecosystem are moving towards partnerships with more traditional organizations, including academia. However, most projects lack DAO features for governance. It remains uncertain whether they will adopt more DAO-like structures in the future or deploy a different organizational model. Our findings offer a comprehensive overview of the progress and challenges facing the DeSci ecosystem, including slow project progression due to leadership issues and limited funding for most DeSci projects. By identifying key patterns and areas for improvement, this study contributes to a deeper understanding of the factors driving success and sustainability in DeSci.

  PublisherOA PDFDOI

• Evaluation of the Safety and Immunogenicity of a Multiple Epitope Polypeptide from Canine Distemper Virus (CDV) in Mice

  Vaccines · 2024-10-04 · 5 citations

  articleOpen access

  BACKGROUND: is the etiological agent of a highly contagious disease that affects diverse domestic and wild animals. Vaccination is considered the most suitable strategy for controlling CDV dissemination, transmission, and distemper disease. However, the emergence of new CDV strains has led to the need to update the current vaccine strategies employed to prevent CDV infection in domestic and wild animals. Currently, there is a lack of effective alternatives for wild animals. Diverse computational tools, especially peptide-based therapies, enable the development of new universal vaccines. OBJECTIVE: The aim of this study was to evaluate the safety and humoral and cellular immune response of a new generation of vaccines based on CDV peptides as single-peptide mixtures or multiepitope CDV polypeptides in mice. METHODS: Twenty-four BALB/c mice were subjected to a three-dose regimen for 28 days. Seroconversion was evaluated via ELISA, and cellular immune responses were evaluated via flow cytometry through activation-induced markers (AIMs). RESULTS: Compared with the placebo, the peptide mixture and multiepitope CDV polypeptide were safe, and seroconversion was statistically significant in the multiepitope CDV polypeptide and commercial vaccine (CV) groups. The numbers of antigen-specific CD4+CD134+ and IFN-γ+ T cells, CD8+ T cells and TNF-α- and IL-6-producing cells were greater in the mice immunized with the multiepitope CDV polypeptide than in the control mice. CONCLUSION: This combined approach represents a potential step forward in developing new immunization candidates or enhancing current commercial vaccines to control CDV disease in domestic dogs and wild animals.

  PublisherOA PDFDOI

• Synergistic enhancement of the mouse Pramex1 and Pramel1 in repressing retinoic acid (RA) signaling during gametogenesis

  Cell & Bioscience · 2024-02-23 · 2 citations

  articleOpen access

  BACKGROUND: PRAME constitutes one of the largest multi-copy gene families in Eutherians, encoding cancer-testis antigens (CTAs) with leucine-rich repeats (LRR) domains, highly expressed in cancer cells and gametogenic germ cells. This study aims to elucidate genetic interactions between two members, Pramex1 and Pramel1, in the mouse Prame family during gametogenesis using a gene knockout approach. RESULT: Single-gene knockout (sKO) of either Pramex1 or Pramel1 resulted in approximately 7% of abnormal seminiferous tubules, characterized by a Sertoli-cell only (SCO) phenotype, impacting sperm count and fecundity significantly. Remarkably, sKO female mice displayed normal reproductive functions. In contrast, Pramex1/Pramel1 double knockout (dKO) mice exhibited reduced fecundity in both sexes. In dKO females, ovarian primary follicle count decreased by 50% compared to sKO and WT mice, correlating with a 50% fecundity decrease. This suggested compensatory roles during oogenesis in Pramex1 or Pramel1 sKO females. Conversely, dKO males showed an 18% frequency of SCO tubules, increased apoptotic germ cells, and decreased undifferentiated spermatogonia compared to sKO and WT testes. Western blot analysis with PRAMEX1- or PRAMEL1-specific antibodies on sKO testes revealed compensatory upregulation of each protein (30-50%) in response to the other gene's deletion. Double KO males exhibited more severe defects in sperm count and litter size, surpassing Pramex1 and Pramel1 sKO accumulative effects, indicating a synergistic enhancement interaction during spermatogenesis. Additional experiments administering trans-retinoic acid (RA) and its inhibitor (WIN18,446) in sKO, dKO, and WT mice suggested that PRAMEX1 and PRAMEL1 synergistically repress the RA signaling pathway during spermatogenesis. CONCLUSION: Data from sKO and dKO mice unveil a synergistic interaction via the RA signaling pathway between Pramex1 and Pramel1 genes during gametogenesis. This discovery sets the stage for investigating interactions among other members within the Prame family, advancing our understanding of multi-copy gene families involved in germ cell formation and function.

  PublisherOA PDFDOI

• Ovarian Production of Estradiol: The Two-Cell, Two-Gonadotropin Model

  Elsevier eBooks · 2024-07-14

  book-chapter1st authorCorresponding
  PublisherDOI

• Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study

  Journal of the American Nutrition Association · 2022-03-24 · 6 citations

  articleOpen access

  To evaluate variations in micronutrient biomarker concentrations and deficiencies across the menstrual cycle in a cohort of healthy women. = 45). Data collection occurred at the early follicular phase, the late follicular phase, and the midluteal phase. Fasting blood samples were collected to measure micronutrient biomarkers. = 0.025). Our study suggests that while many micronutrient concentrations are relatively constant across the menstrual cycle in healthy women, zinc and magnesium decline, and the prevalence of magnesium deficiency increases. Supplemental data for this article is available online at.

  PublisherOA PDFDOI

• Role of the bovine PRAMEY protein in sperm function during in vitro fertilization (IVF)

  Cell and Tissue Research · 2022-12-17 · 4 citations

  article
  PublisherDOI

• A reconfigurable microfluidic building block platform for high-throughput nonhormonal contraceptive screening

  Lab on a Chip · 2022-01-01 · 6 citations

  articleCorresponding

  , branching microchannels, chemical gradient generators, pumpless flow controllers, and emulsion generators) or an open interface. The middle layer incorporates a multiwell array with embedded membrane filters for live cell culture, medium exchange, enzymatic cumulus cell removal, washing, and fluorescence staining. The bottom layer is also reconfigurable for waste collection, oocyte culture, plate reader measurement, and high-resolution microscopy. We demonstrate an 8 by 16 (128 wells) system for performing the cumulus-oocyte complex (COC) expansion and oocyte maturation assays for screening nonhormonal contraceptives. The microfluidic building block platform is scalable and can be reconfigured for a variety of drug screening applications in the future.

  PublisherDOI

Recent grants

• RIG: Analysis of ING proteins during avian follicular development

  NSF · $175k · 2009–2012

• NIH Grant R03HD057283

  NIH · $147k · 2014

Frequent coauthors

• S. Guerchicoff

  University of Bern

  16 shared

• Saúl Drajer

  16 shared

• H. J. Dengler

  16 shared

• H. Kunik

  Federal Government of Germany

  16 shared

• F. Gross

  University of Zurich

  16 shared

• M Olle

  MVZ - Kurfürstendamm

  16 shared

• Barry G. Woodcock

  16 shared

• Larry J. Siegel

  16 shared

Education

• B.S.

  University of Vermont

  1994

• M.S.

  University of Wisconsin-Madison

  1999

• Ph.D.

  University of Wisconsin-Madison

  2003

• Other

  The Jackson Laboratory

  2007