About

Juanmahel Davila is an Assistant Professor of Anatomy and Reproductive Biology at the College of Veterinary Medicine, University of Illinois at Urbana-Champaign. He serves as the Head of the Anatomy Section in Comparative Biosciences and is also the Assistant Director of Graduate Studies within the same department. His educational background includes a BS from Universidad de Puerto Rico en Bayamón, a PhD from the University of Illinois at Urbana-Champaign, and a Postdoctoral fellowship at the University of Illinois at Urbana-Champaign. His research interests encompass basic sciences such as cell and molecular biology, reproductive biology, toxicology, cell signaling, physiology, and developmental origins of adult disease. He teaches courses including Clinical Practice I, Structure and Function I, II, and III, Veterinary Medical Spanish, Systems Toxicology, and a seminar in Comparative Biosciences. Dr. Davila is affiliated with professional organizations such as the American Association of Veterinary Anatomists, Society for the Study of Reproduction, and Society of Toxicology.

Research topics

• Biology
• Genetics
• Internal medicine
• Endocrinology
• Physiology
• Medicine
• Chemistry
• Andrology
• Toxicology

Selected publications

• Progesterone Signaling in the Endometrium

  Elsevier eBooks · 2024-07-14

  book-chapter1st authorCorresponding
  PublisherDOI

• Genetic Mouse Models for Female Reproductive Toxicology Studies

  Elsevier eBooks · 2024

  1st authorCorresponding
  • Biology
  • Toxicology
  • Genetics
  PublisherDOI

• Exposure to di-isononyl phthalate during early pregnancy disrupts decidual angiogenesis and placental development in mice

  Reproductive Toxicology · 2023 · 9 citations

  • Endocrinology
  • Biology
  • Andrology
  PublisherOA PDFDOI

• Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation

  Scientific Reports · 2021 · 17 citations

  • Endocrinology
  • Internal medicine
  • Biology

  Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly used for its plasticizing capabilities. Because of the extensive production and use of DEHP, humans are exposed to this chemical daily. Diet is a significant exposure pathway and fatty food contain the highest level of phthalates. The impact on pregnancy following DEHP exposure and the associated interaction of high fat (HF) diet remains unknown. Here we report that exposure of pregnant mice to an environmentally relevant level of DEHP did not affect pregnancy. In contrast, mice fed a HF diet during gestation and exposed to the same level of DEHP display marked impairment in placental development, resulting in poor pregnancy outcomes. Our study further reveals that DEHP exposure combined with a HF diet interfere with the signaling pathway controlled by nuclear receptor PPARγ to adversely affect differentiation of trophoblast cells, leading to compromised vascularization and glucose transport in the placenta. Collectively, these findings demonstrate that maternal diet during pregnancy is a critical factor that determines whether exposure to an environmental toxicant results in impaired placental and fetal development, causing intrauterine growth restriction, fetal morbidity, and mortality.

  PublisherOA PDFDOI

• Msx Homeobox Genes Act Downstream of BMP2 to Regulate Endometrial Decidualization in Mice and in Humans

  Endocrinology · 2019-05-24 · 21 citations

  articleOpen access

  Endometrial stromal cells differentiate to form decidual cells in a process known as decidualization, which is critical for embryo implantation and successful establishment of pregnancy. We previously reported that bone morphogenetic protein 2 (BMP2) mediates uterine stromal cell differentiation in mice and in humans. To identify the downstream target(s) of BMP2 signaling during decidualization, we performed gene-expression profiling of mouse uterine stromal cells, treated or not treated with recombinant BMP2. Our studies revealed that expression of Msx2, a member of the mammalian Msx homeobox gene family, was markedly upregulated in response to exogenous BMP2. Interestingly, conditional ablation of Msx2 in the uterus failed to prevent a decidual phenotype, presumably because of functional compensation of Msx2 by Msx1, a closely related member of the Msx family. Indeed, in Msx2-null uteri, the level of Msx1 expression in the stromal cells was markedly elevated. When conditional, tissue-specific ablation of both Msx1 and Msx2 was accomplished in the mouse uterus, a dramatically impaired decidual response was observed. In the absence of both Msx1 and Msx2, uterine stromal cells were able to proliferate, but they failed to undergo terminal differentiation. In parallel experiments, addition of BMP2 to human endometrial stromal cell cultures led to a robust enhancement of MSX1 and MSX2 expression and stimulated the differentiation process. Attenuation of MSX1 and MSX2 expression by small interfering RNAs greatly reduced human stromal differentiation in vitro, indicating a conservation of their roles as key mediators of BMP2-induced decidualization in mice and women.

  PublisherOA PDFDOI

• Progesterone Signaling in the Endometrium

  Elsevier eBooks · 2018-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Genetic Mouse Models for Female Reproductive Toxicology Studies

  Elsevier eBooks · 2017-06-28 · 2 citations

  book-chapter1st authorCorresponding
  PublisherDOI

• Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

  PLoS ONE · 2016-10-24 · 82 citations

  articleOpen access

  Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

  PublisherOA PDFDOI

• Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice

  Endocrinology · 2016-03-29 · 90 citations

  articleOpen access

  Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.

  PublisherOA PDFDOI

• Rac1 Regulates Endometrial Secretory Function to Control Placental Development

  PLoS Genetics · 2015-08-25 · 31 citations

  articleOpen access1st author

  During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal-endothelial and stromal-trophoblast crosstalk critical for placenta development and establishment of pregnancy.

  PublisherOA PDFDOI

Frequent coauthors

• Indrani C. Bagchi

  University of Illinois Urbana-Champaign

  11 shared

• Milan K. Bagchi

  9 shared

• Paul S. Cooke

  University of Florida

  8 shared

• Jodi A. Flaws

  University of Illinois Urbana-Champaign

  8 shared

• Daniel R. Doerge

  6 shared

• Kellie A. Woodling

  6 shared

• Melissa A. Cimafranca

  United States Food and Drug Administration

  5 shared

• Quanxi Li

  Gansu Agricultural University

  5 shared