About

Indrani C Bagchi is a professor in the Biomedical and Translational Sciences department at the Carle Illinois College of Medicine, University of Illinois Urbana-Champaign. She is involved in teaching courses such as Reproductive Physiology, Animal Sciences Seminar, and Structure and Function III. Her research focus includes biomedical and translational sciences, with recent news indicating her involvement in developing tools to track inflammation in human tissue in collaboration with the Chan Zuckerberg Biohub Chicago Investigators. She contributes to the college's mission of reengineering medicine through her academic and research activities, supporting innovation and translational research in health sciences.

Research topics

• Biology
• Endocrinology
• Genetics
• Physiology
• Chemistry
• Cell biology
• Cancer research
• Medicine
• Bioinformatics
• Internal medicine
• Andrology
• Immunology

Selected publications

• Deciphering the maternal uterine signals that shape placenta development

  Reproduction · 2026-05-01

  article

  In brief: Proper placental development depends not only on fetal trophoblast signaling but also on critical maternal uterine signals. This review highlights how decidual factors and maternal-fetal crosstalk regulate trophoblast invasion and placentation. Abstract: In humans and rodents, proper formation of a hemochorial placenta is essential for a successful pregnancy, as the placenta serves as the maternal-fetal interface that facilitates the exchange of nutrients, gases, and waste between the mother and the developing fetus. The fetal compartment of the placenta is formed by extraembryonic trophoblast cells that proliferate and differentiate into distinct lineages that play specialized roles during placental development. Trophoblast lineage development and function are highly dependent upon embryonic paracrine signaling and timely activation of transcription factors within the trophoblasts. However, recent studies have increasingly emphasized the critical role of maternal factors in regulating trophoblast differentiation and placental development. Notably, conditional knockout mouse models have demonstrated the essential contribution of maternal decidual expression of specific molecular signals in orchestrating these processes. In this review, we summarize the role of maternal uterine signals in shaping placental development. We examine the role of decidua-derived secreted factors in directing trophoblast lineage specification and promoting appropriate levels of trophoblast invasion. Additionally, we explore the crosstalk between maternal- and fetal-derived signals that collectively regulate the extent and timing of trophoblast invasion into the uterine tissue. The interplay between maternal immune cells and trophoblasts is also discussed, with a focus on mechanisms that not only support immune tolerance to the semi-allogeneic placenta but also mediate trophoblast invasion and vascular remodeling. Finally, we consider the clinical implications of maternal influences on placentation, including the emerging potential of decidual extracellular vesicles as non-invasive biomarkers for pregnancy health and placental dysfunction.

  PublisherDOI

• Human Decidual RUNX1 Promotes Angiogenesis and Trophoblast Differentiation by Regulating Extracellular Vesicle Signaling

  Endocrinology · 2025-08-29 · 1 citations

  articleOpen access

  During early pregnancy, human endometrial stromal cells differentiate into secretory decidual cells via a process regulated by ovarian steroid hormones. Decidual cells play a crucial role by secreting various factors that support essential events in forming a functional placenta, including uterine angiogenesis and the differentiation and development of trophoblasts. We previously reported that the conditional ablation of the transcription factor runt-related transcription factor 1 (RUNX1) in the mouse uterus leads to subfertility due to insufficient maternal angiogenesis and impaired trophoblast differentiation. In this study, we examined the role of RUNX1 in facilitating communication mechanisms among human decidual cells and other cell types present in the pregnant uterus. We demonstrate that RUNX1 regulates the conserved hypoxia-inducible factor 2 α-RAB27B pathway in primary human endometrial stromal cells (HESCs) during decidualization, which promotes the secretion of extracellular vesicles (EVs) by these cells. Consequently, the depletion of RUNX1 in HESC led to reduced EV secretion. Mass spectrometry identified several cargo proteins in decidual EVs, including angiopoietin-related protein 2 (ANGPTL2) and IGF2, which could regulate angiogenesis or trophoblast differentiation. We found that RUNX1 directly regulates their expression, resulting in partial changes to these cargoes when it is absent. We observed that delivering EVs lacking ANGPTL2 or IGF2 to human endothelial cells significantly decreased the formation of vascular networks compared to introducing control EVs carrying these factors. Furthermore, adding IGF2-depleted EVs to human trophoblast cells inhibited their differentiation into the extravillous trophoblast lineage. These findings collectively highlight the crucial role of decidual RUNX1 in promoting essential cell-cell interactions for angiogenesis and trophoblast differentiation during placenta formation.

  PublisherOA PDFDOI

• Phthalates Impair Estrogenic Regulation of HIF2α and Extracellular Vesicle Secretion by Human Endometrial Stromal Cells

  Endocrinology · 2025-04-22 · 3 citations

  articleOpen access

  High levels of exposure to di(2-ethylhexyl) phthalate (DEHP), a known endocrine disruptor, have been linked to adverse pregnancy outcomes, yet the mechanisms by which it impacts human uterine functions remain unclear. Here we report that exposure of differentiating primary human endometrial stromal cells (HESCs) to an environmentally relevant concentration of DEHP or its primary metabolite, mono(2-ethylhexyl) phthalate, markedly reduces the expression of the estrogen-regulated transcription factor hypoxia-inducible factor 2-α (HIF2α). We also noticed a simultaneous decrease in RAB27B expression, which is crucial for the trafficking and secretion of extracellular vesicles (EVs). EVs enhance communication among various cell types within the pregnant uterus, thereby ensuring reproductive success. We found that estrogen receptor α (ERα) could no longer bind to the HIF2α regulatory region following phthalate treatment, and epigenetic analysis suggested that this may be due to hypermethylation of nearby CpG islands. Further investigation revealed a potential interaction between ERα and the transcription factor specificity protein 1 (Sp1) within the HIF2α regulatory region, which is affected by the inhibition of Sp1 binding to the phthalate-induced hypermethylated DNA. Additionally, our results suggest that the abnormal DNA methylation is likely due to increased expression of the DNA methyltransferase 1 (DNMT1) gene in response to phthalate exposure. Overall, this study provides valuable mechanistic insights into how phthalate-induced differential DNA methylation disrupts estrogenic regulation of the HIF2α gene and, consequently, EV secretion during HESC differentiation. This knowledge is essential for understanding how phthalates may lead to adverse reproductive outcomes by disrupting hormonal regulation of cell-to-cell communication in the uterus.

  PublisherOA PDFDOI

• 2323P The role of non-OS endpoints in addressing unmet need associated with the SoC in locally advanced rectal cancer

  Annals of Oncology · 2025-09-01

  articleSenior author
  PublisherDOI

• Exposure to phthalates enhances estrogen and beta-catenin signaling pathways, leading to endometrial hyperplasia in mice

  Toxicological Sciences · 2025-05-05 · 4 citations

  articleOpen accessSenior author

  Phthalates, synthetic chemicals widely utilized as plasticizers and stabilizers in various consumer products, present a significant concern due to their persistent presence in daily human life. Although past research predominantly focused on individual phthalates, real-life human exposure typically encompasses complex mixtures of these compounds. The cumulative effects of prolonged exposure to phthalate mixtures on uterine health remain poorly understood. To address this knowledge gap, we conducted studies utilizing adult female mice exposed chronically to a mixture of phthalates for 12 mo through ad libitum chow consumption. Our studies revealed that continuous exposure to this phthalate mixture led to uterine hyperplasia with a significant increase in gland-to-stroma ratio. Endometrial hyperplasia is commonly caused by heightened estrogenic action and inflammatory response in the uterus, leading to increased proliferation of endometrial epithelial cells. Indeed, we observed a marked upregulation of several known estrogen-regulated genes, proinflammatory chemokines, elevated homing of macrophages, and increased KI67 staining in the endometrial epithelial cells upon phthalate exposure. Several signaling pathways, including the MAPK/ERK and Wnt/β-Catenin pathways, promote cell proliferation, leading to the hyperproliferative state of the endometrial cells. Our studies revealed no alteration of the MAPK/ERK pathway but a marked enhancement of the Wnt/β-Catenin signaling pathway in phthalate-exposed uteri. Collectively, this study underscores the significance of understanding the exposure to environmental factors in the pathogenesis of endometrial disorders.

  PublisherOA PDFDOI

• Human Decidual RUNX1 Promotes Angiogenesis and Trophoblast Differentiation by Regulating Extracellular Vesicle Signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-14 · 1 citations

  preprintOpen access

  During early pregnancy, human endometrial stromal cells differentiate into secretory decidual cells via a process regulated by ovarian steroid hormones. Decidual cells play a crucial role by secreting various factors that support essential events in forming a functional placenta, including uterine angiogenesis and the differentiation and development of trophoblasts. We previously reported that the conditional ablation of the transcription factor RUNX1 in the mouse uterus leads to subfertility due to insufficient maternal angiogenesis and impaired trophoblast differentiation. In this study, we examined the role of RUNX1 in facilitating communication mechanisms among human decidual cells and other cell types present in the pregnant uterus. We demonstrated that RUNX1 regulates the conserved HIF2α-RAB27B pathway in primary human endometrial stromal cells (HESC) during decidualization, which promotes the secretion of extracellular vesicles (EVs) by these cells. Consequently, the depletion of RUNX1 in HESC led to reduced EV secretion. Mass spectrometry identified several cargo proteins in decidual EVs, including ANGPTL2 and IGF2, which could regulate angiogenesis or trophoblast differentiation. We found that RUNX1 directly regulates their expression, resulting in partial changes to these cargoes when it is absent. We observed that delivering EVs lacking ANGPTL2 or IGF2 to human endothelial cells significantly decreased the formation of vascular networks compared to introducing control EVs carrying these factors. Furthermore, adding IGF2-depleted EVs to human trophoblast cells inhibited their differentiation into the extravillous trophoblast lineage. These findings collectively highlight the crucial role of decidual RUNX1 in promoting essential cell-cell interactions for angiogenesis and trophoblast differentiation during placenta formation.

  PublisherOA PDFDOI

• Impact of paraben on uterine collagen: An integrated and targeted Correlative approach using second harmonic generation microscopy, nanoindentation, and atomic force microscopy

  Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · 2025-02-01 · 1 citations

  articleOpen access

  This study investigates the structural and mechanical changes in uterine collagen following exposure to propylparaben (PP) using a combined methodology of Second Harmonic Generation (SHG) microscopy, Nanoindentation (NI), and Atomic Force Microscopy (AFM). SHG analysis identified significant disorganization in collagen fibril orientation in the circumferential layer and heterogeneous distribution of regions with elevated forward to backward ratios (F/B) across all uterine layers due to PP exposure. High F/B can indicate multiple potential fibril-level changes like thickened fibrils, higher crosslinking, fibril disorganization - changes not fully decipherable by SHG alone. Recognizing this limitation, the study employs NI and AFM to provide complementary mechanical and nanoscale insights. NI revealed increased indentation modulus in the exposed uteri, suggesting increased stiffness. Co-registration of the indentation response with SHG parameters uncovered that elevated F/B regions show enhanced mechanical stiffness, suggesting a fibrotic transformation following chronic PP exposure. AFM was specifically performed on regions identified by SHG as having low or high F/B, providing the necessary nanoscale resolution to elucidate the structural changes in fibrils that are likely responsible for the observed alterations. AFM confirmed the presence of disordered and entangled collagen fibrils in the circumferential layer in all regions and an increase in fibril diameter in the high F/B regions in the PP-exposed uteri. Together, these findings demonstrate significant alterations in collagen architecture due to PP exposure, revealing disruptions at both the fiber and fibril levels and highlighting the potential for broader applications of the multi-scale, multi-modal approach in collagenous tissue studies. • Paraben disrupts collagen structure in the uterus circumferential layer (SHG, AFM). • Paraben elevates the forward/backward signal intensity ratio (F/B) in uterus (SHG). • High F/B regions are heterogeneous in all layers in paraben exposed uteri (SHG). • Higher indentation modulus in high F/B regions, suggesting fibrosis (indentation). • Thicker and disorganized fibrils in high F/B regions, also indicating fibrosis (AFM).

  PublisherDOI

• Uterus: Growth Factors and Cytokines

  Elsevier eBooks · 2024-07-07

  book-chapterSenior author
  PublisherDOI

• Phthalates Impair Estrogenic Regulation of HIF2α and Extracellular Vesicle Secretion by Human Endometrial Stromal Cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-17

  preprintOpen accessCorresponding

  Abstract Di(2-ethylhexyl) phthalate (DEHP), a known endocrine-disrupting chemical, is a plasticizer found in many common consumer products. High levels of DEHP exposure have been linked to adverse pregnancy outcomes, yet little is known about how it affects human uterine functions. We previously reported that the estrogen-regulated transcription factor hypoxia-inducible factor 2 alpha (HIF2α) promotes the expression of Rab27b, which controls the trafficking and secretion of extracellular vesicles (EVs). EVs facilitate communication between multiple cell types within the pregnant uterus, ensuring reproductive success. In this study, we report that exposure of differentiating primary human endometrial stromal cells (HESC) to an environmentally relevant concentration (1 μg/mL) of DEHP or its primary metabolite mono(2-ethylhexyl) phthalate (MEHP) markedly reduces the expression of HIF2α . We also observed a concomitant decrease in RAB27B expression, reducing EV secretion from HESC. Interestingly, we found that DEHP or MEHP exposure disrupts estrogenic regulation of the HIF2α/Rab27b signaling pathway. Estrogen receptor alpha (ERα) could no longer bind to the HIF2α regulatory region following phthalate treatment, and epigenetic analysis suggested that this may be due to hypermethylation of nearby CpG islands. Further investigation revealed a potential interaction between ERα and the transcription factor Sp1 within the HIF2α regulatory region, which is affected by the inhibition of Sp1 binding to the phthalate-induced hypermethylated DNA. Additionally, our results suggest that the abnormal DNA methylation is likely due to increased expression of the DNA methyltransferase 1 ( DNMT1 ) gene in response to phthalate exposure. Overall, this study provides valuable mechanistic insights into how phthalate-induced differential DNA methylation disrupts estrogenic regulation of the HIF2α gene and, consequently, EV secretion during HESC differentiation. This knowledge is crucial for our understanding of how phthalates may cause adverse reproductive outcomes by disrupting the hormonal regulation of cell-to-cell communication within the pregnant uterus.

  PublisherOA PDFDOI

• Interleukin-1β induces and accelerates human endometrial stromal cell senescence and impairs decidualization via the c-Jun N-terminal kinase pathway

  Cell Death Discovery · 2024-06-15 · 30 citations

  articleOpen access

  As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that "inflammaging" contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.

  PublisherOA PDFDOI

Recent grants

• Role of Hypoxia in Regulating Stromal-Epithelial Communication during Pregnancy

  NIH · $1.6M · 2018–2024

• NIH Grant U54HD029990

  NIH · $55.5M · 2017

• NIH Grant R01HD034527

  NIH · $1.3M · 2004

• NIH Grant U01HD034760

  NIH · $824k · 2001

• Gender and sex differences in phthalate-induced toxicity in the reproductive system

  NIH · $2.2M · 2020–2025

Frequent coauthors

• Milan K. Bagchi

  179 shared

• Quanxi Li

  Gansu Agricultural University

  47 shared

• Athilakshmi Kannan

  42 shared

• Francesco J. DeMayo

  National Institute of Environmental Health Sciences

  36 shared

• Mary J. Laws

  University of Illinois Urbana-Champaign

  35 shared

• Robert N. Taylor

  Jacobs (United States)

  31 shared

• John P. Lydon

  Baylor College of Medicine

  31 shared

• Li-Ji Zhu

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  15 shared