scholarly journals n-Butyl Benzyl Phthalate Exposure Promotes Lesion Survival in a Murine Endometriosis Model

2021 ◽  
Vol 18 (7) ◽  
pp. 3640
Author(s):  
Pooja Sharma ◽  
Jo-Yu Lynn Lee ◽  
Eing-Mei Tsai ◽  
Yu Chang ◽  
Jau-Ling Suen
Keyword(s):  
Chronic Exposure ◽  
Low Dose ◽  
Estrogenic Activity ◽  
Estrus Cycle ◽  
Endometriotic Lesion ◽  
Multiparametric Flow Cytometry ◽  
Butyl Benzyl Phthalate ◽  
Environmental Endocrine Disruptors ◽  
Lesion Growth ◽  
Gynecological Disease

Endometriosis is an inflammatory and estrogen-dependent gynecological disease associated with exposure to environmental endocrine disruptors. n-Butyl benzyl phthalate (BBP), a ubiquitous plasticizer, has weak estrogenic activity, and exposure to BBP is associated with endometriosis. We aimed to elucidate the immunomodulatory effect of BBP on endometriosis development. We previously established a surgery-induced endometriosis-like murine model. In the present study, we exposed those mice to BBP 10 days prior to surgery and 4 weeks after surgery at physiologically relevant doses to mimic human exposure. Chronic exposure to BBP did not promote the growth of endometriotic lesions; however, the lesion survival rate in BBP-treated mice did increase significantly compared with control mice. Multiparametric flow cytometry showed that BBP exposure did not affect the homeostasis of infiltrated immune subsets in lesions but did enhance CD44 (adhesion marker) expression on plasmacytoid dendritic cells (pDCs). Blocking CD44 interactions locally inhibited endometriotic lesion growth. Immunofluorescence results further confirmed that CD44 blocking inhibited pDC infiltration and reduced the frequency of CD44+ pDCs in endometriotic tissues. BBP also disrupted the estrus cycle in these mice. This study suggests that chronic exposure to low-dose BBP may promote survival of endometriotic tissue through CD44-expressing pDCs.

19. Anti-Angiogenic Therapy for Endometriosis

2018 ◽  
Author(s):  
Privia Randhawa
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Blood Supply ◽  
Uterine Cavity ◽  
Growth And Survival ◽  
Angiogenic Therapy ◽  
Lesion Growth ◽  
Gynecological Disease ◽  
Stromal Cell Derived Factor ◽  
Survival Studies

Endometriosis is a gynecological disease affecting 10 to 15% women. The disease is characterized by the growth of endometrium (lining of the uterus) outside of the uterine cavity. Women affected by this condition can experience symptoms that include pelvic pain, irregular bleeding, and infertility. One of the key requirements for endometriotic lesions to survive is to develop a blood supply to support their growth. Our laboratory is investigating mechanisms of how endometriotic lesions establish their blood supply and how neo-angiogenesis is regulated by endothelial and hematopoietic progenitor cells. Results from our laboratory showed that stromal cell derived factor-1 plays an important role in the recruitment of endothelial progenitor cells. Blocking of SDF-1 in a mouse model of endometriosis resulted in reduced lesion growth and survival. Studies are in progress to evaluate safety and efficacy of anti-angiogenic peptide, ABT-898, in an immunodeficient mouse model of endometriosis. 

scholarly journals A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sophia Murat El Houdigui ◽  
Christelle Adam-Guillermin ◽  
Giovanna Loro ◽  
Caroline Arcanjo ◽  
Sandrine Frelon ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Nuclear Power ◽  
Muscle Development ◽  
Low Dose ◽  
Neuromuscular Junctions ◽  
Biological Effects ◽  
Cardiac Activity ◽  
Developmental Defects ◽  
Dose Rates ◽  
Larval Behaviour

AbstractContamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.

A prominent environmental endocrine disruptor, 4-nonylphenol, promotes endometriosis development via plasmacytoid dendritic cells

2020 ◽  
Vol 26 (8) ◽  
pp. 601-614
Author(s):  
Pooja Sharma ◽  
Hsin-Han Tseng ◽  
Jo-Yu Lynn Lee ◽  
Eing-Mei Tsai ◽  
Jau-Ling Suen
Keyword(s):  
Dendritic Cells ◽  
Endocrine Disruptor ◽  
Apoptotic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Local Treatment ◽  
Dependent Manner ◽  
Endometriotic Lesion ◽  
Lesion Development ◽  
Lesion Growth

Abstract Endometriosis is an estrogen-dependent chronic inflammatory disease and is associated etiologically with environmental endocrine disruptor (EED) exposure. 4-nonylphenol (NP), a widely found EED, has weak estrogenic activity and modulates plasmacytoid dendritic cell (pDC) function in vitro and in vivo. We aimed to elucidate the immunomodulatory effect of NP on the development of endometriosis, particularly focusing on pDCs. This study established a surgically induced endometriosis murine model (C57BL/6) under conditions of NP treatment that are relevant to the level and route of human exposure. Multi-parametric flow cytometry was used for analysis of infiltrated immune cell subsets in lesions. The results showed that NP exposure significantly promoted endometriotic lesion growth, survival and angiogenesis development of lesions as well as pDC accumulation in the lesions in mice. Adoptive transfer of NP-conditioned pDCs into mice significantly enhanced lesion development and local pDC infiltration, whereas NP-conditioned conventional dendritic cells did not affect lesion growth. In vitro functional analysis showed that NP-conditioned pDCs in lesions expressed high levels of CD36, a scavenger receptor and NP-conditioned splenic pDCs secreted an enhanced level of IL-10 in response to apoptotic cell recognition in a CD36-dependent manner. Furthermore, we observed that local treatment with blocking antibodies against IL-10 and CD36 on the day of surgery significantly inhibited lesion development. NP exposure also altered the estrous cycle in mice. The results suggest that chronic and low-dose exposure to NP enhances endometriotic lesion growth by altering pDC homeostasis and function. This study has important implications for understanding the environment-innate immunity interaction in human endometriosis.

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