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Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.

Publication ,  Journal Article
Burns, KA; Thomas, SY; Hamilton, KJ; Young, SL; Cook, DN; Korach, KS
Published in: Endocrinology
January 1, 2018

Endometriosis is a gynecological disease that negatively affects the health of 1 in 10 women. Although more information is known about late stage disease, the early initiation of endometriosis and lesion development is poorly understood. Herein, we use a uterine tissue transfer mouse model of endometriosis to examine early disease development and its dependence on estradiol (E2) and estrogen receptor (ER) α within 72 hours of disease initiation. Using wild-type and ERα knockout mice as hosts or donors, we find substantial infiltration of neutrophils and macrophages into the peritoneal cavity. Examining cell infiltration, lesion gene expression, and peritoneal fluid, we find that E2/ERα plays a minor role in early lesion development. Immune-mediated signaling predominates E2-mediated signaling, but 48 hours after the initiation of disease, a blunted interleukin (IL)-6-mediated response is found in developing lesions lacking ERα. Our data provide evidence that the early initiation of endometriosis is predominantly dependent on the immune system, whereas E2/ERα/IL-6-mediated cross-talk plays a partial role. These findings suggest there are two phases of endometriosis-an immune-dependent phase and a hormone-dependent phase, and that targeting the innate immune system could prevent lesion attachment in this susceptible population of women.

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Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

January 1, 2018

Volume

159

Issue

1

Start / End Page

103 / 118

Location

United States

Related Subject Headings

  • Signal Transduction
  • Random Allocation
  • Ovariectomy
  • Neutrophil Infiltration
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Macrophage Activation
  • Killer Cells, Natural
  • Interleukin-6
  • Immunity, Innate
 

Citation

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Burns, K. A., Thomas, S. Y., Hamilton, K. J., Young, S. L., Cook, D. N., & Korach, K. S. (2018). Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology, 159(1), 103–118. https://doi.org/10.1210/en.2017-00562
Burns, Katherine A., Seddon Y. Thomas, Katherine J. Hamilton, Steven L. Young, Donald N. Cook, and Kenneth S. Korach. “Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.Endocrinology 159, no. 1 (January 1, 2018): 103–18. https://doi.org/10.1210/en.2017-00562.
Burns KA, Thomas SY, Hamilton KJ, Young SL, Cook DN, Korach KS. Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology. 2018 Jan 1;159(1):103–18.
Burns, Katherine A., et al. “Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.Endocrinology, vol. 159, no. 1, Jan. 2018, pp. 103–18. Pubmed, doi:10.1210/en.2017-00562.
Burns KA, Thomas SY, Hamilton KJ, Young SL, Cook DN, Korach KS. Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology. 2018 Jan 1;159(1):103–118.
Journal cover image

Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

January 1, 2018

Volume

159

Issue

1

Start / End Page

103 / 118

Location

United States

Related Subject Headings

  • Signal Transduction
  • Random Allocation
  • Ovariectomy
  • Neutrophil Infiltration
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Macrophage Activation
  • Killer Cells, Natural
  • Interleukin-6
  • Immunity, Innate