Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca fascicularis) following exposure to dioxin

Yumei Guo, Andrew G Hendrickx, James W. Overstreet, Jacquelyn Dieter, Dennis Stewart, Alice F Tarantal, Lisa Laughlin, Bill L. Lasley

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

This study examines the endocrine alterations associated with early fetal loss (EFL) induced by an environmental toxin, TCDD (2,3,7,8- tetrachlorodibenzo-p-dioxin), in the cynomolgus macaque, a well-documented reproductive/developmental model for humans. Females were administered single doses of 1, 2, and 4 μg/kg TCDD (n = 4 per dose group) on gestational day (GD) 12. Urinary estrogen metabolites (estrone conjugates) were monitored to establish the day of ovulation, and serum hormones (estradiol, progesterone, chorionic gonadotropin, relaxin) were measured to assess ovarian and placental endocrine status before and after treatment. EFL occurred between GDs 22 and 32 in 10 of the 12 animals treated with TCDD. The primary endocrine alterations associated with TCDD treatment were significant decreases in serum estradiol and bioactive chorionic gonadotropin concentrations (p < 0.02). Less pronounced decreases in serum progesterone (p = 0.10) and relaxin (p < 0.08) also followed TCDD treatment. In contrast, immunoreactive chorionic gonadotropin concentrations were not reduced by TCDD exposure at any level, indicating that TCDD targets specific components of the chorionic gonadotropin synthesis machinery within the trophoblast to alter the functional capacity of the hormone. These data demonstrate the value of endocrine biomarkers in identifying a toxic exposure to primate pregnancy many days before direct signs of reproductive toxicity were apparent. The increased EFL that occurred after exposure to TCDD might reflect a toxic response initially mediated via endocrine imbalance, leading to placental insufficiency, compromised embryonic circulation, and subsequent EFL.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalBiology of Reproduction
Volume60
Issue number3
StatePublished - 1999

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Fingerprint Dive into the research topics of 'Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca fascicularis) following exposure to dioxin'. Together they form a unique fingerprint.

  • Cite this

    Guo, Y., Hendrickx, A. G., Overstreet, J. W., Dieter, J., Stewart, D., Tarantal, A. F., Laughlin, L., & Lasley, B. L. (1999). Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca fascicularis) following exposure to dioxin. Biology of Reproduction, 60(3), 707-713.