PMID- 10026120
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20190513
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 60
IP  - 3
DP  - 1999 Mar
TI  - Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca 
      fascicularis) following exposure to dioxin.
PG  - 707-13
AB  - 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 microgram/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.
FAU - Guo, Y
AU  - Guo Y
AD  - California Regional Primate Research Center, University of California at Davis, 
      Davis, California 95616-8542, USA.
FAU - Hendrickx, A G
AU  - Hendrickx AG
FAU - Overstreet, J W
AU  - Overstreet JW
FAU - Dieter, J
AU  - Dieter J
FAU - Stewart, D
AU  - Stewart D
FAU - Tarantal, A F
AU  - Tarantal AF
FAU - Laughlin, L
AU  - Laughlin L
FAU - Lasley, B L
AU  - Lasley BL
LA  - eng
GR  - ES04699/ES/NIEHS NIH HHS/United States
GR  - ES06198/ES/NIEHS NIH HHS/United States
GR  - RR00169/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Biomarkers)
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 9002-69-1 (Relaxin)
SB  - IM
MH  - Abortion, Spontaneous/chemically induced
MH  - Animals
MH  - Biomarkers/*analysis
MH  - Chorionic Gonadotropin/blood
MH  - Environmental Pollutants/*toxicity
MH  - Estradiol/blood
MH  - Female
MH  - Fetal Death/chemically induced/*diagnosis
MH  - Macaca fascicularis
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Pregnancy Outcome
MH  - Progesterone/blood
MH  - Relaxin/blood
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1095/biolreprod60.3.707 [doi]
PST - ppublish
SO  - Biol Reprod. 1999 Mar;60(3):707-13. doi: 10.1095/biolreprod60.3.707.