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Disruption of Brain Development and Reproductive Behavior of Birds DM Fry, JR Millam, AL Erichsen, MA Viant, AE Quaglino, CB Craig-Veit, and LA Preston. Dept of Animal/Avian Sci. University of Calif. Davis
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Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

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Page 1: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Disruption of Brain Development and Reproductive Behavior of Birds

DM Fry, JR Millam, AL Erichsen, MA Viant, AE Quaglino, CB Craig-Veit, and LA Preston.

Dept of Animal/Avian Sci.University of Calif. Davis

Page 2: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Extrapolation of xenobiotic exposure to the “real world”

• Methoxychlor, dicofol, and alkylphenols in agriculture in Yolo Co.

• Application rates and acreages available.

• Sensitivity of local species unknown

Page 3: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Current research on songbirds

• Altricial chicks require extended parental care

• Complex, but well understood brain neuroanatomy and physiology

• Song system is estrogen sensitive

• Brain is dimorphic Zebra Finches

Page 4: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Hormonal Influence in Brain Differentiation

• Testosterone produced by neo-natal male gonads • Uptake and aromatization by specific areas of

brain• Estrogen modulates differentiation of male

specific nuclei. Mechanism uncertain, BDNF clearly involved, apoptosis?

Page 5: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Dosing and testing protocol

• Oral gavage• 5-11 days post hatch• 1µl / g body wt. / day in

canola oil• parental care of chicks for

30-40 days• mixed sex juvenile cages

• Behavioral testing at 120+ days

• Behavior assessed with stimulus males and females on alternate days

• Testosterone implants to force/enable altered behavior

• Histology of brain, gonad

Page 6: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Effective doses given to finches(µg /g/body wt. /day)

• Estradiol benzoate: 2.7

• Methoxychlor: 35

• Octylphenol: 21

• Dicofol: 37

Page 7: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Extrapolated dose to nestling songbirds

• Body wt. During sensitive period: 3-10g• Food consumption: 1-8 g insects / day

• Dicofol @ 189 ppm, Exposure dose is 189-1512µg/day

• Octylphenolpolyehoxylate @ 22ppm: Exposure dose is 22-176µg/day

Page 8: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

"Broodiness" of Male Zebra Finches

0102030405060708090

100

Canola

Oil

10mM EB

100m

M EB10

00mM EB

100m

M OP

1000

mM OP

100m

M MXC

1000

mM MXC

100m

M D

% m

ales

nes

t per

chin

g

% males nest perching before TP

% males nest perching after TP

only 1 data point

Page 9: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Summary of Effects on Males

• Estradiol and Xenoestrogens active orally• Microgram per day doses cause changes in male

default behavior patterns:• Latency for courtship song• Reduced copulation • “Broodiness” • Responses in both Zebra Finches and Japanese Quail

Page 10: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Differentiation of brain and behavior in birds:

Female Zebra Finch

• Song System:• Passerine birds only• Species specific patterns in

dimorphism• Estrogen sensitive during

post-natal development

Page 11: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Zebra Finch “Song Circuitry”

• Learning and memory pathways in blue

• Motor pathway in red• Males sing, females do

not

David Clayton, Univ Illinois

Page 12: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Threshold for enablingThreshold for enablingsong is about 125µmsong is about 125µm33

Page 13: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive
Page 14: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Vocalizations of captive Zebra finches

• Male Zebra Finch

• Distance Calls

• Chatter (“tet” call)

• Courtship song

Page 15: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Vocalizations of female zebra finches

• Normal Females• “tet” call

• distance call

• “Male type” songs by sensitive exposed females

Page 16: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Female Finches Singing Courtship Song

0

2

4

6

8

10

12

Cano

la Oil

10mM EB

100m

M EB

1000

mM EB

100m

M OP

1000

mM OP

100m

M MXC

1000

mM MXC

100m

M D

# fe

ma

le f

inch

es

# Females singing

# Females tested to date

Page 17: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Estrogen and xenoestrogen induced changes in female finches

• Sexually dimorphic brain nuclei induced (retained? / enhanced?)

• Singing enabled in exposed females

• Aggressive behavior in many females

• Significant phenotypic variability by family

Page 18: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Reproductive Performance Tests

• Neonatal Dosing of zebra Finches, days 5-11– Estradiol benzoate 27µg/gBW/day– Octylphenol 21µ g/gBW/day

• Group caging: 6 pair per cage• Dosed males and females together• Dosed birds with control mates• Reproductive activity from Day 140

Page 19: Disruption of Brain Development and Reproductive Behavior of Birdse.hormone.tulane.edu/PDFs/proceedings-1999/Fry.pdf · 2003-05-09 · Disruption of Brain Development and Reproductive

Reproductive Activity:

• Estradiol females lay eggs, clutch size similar• No eggs hatch from treated group

– dosed males and females together– eggshell thinning in most females

• Mixed pair trials in progress:– some fertility and hatching success.