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Histology of Postnatal

Development of the Rat.

Part I

Catherine Picut, VMD, JD, DACVP, DABT

catherine.picut@crl.com

IATP-ESTP 20Sept2016

Outline of Presentation

• Microscopic Development of Selected Tissues

- Brain, Testis, Ovary, Lung, Thyroid

- Point out: critical time points, diagnostic

pitfalls, & biologically interesting features

Post-natal developmental stages

Stage Rat Human

Neonatal 0 - 7 d 0 – 28 days

Infantile 8 – 20 d 1 – 23 months

Juvenile 21 – 32 d 2 – 12 years

Peripubertal 33 – 55 d 13 – 16 years

Brain

Changes in composition of brain

•

Cortical neurons

0 7 14 21 … 37

Cerebellar &

Hippocampal

& Olfactory

Bulb neurons

Postnatal days in rat

Number

Human brain at birth

PND 1 Brain 1.25x

PND 21 cerebellum

Secondary Germinal Matrix

Purkinje

Granular Cell

Primary Germinal Matrix

4th Ventricle

Pia

Development of the Layers of the Cerebellum

PND 1 Cerebellum

PND 7 cerebellum 40x

PND 14 cerebelllum

PND 21 cerebellum

PND 1 Cortex: motor

PND 7: Cortex: motor

PND 6 Brain: motor Caspase-3 40x

PND 7 Deep Cerebellar Nucleus

PND 21 cortex (motor) 20x

Choroid Plexus PND 1 (vacuolated)

Brain – summarized points

• Neurons are developed by time of birth

• Postnatal development of neurons limited to:

– Cerebellum (granular cell layer)

– Olfactory Bulbs

– Hippocampus

• Apoptosis of cortical neurons is normal from PND

1 – PND 14 (Peak around PND 7)

• Vacuolation of choroid plexus is normal from birth

to about PND 14.

TESTES

180 46

Postnatal day

Spermatogonia

Sertoli cells

BTB

First Wave of Spermatogenesis

Uniform Tubules / No Staging

Unique Cell Types

Unique Cell Distribution

Testis PND 3 (Neonatal) 40x

PND 9 (Early Infantile)

Testis PND 15 (Late Infantile) 57x

PND 18 Testis PAS stain 60x

L

PND 27 (Juvenile): Normal apoptosis

PND 28 Testis/Epididymis; Exfoliation

Summary about Testis

Apoptosis is normal in

– late infantile period (PND 15-18)

– juvenile period (PND 27)

– Don’t confuse early spermatocytes with necrosis

Critical Window (PND 5 – 15)

-- significant, uniform, susceptible cell populations.

Unique cell distributions (PND 0 - PND 30)

OVARY

Ovary. PND 13: “Atypical” follicles

are normal

Ovary PND 27 Atresia

PND 35 Ovary

Picut C A et al. Toxicol Pathol 2013;42:403-413

PND 20 PND 25

PND 29 PND 32

PND32

RAT: VAGINA

Summary about Ovary

– Atypical follicles in young animal are normal (PND 10-

16).

– Apoptosis/atresia is normal in late juvenile period (PND

26-28)

– Corpora lutea >PND35

– The vagina will “mature” prior than the ovary.

Thyroid Gland

Thyroid Gland

• Thyroid gland is histologically mature by PND 7

• Thyroid Gland in rat at birth is equivalent to a

human at 5 months of pregnancy.

• Most dramatic changes occur GD 20 – PND 5

GD 20 PND 3 PND 10-30

Thyroid Gland PND 15

male

female

Epithelial cell height

Thyroid Gland PND 42 Male

Lung

Development of Lung in Rat

http://www.ana.unibe.ch/users/schittny/public_html/Reprints/Schittny2008Fishman.pdf

saccular

Alveolar “Double

capillary” “Single

capillary” due

to merging of

capillaries

Lung PND1 Saccular Stage

Lung PND 14 Bulk Alveolarization

Lung PND 15 “bulk alveolarization”

PND 21 (mature septae)

Issues/Concern about Lung

• Immature lung could be confused with interstitial

pneumonia or atelectasis. Elastin stains may

help identify immaturity.

• Hyperoxia can cause “delayed maturation” of

lung (animal model for premature births).

• Steroids/retinoids can cause “precocious”

maturation of lung – interstitium thins but doesn’t

septate properly

End of Part I