Placental apoptosis in normal pregnancy & IUGR

1. Placental apoptosis in normal pregnancy & IUGR
Aboubakr Elnashar, Eman Elnashar , Ahmed Sherief
Benha University, Egypt

2. History
• Apoptosis was first described in 1972 by
Kerr et al .
• It was not widely accepted until recently.
• Since 1980, molecular biological
techniques have led to rapid advances in
knowledge of this process.
ABOUBAKR ELNASHAR

3. Definition
• Apoptosis derives from the Greek description of
the ( dropping off ) or
( falling away ) of petals from flowers or leaves
from trees.
• It is a programmed cell death.
• It is an active cell death.
• It plays a role opposite to mitosis.
ABOUBAKR ELNASHAR

4. Necrosis Apoptosis
Define Accidental cell death,
cauesd by factors
external to the cell
Active cell death
dependent on
internal machinery
cell
Stimuli Hypoxia, toxins Physiological or
pathological
Histology Cellular swelling
Coagulation necrosis
Disruption of
organelles
Single cells
Chromatin
condensation
Apoptotic bodies
DNA break
down
Random,diffuse ATP
depletion
Membrane. Injury
Free radical damage
Internucleosomal
Gene activation
Endonuclease
Tissue
reaction
inflammation No inflammation
Phagocytosis of
apoptotic bodies
ABOUBAKR ELNASHAR

5. Biochemical events
The hallmark is rapid nuclear DNA cleavage
• DNA cleavage into 200-300 kilobase filaments
• Double stranded cleavage of the
internucleosomal DNA
Candidate enzymes : DNAse I & DNAse II
Genetic regulation
Genes implicated : C-myc , P53 , B C 1-2
ABOUBAKR ELNASHAR

6. Detection
Morphological changes is the most reliable evidence of apoptosis
I. Light microscopy
II. Electron microscopy : The surest
III. End labeling of cleaved DNA :1. TUNEL
2. ISEL
IV. Electrophoresis : 1. DNA agarose gel
2. Pulse-field gel
V. Flow cytometry
ABOUBAKR ELNASHAR

7. Physiological examples :
1. During embryogenesis ( implantation,
organogenesis, involution of M &Wducts, generation of
lumina within a viscera e.g heart.
2. Deletion of self reactive colones during development
of the immune system.
3. Normal cell turnover in g.I.t epi. S.N tubules & L.N
4. Hormone dependent involution ( endometrial cell
during menstrual cycle, ovarian follicular atresia in
menopause, lactating breast after weaning
ABOUBAKR ELNASHAR

8. Pathological examples
1. All forms of neoplastic growths, both during growth & regression
2. In tissues exposed to low doses of toxic stimuli
( hyperthermia, radiation, cytotoxic drugs,hypoxia )
3.T-cell mediated apoptotic cell death( transplant rejection,
graft-versus-host dis., viral dis.; hepatitis& HIV )
4. Regression of tissue hyperplasia once the stimulus is removed
5. Atrophy of parenchymal organs after duct
obstruction(kidney, pancreas, parotid )ABOUBAKR ELNASHAR

9. Placental apoptosis
•Recently, in 1996, placental apoptosis has been reported
•Apoptosis was identified in all cell types of the placenta.
More than 50% was identified in the trophoblast
particularly the syncytotrophoblast.
•In 1997, Smith et al reported that placental apoptosis
increases significantly as pregnancy progresses,
suggesting that its important role in the physiologic &
pathologic mechanisms of the placenta
•Research is still in an early stage, but interest is rapidly growingABOUBAKR ELNASHAR

10. To investigate the possible role for
apoptosis in thepathophysilogic
mechanisms of intrauterinegrowth
restriction
ABOUBAKR ELNASHAR

11. Placental samples were obtained from
30 normal uncomplicated third trimester pregnancies&
20 third trimester pregnancies complicated by IUGR.
Exclusion criteria : prolonged ROM or IU infection
• Light microscopy :
•TUNEL staining( Terminal deoxytransferase deoxy Uridine triphosphate Nick End
Labelling )
•Electron microscopy : 5 cases
ABOUBAKR ELNASHAR

12. Normal
(n=30)
IUGR
(n=20)
Sig
Age (Y) 29(25-31) 3(026-33) NS
G.age (W) 39 (38-41) 38(35-39) S
Parity 1(0-2) 1(0-2) NS
B.weight (Kg) 3.5(3.3-3.9) 2.3(1.9-2.6) S
Mode of delivery
. Normal
. Instrumental
. C.S
16
3
11
5
1
14
S
Patients characteristics
ABOUBAKR ELNASHAR

13. Normal
(n=30)
IUGR
(n=20)
Median Range Median Range
Sig
L.microscopy 0.15 0.9-0.21 0.25 0.16-0.31 S
TUNEL 0.29 0.19-0.43 0.48 0.29-0.59 S
Incidence of placental apoptosis of both
groups ( % )
ABOUBAKR ELNASHAR

14. • Whether increased placental apoptosis in IUGR is the
cause or the result ?
• Further research is required to identify the extrinsic
proteins involved in control of placental apoptosis
. Insulin like growth factor-I
. Platelet-derived growth factor
. Endothelial growth factor
• Identification of the pathogenesis of IUGR could provide
the basis for therapeutic interventions.
ABOUBAKR ELNASHAR