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Dept. of Nutritional Medicine, IRSHA & Dept. of Ob&Gy, Bharati Hospital, Bharati Vidyapeeth Deemed
OriginDevelopment Origin of Health & Diseases Hypothesis
FetusMother Adulthood
(Fall, 2013)
Pregnancy
Disorders
Altered Materna
l Nutritio
n
Placental Malfunctio
ning
Adverse Fetal
Programming
High Risk of NCDs
PREECLAMPSIA (PE)
Characteristics:
Hypertension: Systolic BP≥140 and Diastolic BP≥90
Proteinuria: >1+ or 300mg after 20 weeks of gestation
Prevalence:
Worldwide 2% to 8% of all pregnancies, majorly developing countries (Jeyabalan, 2013)
Leading cause of worldwide pregnancy-related maternal and neonatal mortality
and morbidity (Park et al., 2015)
Maternal Nutrition - Long Chain Polyunsaturated Fatty Acids
3(Uauy et al., 2001)
LCPUFASources
FetalDevelopment
Retina
PlacentalDevelopment
Maternal Diet
Brain
LCPUFA Transfer
Cycle
Rani et al., 2015 (Book Chapter, CRC Press|Taylor and Francis)
LCPUFA – Biosynthesis
4
OMEGA 3 SERIESOMEGA 6 SERIES
Sprecher’s Pathway
α-linolenic acid(ALA; 18:3)
Stearidonic acid(18:4)
Eicosatetraenoic acid(20:4)
Eicosapentaenoic acid(EPA; 20:5)
Docosahexaenoic acid(DHA; 22:6)
Docosapentaenoic acid(DPA; 22:5)
∆-5 Desaturase
C16 Elongase
C20 Elongase
C20/22 Elongase
β-oxidation
Linoleic acid(LA; 18:2)
γ-linolenic acid(GLA; 18:3)
Dihomo-γ-linolenic acid(DGLA; 20:3)
Arachidonic acid(AA; 20:4)
Tetracosapentaenoicacid (24:5)
Tetracohexaenoic acid (24:6)
Peroxisome
Endoplasmic Reticulum
∆-6 Desaturase
∆-6 Desaturase
ENZYMES
LCPUFA – Transport & Metabolism
Rani et al., 2015 (Book Chapter, CRC Press|Taylor and Francis)5
All these placental studies were done on tissues taken
from maternal side of the placenta
Altered LCPUFA levels in PE placenta (Kulkarni et al, 2011a; Wadhwani et al., 2014)
Presence of desaturases enzymes in normal placenta and its reduced expression
in PE placenta (Wadhwani et al., 2014)
Reduced expression of FATP 1 and FATP 4 in PE placenta (Wadhwani et al., 2014)
Altered maternal and cord blood LCPUFA levels in PE (Mehendale et al., 2008; Wadhwani et al.,
2014)
Negative association of placental DHA with oxidative stress marker
homocysteine in PE (Kulkarni et al., 2011b)
Preeclampsia - Our Earlier Studies
6
• Maternal blood flow is initiated in
periphery and expands
progressively (Jauniaux et al., 1999)
• Concentration gradient of nutrient
from maternal to fetal side (Sala et al.,
1984)
• In the pathological pregnancy blood
flow more in the center than the
periphery (Jauniaux et al., 2000)
Placenta - Regions
7
Hypothesis
8
1. To examine the regional placental fatty acids distribution in normotensive
control and preeclampsia placenta.
2. To study the association of these parameters with birth outcome and maternal
blood pressure.
Objectives
9
The sample size was calculated based on
our earlier study with power of 80% and
type I error of 0.05 (Kulkarni et al., 2011)
Recruitment at Dept. of OBGY, Bharati
Hospital, Pune
Ethical approval from institute ethical
committee
Written informed consent taken
Study Design
10
•Normotensive Control (NC)
69
•Term preeclampsia (TPE)
20
•Preterm preeclampsia (PTPE)
24
INCLUSION & EXCLUSION CRITERIA:Preeclampsia women
Blood Pressure ≥140/90 Proteinuria >1+ or 300mg
Normotensive women
Inclusion criteria:Age: 18-35 yrs
Exclusion criteria:History of non-communicable diseases like diabetes
mellitus, renal diseases, hypertension, cardiovascular diseases, seizure disorder, renal or liver disease etc. Pregnant women with alcohol or drug abuse. Multiple gestations (twins etc.). Bleeding disorders, HIV (Human Immunodeficiency virus) and HBsAG (Hepatitis B) positive
Placental tissues were collected
immediately after delivery
Tissues were washed in 1X PBS (phosphate
buffer saline) and kept at -80oC until
analyzed
Placenta Sampling
11
CM
PM
CF
PF
Cord•C
entral Maternal (CM)
1
•Central Fetal (CF)
2
•Peripheral Maternal (PM)
3
•Peripheral Fetal (PF)
4
Attached to Uterus
Towards Fetus
Fatty Acid Estimation:
Transesterification of cell membrane fraction using methanolic–HCl
NC - normotensive control, TPE - term preeclampsia; PTPE - preterm preeclampsia; BMI - body mass index; Sys BP - systolic blood pressure; Dias BP - diastolic blood pressure; MOD - mode
of delivery; C-section - cesarean delivery; n - number; p<0.05; **p<0.01 as compared with NC, &&p<0.01, &p<0.05 as compared with TPE 14
Maternal & Neonatal Characteristics
One Way ANOVA
10
20
30
40
CM CF PM PF
g/1
00
g fa
tty
ac
ids
AA NC (69) TPE (20) PTPE (24)
CM- central maternal region, CF- central fetal region, PM- peripheral maternal region, PF- peripheral fetal region;*p<0.05 than
NC, @p<0.05 than CM Lower in TPE in CF and in PTPE in PF regions than control
Within control, higher in fetal regions (CF&PF) than CM 15
Regionwise Arachidonic Acid Levels
One Way ANOVA
@
* *
@
30
35
40
45
50
55
CM CF PM PF
g/1
00g
fatt
y ac
ids
NC (69) TPE (20) PTPE (24)
CM- central maternal region, CF- central fetal region, PM- peripheral maternal region, PF- peripheral fetal region;*p<0.05 than
NC, @@p<0.05 than CM, %p<0.05 than PM Lower in PTPE in PF regions than control
Within control, higher in PF than CM and PM 16
Regionwise Omega 6 Fatty Acid Levels
One Way ANOVA
*
@ @
%
0
1
2
3
4
5
CM CF PM PF
g/1
00
g fa
tty
ac
ids
DHA NC (69) TPE (20) PTPE (24)
CM- central maternal region, CF- central fetal region, PM- peripheral maternal region, PF- peripheral fetal region; **p<0.01, *p<0.05 than NC, &p<0.05 than TPE, #p<0.05 than CF
Lower in PTPE in CM, CF and PF regions than control
Within PTPE placenta, lower in CF region than PM region17
Regionwise Docosahexaenoic Acid Levels
One Way ANOVA
&**
&
#
&*
1
2
3
4
5
CM CF PM PF
g/1
00g
fatt
y ac
ids
NC (69) TPE (20) PTPE (24)
CM- central maternal region, CF- central fetal region, PM- peripheral maternal region, PF- peripheral fetal region; **p<0.01, *p<0.05 than NC, &p<0.05, &&p<0.05 than TPE, #p<0.05 than
CF Lower in PTPE in central regions (CM&CF) than control
Within PTPE placenta, lower in CF region than PM region18
Regionwise Omega 3 Fatty Acid Levels
One Way ANOVA
&*
#
&&*
Higher in PTPE than TPE and control in both the central regions (CM&CF)
Within PTPE placenta, lower in both the peripheral regions (PM&PF) than CF 19
Regionwise Omega 6:3 Ratio
One Way ANOVA with LSD
0
15
30
45
60
CM CF PM PF
g/1
00
g fa
tty
ac
ids
n6:n3 NC (69) TPE (20) PTPE (24)
#
*&
##*&&
CM- central maternal region, CF- central fetal region, PM- peripheral maternal region, PF- peripheral fetal region; *p<0.05 as compared with NC, &p<0.05 , &&p<0.01 TPE, #p<0.05
##p<0.01 than CF
**p<0.01, *p<0.05 as compared with NC, @@p<0.01, @p<0.05 as compared with CM, #p<0.05 as compared with CF 20
Regionwise Fatty Acid Levels
One Way ANOVA with LSD
Fatty acids(g/100g FA) Gps Central
Maternal Central Fetal Peripheral Maternal Peripheral Fetal
**p<0.01, *p<0.05 as compared with NC, &&p<0.01, &p<0.05 as compared with TPE in the corresponding region; ωωp<0.01, ωp<0.05 as compared with M, ΨΨp<0.01, Ψp<0.05 as compared
with C
Fatty acids Mean± SD Maternal Fetal Central Peripheral