Anti-Proliferative Effect of Arsenic, Cadmium and Lead on Human Placental
Cells

 Aftab Ahmad1*, Aamina Shahm2, Abdul Rauf Shakoori1

1School of Biological Sciences, University of the Punjab, Quaid-e-Azam Campus, Lahore. Pakistan.
2Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.

ABSTRACT

Heavy metals are ubiquitously distributed in the environment and can effect human health. Some of
these heavy metals can even cross placenta and cause harm to developing fetus. In the present study
we investigated the anti-proliferative effects of arsenic, cadmium and lead on human placental cells
(PCs). PCs were isolated from placental tissue and cell line was developed. Anti-proliferative effects
of arsenic, cadmium and lead were tested by neutral red uptake assay. Both arsenic and cadmium
proved to be very toxic for PCs. There was marked decrease in cells proliferation when cells were
exposed to metal concentrations for a period of 24 hrs. Reduction in proliferation was recorded on
exposure to leadbut the effect of lead was not as severe as arsenic and cadmium. Arsenic, cadmium
and lead are very toxic for PCs. Proper measures should be taken for the disposal of heavy metals
to protect the environment and humans from exposure.

K e y w o r d s :  P l a c e n t a l  c e l l s ,  H e a v y  m e t a l s ,  P r o l i f e r a t i o n ,  C y t o t o x i c i t y,  M o r p h o l o g y.

INTRODUCTION

During pregnancy placenta,amniotic fluids and fetal
membranes help in growth and development of fetus
by facilitating exchange of gases, nutrients, and
waste products between mother’s circulation and
fetus (Gude et al., 2004; Kippler et al., 2010).
Placenta also prevents pollutants and harmful
substances from entering  into fetus with the help of
macromolecular protein complexes present on its
cell membrane (Osman et al., 2000; Kuhnert et al.,
1987). Placenta is also known as dual marker in case
of certain heavy metals that can effect the fetus
(Iyengar and Rapp, 2001).

Cadmium exposure to human occurs by cigrette
smoking, consumption of polluted food including
cereals, vegetables, nuts, pulses, starchy roots or
potatoes, meat, meat products and contaminated

water (Zenzes et al., 199; Jarup et al., 1998) and
retains in placenta with the help of metalothionin
and doesnot enter in fetus (Brambila et al., 2002).
But cadmium altersplacental transport of calcium
and zinc, causes early decidualization of human
endometrial stroma cells, inhibits trophoblast cell
migration by affecting actin cytoskeletal organization,
reduces leptin synthesis, enhances corticosterone
concentrations and interferes with placental
progesterone production (Ronco et al., 2009; Lin et
al., 1997; Tsutsumi et al., 2009; Alvarez and
Chakraborty, 2011; Stasenko et al., 2010; Kawai et
al., 2002). Endoplasmic reticulum (ER) is essential
for survival and normal functioning of cells and
cadmium also has an effect on ER (Ferri and
Kroemer, 2001; Rao et al., 2004). ER chaperons
causes the folding of nascent proteins but if these
client proteins exceed the chaperons, ER undergoes
stress which in turn reduces the placental development
and fetal growth (Iwawaki et al., 2009; Lian et al.,*Corresponding author: aftabac@yahoo.com

67

Vol 4 (2), July 2013; 67-74



2011; Yung et al., 2008). If the fetus is exposed to
cadmium then it can impair child’s IQ, birth weight,
birth length and head circumference (Tian et al.,
2009; Gonzalez-Cossio et al., 1997; Salpietro et al,
2002; Osman, 2000; Ronco et al, 2009; Gundacker
et al., 2010; Zhu et al, 2010; Lin et al., 2011).
Cadmium toxicity is found to be responsible for this
stress related damage to placenta (Wang et al., 2012).
Since Cadmium has a long half-life in the human
body; the placental burden is affected by the length
of gestation (Kantola et al., 2000).

Arsenic is a metalloid that occurs in environment
both naturally and due to human activities.It is present
in glasses, pesticides, food prservatives and pigments
etc.Human are exposed to arsenic via contaminated
drinking water, rice, other grains and fish etc. (ACSH,
2002). The two oxidation states of inorganic
arsenic,arsenite (AsIII) and arsenate(AsV)can cross
and accumulate in placenta (DeSesso et al., 1998;
Lindgren et al., 1984) upto a level five folds more
than control (Concha et al., 1998a). Its accumulation
can have deleterious vascular effects leading to
placental abnormalities and less flow of blood which
eventually lead to retarded fetal growth (Hopenhayn
et al., 2003). Higher exposure to arsenic causes
increased miscarraige rates, premature deliveries
and lower birth rates(Aschengrau et al., 1989).
If the pregnant lady is exposed to lead contaminated
air or food then lead may cross the placenta to enter
into fetus by passive diffusion (Goyer, 1990) and
accumulates in syncytiotrophoblast cells of placenta
and minimise cytochrome oxidase activity
(Reichrtova et al., 1998), thus may cause
neurodevelopmental disorders and subclinical brain
dysfunction in neonates.

Transportation of  lead and cadmium through placenta
occurs by binding to glutathione (GSH) forming a
complex which is then transferd with the helpof
ABC family such as MRP1, MRP2 and P-
glycoprotein (Gundacker et al., 2010; Thevenod,
2010, UNECB).

In the present study placental cells were used to

investigate the effect of heavy metals such as arsenic,
cadmium and lead on proliferation and morphology
of cells.

MATERIALS AND METHODS

Heavy Metals: Three heavy metals were used in this
study including lead, cadmium and arsenic. Stock
solutions were prepared and filter sterilized with 0.2
µm filter (Orange Scientific). Heavy metals solutions
were stored at room temperature.

Isolation of placental cells (PCs): The placental
tissue was collected after normal delivery. The tissue
was cut into small pieces and added in sterile
phosphate buffer saline (PBS) containing penicillin
and streptomycin (20 ml PBS with 1 ml
penicillin/streptomycin). The samples was
immediately transferred to cell culture lab. The tissue
pieces was washed multiples time with PBS and
chorion layer of placenta was seprated by surgical
knife. The placental tissue was cut into small pieces
and added the piece on tissue culture dish. Let the
tissues to adhere for short time (5min) and completed
medium (DMEM containing glutamine, 10% FBS,
100 U/ml penicillin, and 100 µg/ml streptomycin)
was added. The dish was incubated in CO2 incubator
at37oC with 5% CO2 in humidified environment.
Observe the dish on daily basis to see migrating cells
from tissue.

Cell Culture and CV Staining: When enough cells
migrated out from tissue explants, the explants were
removed and cells were treated with Trypsin-EDTA
(GIBCO, USA). The numbers of cells were counted
and cultured them into new culture flasks under
standard culturing conditions. When cells became
confluent, the cells were stained with crystal violet
(CV) (Sigma). For staining, cells were washed twice
by PBS, stained with 0.5% CV solution for 5-10
min. The stain was removed from plate with dH2O,
until no stain come out. Images were taken by
inverted microscope.

Cytotoxicity assay: PCs were cultured in 75 cm2

68

Vol 4 (2), July 2013; 67-74



69

Vol 4 (2), July 2013; 67-74

tissue culture flask. The cells were incubated for 24
hrs at 37oC in a humidified environment with 5%
CO2 to grow the cells in monolayer. When cells
grew to 90% confluency, they were washed with
PBS, trypsinized with 1X Trypsin-EDTA. The cells
were counted with hemocytometer and 5 x 103 cells
were added in each well of 96 wells plate with a
total volume of 200 µl of complete DMEM medium.
Cells were incubated for 24 hrs at 37 oC in a 5%
CO2 incubator with humidified environment. The
old medium was replaced by 200 µl of fresh medium
containing 0-10 µg/ml cadmium, 0-10 µg/ml arsenic
and 0-100 µg/ml lead respectively and incubated the
plates under the same culture conditions for 24 hrs.
Cytotoxic effects were tested by neutral red uptake
method. Aspirate treatment medium and incubated
cells with Neutral red medium for 3 h at 37oC. Cells
were washed twice with PBS and 150 µl of Neutral
red destain solution was added in each well and put
the plate on shaker at 100 rpm for 10 min. The
supernatant was taken and measured the differential
absorbance at 492nm and 630 nm using ELISA
reader (Humareader plus, HUMAN). All assays were
done in triplicate.

RESULTS

Isolation and Crystal Violet Staining of PCs: When
explant were cultured under standard culture
condition, cells started moving out from explant
after 3 days and in 5 days they covered the surface
of whole plate. Cells were trypsinized and cultured
again. Initially the cells were showing spindle shaped
morphology and also these were very rapidly dividing
cells.

When cells were stained with CV to observe the
morphology of cells after 2nd passage, the cells were
appearing in between the spindle and flattened shape
(Fig. 2).

Cytotoxic effect of arsenic, cadmium and lead on
PCs: PCs were exposed to different concentration
of arsenic, cadmium and lead for 24 hrs but all the
metals have different effect on proliferation of PCs.

The maximum effect was observed by arsenic
followed by cadmium and least was observed in case
of lead. When LC50 was calculated for arsenic and
cadmium, it was 2.52 and 6.2 µg/ml respectively.
The percentage reduction in growth in case of lead
on 24 hrs of exposure was 46% only and LC50 could
not be calculated as lead did not have drastic effects
on proliferation of PCs compared to arsenic and
lead.

DISCUSSION

In the present study we investigated in vitro effect
of three heavy metals on human placental cells. A
significant difference in arsenic content in the human
placenta under exposed (5.9 ng/g) and non-exposed
(2.6ng/g) environmental conditions have been
demonstrated (Iyengar and Rapp, 2001). It was
observed in this study that when PCs were exposed
to arsenic for 24 hrs, its effect was most severe
compared to other heavy metals used in this study

A B

Figure 1. Growth of PCs. (A) The cells are migrating out
from placental explant tissue. (B) Morphology of PCs
after confluent growth. The cells are appearing spindle
shaped and showing similar morphology to that of
mesenchymal stem cells (MSCs).

Figure 2. Morphology of PCs. The morphology of cells
is in between spindle and flattened shape as clearly visible
in both the images after CV staining.



70

Vol 4 (2), July 2013; 67-74

on proliferation as indicated with the measurement

of LC50 which came out to be 2.52µg/ml. When
inside the cells arsenic mainly effects mitochondria,
this result in changes in the trans-membrane potential
and ultimately leads to death of cells (Haga et al.,
2005).

Cadmium also proved to be fatal for PCs but to a
lesser extent than arsenic. On exposing PCs to
cadmium for a period of 24 hrs the LC50 was
calculated to be 6.2µg/ml. According to a studythe
average concentration of cadmium under non-
exposed environmental conditions was4 ng/g, with
a range of 1–6 ng/g based on the wet weight of
placenta (Iyengar and Rapp,2001).The placental
cells causes interruption in cadmium passage either

completelyor partially(Baranowska, 1995; Kuhnert
et al., 1982; Roels et al., 1978; Schramel et al., 1988;
Korpela et al., 1986; Needham et al., 2011) so there
are chances that fetus get exposed to cadmium when
higher level of cadmium is present inside the maternal
body. According to different studies increase in
double-stranded RNA-activated kinase (PKR)-like
ER kinase (PERK)-peIF2a signaling is associated
with decreased cellular proliferation in placenta
(Lian et al., 2011) which is enhanced due to cadmium
exposure (Wang et al., 2012).

Effect of lead was found to be much different than
that of arsenic and cadmium and that could be due
to permeability of lead to PCs. On exposure to lead
for 24 hrs, the percentage reduction in proliferation
of cells was calculated to be 46%.The average
concentration of lead in placental tissue is
approximately 34 ng/g, (normal range5–60 ng/g)
(Iyengar and Rapp, 2001). There does not exist
maternal-fetal barrier for lead and thus level of lead
in fetus blood is nearly equal to maternal blood lead
level (Goyer, 1990), so lead exposure to mother
during fetal development could be very deleterious
for the health of developing fetus especially on
nervous system.

Heavy metals are present in environment and it is
very hard to avoid exposure of heavy metals. The
exposure of heavy metals during pregnancy is great
concern because it is not only dangerous for the life
of mother but it could be lethal for developing fetus.
The present study was conducted to show the anti-
proliferative activity of arsenic, cadmium and lead
on human PCs. It was concluded that among these
heavy metals arsenic is the most toxic heavy metal
for PCs as it had maximum anti-proliferation effect,
followed by cadmium and least anti-proliferative
effect was observed in the case of lead. There is an
alarming increase of heavy metals in environment
in developing countries and it can result in many
abnormalities and malignancies in human and this
is also a serious danger to our future generations.

Figure 3. Graphical representation of effect of arsenic
and cadmium on PCs. There is gradual reduction in
proliferation of cells with increase in concentration of
arsenic and lead but arsenic has more severe effect even
at lower concentration on proliferation of cells as is clearly
shown in figure. There was gradual decrease in
proliferation of cells on increase in concentration of
cadmium.

Figure 4. Graphical representation of effect of lead on
PCs. Lead did not have severe effect on proliferation of
PCs and even at 100 µg/ml concentration there is just
46% reduction in proliferation of cells.



71

Vol 4 (2), July 2013; 67-74

REFERENCES

ACSH. (2002). Arsenic, drinking water, and health:
A position paper of the American Council on Sciences
and Health. American Council on Sciencesand
Health, New York. Regul Toxicol Pharmacol36,
162–174.

Ahmad, S.A., Sayed, M.H., Barua, S., Khan, M.H.,
Faruquee, M.H., Jalil, A., Hadi, S.A. and  Talukder,
H.K. (2001). Arsenic in drinking water and pregnancy
outcomes. Environ Health Perspect109:629–631.

Alvarez, M.M. and Chakraborty, C. (2011). Cadmium
inhibits motility factor-dependent migration of human
trophoblast cells. Toxicol In Vitro25: 1926–1933.

Baranowska, I. (1995). Lead and cadmium in human
placentas and maternal and neonatal blood (in a
heavily polluted area) measured by graphite furnace
atomic absorption spectrometry. Occup Environ Med
52:229–232.

Brambila, E., Liu, J., Morgan, D.L., Beliles, R.P.
and Waalkes, M.P. (2002).Effect of mercury vapor
exposure on metallothionein and glutathione s-
transferase gene expression in the kidney of
nonpregnant, pregnant, and neonatal rats. J Toxicol
Environ Health A65(17):1273-88.

EFSA Panel on Contaminants in the Food Chain
(CONTAM). (2010). Scientific Opinion on Lead in
F o o d ,  E F S A J o u r n a l ,  8 :  1 5 7 0  [ 1 4 7  p p ] .

Fagher, U., Laudanski, T., Schutz, A., Sipowicz, M.
and Akerlund, M. (1993). The relationship between
cadmium and lead burdens and preterm labor. Int J
Gynaecol Obstet 40:109–114.

Gonzalez-Cossio, T., Peterson, K.E. and Sanin, L.H.
(1997). Decrease in birth weight in relation to
maternal bone-lead burden. Pediatrics100: 856–862.

Goyer, R.A. (1990). Transpiacental Transport of
Lead.Environmental Health Perspectives89: 101-

105.

Goyer, R.A. (1990). Transplacental transport of lead.
Environ Health Perspect89: 101-105.

Gude, N.M., Roberts, C.T., Kalionis, B. and King,
R.G. (2004). Growth and function of the normal
human placenta. Thromb Res114: 397-407.

Gundacker, C., Fröhlich, S. and Graf-Rohrmeister,
K. (2010). Perinatal lead and mercury exposure in
Austria. Sci Total Environ408: 5744–5749.

Gundacker, C., Gencik, M. and Hengstschläger, M.
(2010). The relevance of the individual genetic
background for the toxicokinetics of two significant
neurodevelopmental toxicants: mercury and lead.
Mutat Res Rev Mutat705: 130–140.

Haga, N., Fujita, N. and Tsuruo, T. (2005).
Involvement of mitochondrial aggregation in arsenic
trioxide (As2O3)-induced apoptosis in human
glioblastoma cells. Cancer. Sci96(11), 825-833.

Huyck, K.L., Kile, M.L., Mahiuddin, G.,
Quamruzzaman, Q., Rahman, M., Breton, C.V.,
Dobson, C.B., Frelich, J., Hoffman, E., Yousuf, J.,
Afroz, S., Islam, S. and Christiani, D.C. (2007).
Maternal arsenic exposure associated with low birth
weight in Bangladesh. Journal of occupational and
environmental medicine/American College of
Occupational and Environmental Medicine
49:1097–1104.

Iyengar, G.V. and Rapp, A. (2001). Human placenta
as a ‘dual’ biomarker for monitoring fetal and
maternal environment with special reference to
potentially toxic trace elements. Part 3. Toxic trace
elements in placenta and placenta as a biomarker
for theses elements. Sci Total Environ280: 221-238.

Iyengar, G.V. and Rapp, A. (2001). Human placenta
as a ‘dual’ biomarker for monitoring fetal and
maternal environment with special reference to
potentially toxic trace elements. Part 3: Toxic trace



72

Vol 4 (2), July 2013; 67-74

elements in placenta and placenta as a biomarker
for these elements. Science of the Total
Environment280:221–38.

Iyengar, G.V. and Rapp, A. (2001). Human placenta
as a ‘dual’ biomarker for monitoring fetal and
maternal environment with special reference to
potentially toxic trace elements. Part 1: Physiology,
function and sampling of placenta for elemental
characterisation. Science of the Total Environment
280: 195–206.

Järup, L., Berglund, M., Elinder, C.G., Nordberg, G.
and Vahter, M. (1998). Health effects of cadmium
exposure--a review of the literature and a risk
estimate. Scand J Work Environ Health 24 Suppl 1:
1-51.

Kantola, M., Purkunen, R., Kroger, P., Tooming, A.,
Juravskaja, J., Pasanen M, Saarikoskif, S.,
Karp, W.B. and Robertson, A.F. (1977). Correlation
of human placental enzymatic activity with trace
metal concentration in placentas from three
geographical locations. Environ Res 13:470–477.

Kawai, M., Swan, K.F., Green, A.E., Edwards, D.E.,
Anderson, M.B. and Henson, M.C. (2002). Placental
endocrine disruption induced by cadmium: effects
on P450 cholesterol side-chain cleavage and 3beta-
hydroxysteroid dehydrogenase enzymes in cultured
human trophoblasts.Biol Reprod 67(1):178-83.

Kippler, M., Hoque, A.M., Raqib, R., Ohrvik, H.,
Ekström, E.C. and Vahter, M. (2010). Accumulation
of cadmium in humanplacenta interacts with the
transport of micronutrients to the fetus. Toxicol
Lett192: 162-168.

Kippler, M., Hoque, A.M., Raqib, R., Öhrvik, H.,
Ekström, E.C. and Vahter, M. (2010). Accumulation
of cadmium in human placenta interacts with the
transport of micronutrients to the fetus. Toxicol Lett
192:162–168.

Korpela, H., Loueniva, R., Yrjanheikki, E. and

Kauppila, A. (1986). Lead and cadmium
concentrations in maternal and umbilical cord blood,
amniotic fluid, placenta, and amniotic membranes.
A m  J  O b s t e t  G y n e c o l  1 5 5 : 1 0 8 6 – 1 0 8 9 .

Kuhnert, P.M., Kuhnert, B.R., Bottoms, S.F. and
Erhard, P. (1982). Cadmium levels in maternal blood,
fetal cord blood, and placental tissues of pregnant
women who smoke. Am J Obstet Gynecol
142:1021–1025.

Kutlu, T., Karagozler, A.A. and Gozukara, E.M.
(2006). Relationship among placental cadmium,
lead, zinc, and copper levels in smoking pregnant
w o m e n .  B i o l  Tr a c e  E l e m  R e s  11 4 : 7 – 1 7 .

Kwok, R.K., Kaufmann, R.B. and Jakariya, M.
(2006). Arsenic in drinking-water and reproductive
health outcomes: a study of participants in the
Bangladesh Integrated Nutrition Programme. J Health
Popul Nutr24:190–205.

Lin, F.J., Fitzpatrick, J.W., Iannotti, C.A, Martin,
D.S. and Mariani, B.Z.(1997). Tuan RS.Effects of
cadmium on trophoblast calcium transport.Placenta
18(4): 341-56.

Lin. C.M, Doyle. P. and Wang, D. (2011). Does
prenatal cadmium exposure affect fetal and child
growth? Occup Environ Med68: 641–646.

Milton, A.H., Smith, W., Rahman, B., Hasan, Z.,
Kulsum, U., Dear, K., Rakibuddin, M. and Ali, A.
(2005). Chronic arsenic exposure and adverse
pregnancy outcomes in bangladesh. Epidemiology
16:82–86.

Needham LL, Grandjean P, Heinzow B, Jørgensen
PJ, Nielsen F, Patterson DG Jr, et al., 2011. Partition
of environmental chemicals between maternal and
fetal blood and tissues. Environ Sci Technol
45:1121–1126

Osman, K., Akesson, A. and Berglund, M. (2000).
Toxic and essential elements in placentas of swedish



73

Vol 4 (2), July 2013; 67-74

women. Clin Biochem33: 131–138.

Osman. K., Akesson. A., Berglund. M., Bremme.
K., Schütz. A., Ask, K. and Vahter, M. (2000). Toxic
and essential elementsin placentas of Swedish
women. ClinBiochem33: 131-138. Kuhnert, P.M.,
Kuhnert, B.R., Erhard, P., Brashear, W.T., Groh-
Wargo, S.L. and Webster, S. (1987). The effect of
smokingon placental and fetal zinc status. Am J
ObstetGynecol157: 1241-1246.

Rahman, A., Vahter, M., Ekstrom, E.C., Rahman,
M., Golam Mustafa, A.H., Wahed, M.A., Yunus, M.
and Persson, L.A. (2007).  Association of arsenic
exposure during pregnancy with fetal loss and infant
death: a cohort study in Bangladesh. Am J
Epidemiol165:1389–1396.

Reichrtova, E., Dorociak, F. and Palkovicova, L.
(1998). Sites of lead and nickel accumulation in the
placental tissue. Hum Exp Toxicol17: 176-181.

Robert, A. and Goyer. (1990).Transpiacental
Transport of Lead. Environmental Health
Perspectives 89: 101-105.

Roels, H., Hubermont, G., Buchet, J.P. and Lauwerys,
R. (1978). Placental transfer of lead, mercury,
cadmium, and carbon monoxide in women. III.
Factors influencing the accumulation of heavy metals
in the placenta and the relationship between metal
concentration in the placenta and in maternal and
cord blood. Environ Res 16:236–247.

Ronco, A.M., Urrutia, M. and Montenegro, M.
(2009). Cadmium exposure during pregnancy reduces
birth weight and increases maternal and foetal
glucocorticoids. Toxicol Lett 188: 186–19.

Ronco, A.M., Urrutia, M. and Montenegro, M.
(2009). Cadmium exposure during pregnancy reduces
birth weight and increases maternal and foetal
glucocorticoids. Toxicol Lett188: 186–191.

Salpietro, C.D., Gangemi, S. and Minciullo, P.L.

(2002). Cadmium concentration in maternal and cord
blood and infant birth weight: a study on healthy
non-smoking women. J Perinat Med 30: 395–399.

Schramel, P., Hasse, S. and Ovcar-Pavlu, J. (1988).
S e l e n i u m ,  c a d m i u m ,  l e a d ,  a n d  m e r c u r y
concentrations in human breast milk, in placenta,
maternal blood, and the blood of the newborn. Biol
Trace Elem Res 15:111–124.

Scientific Opinion of the Panel on Contaminants in
the Food Chain on a request from the European
Commission on cadmium in food. (2009). EFSA
Journal 980: 1–139.

Stasenko, S., Bradford, E.M., Piasek, M., Henson,
M.C., Varnai, V.M., Jurasovic, J. and Kusec, V.
(2010). Metals in human placenta: focus on the
effects of cadmium on steroid hormones and leptin.J
Appl Toxicol30(3):242-53.

Thévenod, F. (2010). Catch me if you can! Novel
aspects of cadmium transport in mammalian cells.
BioMetals23: 857–875.

Tian, L.L., Zhao, Y.C. and Wang, X.C. (2009). Effects
of gestational cadmium exposure on pregnancy
outcome and development in the offspring at age
4.5 years. Biol Trace Elem Res132: 51–59.

Tsuchiya, H., Mitani, K., Kodama, K. and  Nakata,
T. (1984). Placental transfer of heavy metals in
normal pregnant Japanese women. Arch Environ
Health 39:11–17.

Tsutsumi, R., Hiroi, H., Momoeda, M., Hosokawa,
Y., Nakazawa, F., Yano, T., Tsutsumi, O. and Taketani
,Y. (2009). Induction of early decidualization by
cadmium, a major contaminant of cigarette
s m o k e . F e r t i l  S t e r i l .  9 1 ( 4  S u p p l ) : 1 6 1 4 - 7 .

United Nations Environment Programme Chemicals
Branch. (2010). Final review of scientific information
on cadmium p. 7.



74

Vol 4 (2), July 2013; 67-74

Vahter, M. (2009). Effects of arsenic on maternal
and fetal health. Annu Rev Nutr 29:381–399.

Vartiainen. T. (2000). Accumulation of cadmium,
zinc, and copper in maternal blood and developmental
placental tissue: differences between Finland, Estonia,
and St. Petersburg. Environmental Research83:54–66.

Wang, Z., Wang, H., Xu, ZM., Ji, Y., Chen, Y.,
Zhang, Z., Zhang, C., Xiu-Hong Meng, X., Mei

Zhao, De-Xiang Xu. (2012).Cadmium-induced
teratogenicity: Association with ROS-mediated
endoplasmicreticulum stress in placenta. Toxicology
and Applied Pharmacology 259: 236–247.

Yang, J., Jiang, Z., Wang, Y., Qureshi, I.A. and Wu,
X.D. (1997). Maternal-fetal transfer of metallic
mercury via the placenta and milk. Ann Clin Lab
Sci 27:135–141.

Zenzes, M.T, Krishnan, S., Krishnan, B., Zhang, H.
and Casper, R.F. (1995). Cadmium accumulation in
follicular fluid of women in in vitro fertilization-
embryo transfer is higher in smokers. Fertil Steril
64(3): 599-603.

Zhu, M., Fitzgerald, E.F. and Gelberg, K.H. (2010).
Maternal low-level lead exposure and fetal growth.
E n v i r o n  H e a l t h  P e r s p e c t 11 8 :  1 4 7 1 – 1 4 7 5 .

CA L L  F O R  PA P E R S

Publication is free of cost

t Biochemistry
t Biotechnology
t Botany
t Chemistry
t Environmental Science
t Medical & Health Sciences

t Microbiology
t Molecular Biology
t Pharmacy
t Physics
t Zoology
t Clinical Research

Note:- All manuscripts should be sent by an e-mail to the editor with your mobile number
rads@juw.edu.pk or deanresearch@juw.edu.pk

Our aim is to provide a platform for budding scientists researchers,
research scholars, academicians etc. to present their research findings
in the field of biological and applied sciences.

RADS Journal of Biological Research and Applied Sciences
welcomes the submission of research papers, review articles and short

communications in the following  subject fields: