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Journal of Dairy, Veterinary & Animal Research

Animal Cloning Drawbacks An-Overview

Abstract Perspective
Cloning is powerful tool for production of genetically identical copies of desired Volume 3 Issue 4 - 2016
donor animal but its success is still questionable. Due to number of factors, many
scientist and common people are against cloning. Up to now it’s consider as
inefficient technique due to high failure of cloned animal growth from gestation
to adulthood. Mostly losses in cloned animals are due to placental abnormalities, Animal Science Department, Guangdong Ocean University,
cardiovascular and respiratory problems. These anomalies are most likely China
due to incorrect epigenetic reprogramming of the donor genome, leading to
inappropriate patterns of gene expression during the development of clone. *Corresponding author: Lilong An, Agricultural collage,
“Large offspring syndrome” is an example of phenotypic anomalies in cloned Animal Science Department, Guangdong Ocean University,
animals. Including this animals’ welfare, health and the significant consequence Zhanjiang, Guangdong, China, Email:
on food safety are reason behind its insufficiency. That’s why still more work
need to understand exact cause of failure during pre- and postnatal development Received: June 07, 2016 | Published: June 23, 2016
of cloned. This article generally focused the problems, due to which cloning is
considered as an inefficient technique.

Keywords: Animal; Cloning; Drawbacks; Food safety; Pregnancy

Introduction development, and is prone to error. There are increasing amounts


of data documenting deviations in epigenetic reprogramming [9].
A sexually Production of genetically identical organisms is
knows as cloning it involves division of a single embryo, either Failure rate of cloning is very high, [10] many cloned embryos
nuclear genes and the small number of mitochondrial genes may develop to preimplantation stage, but the vast majority will
would be “identical”, or it may involve nuclear transfer, in which not result in a viable pregnancy [11]. Despite the use of healthy,
case only the nuclear genes would be “identical”. After struggle fertile synchronous females as recipients it was reported that 50
of many year in 1995 scientists cloned two lambs “Megan and % loss occurred during early first trimester and near about 80 %
Morag” at “Roslin Institute” in Scotland and they were cloned from miscarry by second trimester mostly due to placental abnormalities
cells from an early embryo [1], Although amphibians was already [12]. According to studies in cows and sheep most dramatic
successfully cloned in the 1950s. After that it was reported that a period of fetal loss is at the time of placental attachment [4].
number of lambs had been born by cloning. In February 1997 after After completing gestation cloned animals face greater difficulties
277 attempts a lamb was cloned named as “Dolly “the life span of adjusting to extra uterine life, [13] they look like normal but they
that lamb was quite more than other cloned lambs [2]. Cloning of are genetically different and that differences are due to epigenetic
Dolly heralded the commencement of a new period in agriculture abnormalities acquired during nuclear reprogramming [10].
with the possibility for the protection and rapid multiplication of Many Gestational and neonatal abnormalities are found in cloned
selected genotypes [3]. Up to now many animal animals have been animal, [12] that is may be due irregular expression and likely
cloned by nuclear transfer in mammals like sheep, goat, cattle, incomplete reprogramming of imprinted genes [14]. According
rabbits, mice [4]. Cloning has many application and it make easy to to some other reports the difference is due abnormalities in
rapidly propagate desirable animal stocks, propagating transgenic telomere length, gene expression or methylation patterns [4].
livestock, targeted genetic alterations in domestic animals and
Another problem that is found in Cloned animal is placental
conservation of endangered species [1]. But some of question are
abnormalities. According to many scientists early death of embryo
still un solved like, Ethical and moral issues, and the low success
is due to poor development of placenta. In cloned animal abnormal
rates with somatic cell nuclear transfer due to epigenetic errors
development of allontoic membrane and reduced development of
as a result of inaccurate nuclear programming [5], all the factors
placental blood vessel has been reported, number of placentome
have restricted the satisfactoriness and applicability of cloning in
are quit less in cloned animal [15] and it appears that placental
agriculture.
gas exchange capacity is significantly reduced as late gestation
Cloning limitation is due to complex interaction of many cloned foetuses have been found to be hypoxic [16].
reasons like animal welfare and lack of confidence in long term
Post-natal viability of cloned offspring is lower in cloned
health of cloned animal [6]. During the use of cloning technique
animal but it depends on animal [17]. In post-natal mostly calves
mostly apparently good quality embryos fail to flourish during
showed respiratory problems [18] cardiovascular, skeletal and
pregnancy or following birth [7]. Failure in reprogramming of
central nervous systems problem [7]. The potential for epigenetic
donated nucleus is main cause of flop because of its importance
errors effects on the composition of cloned animals that’s why
in correct pattern of gene expression to occur during subsequent
safety of food products derived had major obstacle in gaining
embryogenesis [8]. This reprogramming must occur within a short
regulatory approval for entry into the food chain.
timeframe, in a different cellular context compared with normal

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J Dairy Vet Anim Res 2016, 3(4): 00087
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Animal Cloning Drawbacks An-Overview ©2016 Ibtisham 2/5

Epigenetic anomalies of pregnancies at day 50 are lost throughout the remainder of


gestation and up to term due to lack of placental vascularisation
Epigenetics means ‘‘the study of mitotically and/or meiotically and attachment sites which are important for nutrient exchange
heritable changes in gene function that cannot be explained by and prevent foetus from hypoxic condition [7]. In third trimester of
changes in DNA sequence [19]. According to theory clone and the cows pregnant with cloned foetuses; some placental abnormalities,
donor animal should have same genome but it’s not likely that such as edema and hydroallantois with occurring chance near
cloned mammals occasionally show developmental anomalies about 45 %, have been also reported [28]. The hydroallantois
due to epigenetic errors [20]. Sometime overgrowth of placenta condition most commonly observe between Days 150 and 180 of
and foetus termed as “large offspring syndrome” [15] other cloned pregnancies [28]. According to research the dysfunction
anomalies include respiratory distress, major cardiovascular and enlargement of placenta can be due to placenta proteins that
abnormalities, and enlargement of organs are commonly seen showed an over expression of TIMP-2 [29] but according to some
in cloned ruminants [21] that’s why applicability of cloning in other it can be due to alteration gene expression in trophoblast of
agriculture is very limited [22]. cloned placentas [30].
The practical outcome is that there are many cloned animals
Difficulties in parturition
that behave and appear normal, while closer investigations have
revealed that even some of these apparently normal animals are At present, cloning generally has low efficiency, as of quite
subtly different from the naturally produced population [23]. In a lot of factors, like reprogramming of nucleus, differentiation
cloning, when somatic cell is transferred from donor to recipient of donor cells, and situation of oocyte [31]. Reprogramming
at that time somatic cell nucleus must be speedily reprogrammed period is the key stage for optimizing cloning [32]. At that time if
to presume its new life of an embryonic cell [24]. In any case if reprogramming not take place properly then it lead to epigenetic
cell unable to reprogram or in complete reprogramming lead to abnormalities and increase the death rate. and somatic cloned
abortive development and possibly non-lethal abnormalities in calves are apparently heavier than embryonic clones [33] that
surviving clones [4]. Some genes are correctly expressed in cloned is also a example of epigenetic abnormalities which increase the
embryos, such as important metabolic enzymes but expression birth complication [13]. Large sized fetus including all neonatal
of some other gene mostly abnormal that affect the future life of abnormalities due to epigenetic error termed as “large calf
clone. In such condition mostly clone apparently experienced a syndrome” [34]. It is common that gestation length in nuclear
normal pregnancy and neonatal period, the outlook for a normal transfer pregnancies is quit prolong, that is due to failure of
life appears good, but placental development and the intrauterine placenta to fetal cortisol near term or to a lack of ACTH release
environment for many clones is suboptimal and this alone may from the fetus [26]. Hormonal imbalance and large size of
impact on their health in later life [25]. fetus are the step toward dystocia, in addition to related post-
partum problems can also have serious negative effects on the
DNA methylation play a important role in gene expression
dam’s health as well as her future production and reproductive
which control animal development [5]. It is reported that
performance in the herd [7].
epigenetic errors primarily in the patterns of DNA methylation
and chromatin organization in cloned embryo [19]. Frequently, Pre and Postnatal viability
the donor cell pattern of DNA methylation is maintained
during pre implantation development [14] which lead to effect Embryo is considered a good quality if number of cell are
reprogramming and that cause abnormal placentation [26]. quite good because it is an important criterion that verify the
Secondary that’s an important reason for the low birth rate [24]. feasibility of the embryo after transfer into a surrogate mother so
the low number of cell in the cloned embryo will be linked with
Placental abnormalities a low percentage of survivability after embryo transfer in several
species [35]. Cloned bovine embryos with a higher percentage of
Placenta is main organ of materno-fetal contact, it plays
apoptotic blastomeres showed lower pregnancy rate after 90 days
a vital role in maintaining pregnancy, and it maintains the
of embryo transfer and subsequently lower calving rate [36].
fetus by satisfying positive nutrient partitionning and critical
endocrine functions. Fetal survival and development during Postnatal viability is markedly lower for many cloned [37]. The
pregnancy depends on appropriate morphological and functional proportion of cloned calves born that are longer-term survivors
development of the placenta. Cloning is always associated with ranges between 47% and 80% [38]. At birth, cloned calves and
placental abnormalities and Indications of placental failure in lambs commonly show signs of a stressful uterine environment;
nuclear transfer pregnancies include anomalies such as large Placental reserve capacity is most likely limited due to inadequate
offspring syndrome, altered placental and fetal membrane development [7]. It is apparent that fetal viability in cloned
proteins, increased placental weight, and placentome enlargement animals varies between experiments and between species, with
and edema in cattle [27]. Hydroallantois has been classified by cloned mice and goats displaying better post natal viability that is
Farin as a Type II abnormal offspring syndrome condition in This may be due to technique, animal strain, or to placental type [26].
pathologic placental condition fetal fluid increases and create Some other cases are also reported about sallow cord of cloned
difficulties in locating the fetus within the uterine horn [27]. calves which can be a potential route of death in postnatal [39].
In cloned calves enlarged umbilical veins and arteries are also
In early pregnancy of cloned animal fetal death rate is
important cause of death in post natal due to sepsis in umbilical
near about 80 % [26] that is mostly due to malfunction and
structures [39].
underdevelopment of placenta [15]. Typically, in cattle, 50-70%

Citation: Ibtisham F, Niu Y, Wang Z, Wu J, Xiao M, et al. (2016) Animal Cloning Drawbacks An-Overview. J Dairy Vet Anim Res 3(4): 00087. DOI:
10.15406/jdvar.2016.03.00087
Copyright:
Animal Cloning Drawbacks An-Overview ©2016 Ibtisham 3/5

According to new research vascular problems are also a cause hydroallantois and fetal hydrops, usually attributed to inadequate
of post-natal death like pulmonary hypertension, lesions, edema placentation [16]. It is also present in literature that loss of
and pleural effusions, in addition to capillary congestion of the clone foetus is also due to hypoxic condition because in cloned
alveolar septa and pulmonary thrombosis causing hemodynamic animal number of placentome is less which able to exchange less
disturbances. These alterations likely inhibited complete alveolar nutrient from dam to foetus and make a unfavourable condition
expansion and explained the pulmonary insufficiency that for development of foetus [15].
contributed to the low post natal survival rate of cloned calves
The high rate of pregnancy loss and neonatal death of cloned
[40]. These vascular developmental problems resulted as the
calves to is due to incomplete nuclear reprogramming; several
primary or key alterations due to epigenetic modifications caused
authors have persuasively confirmed that the donor somatic cell
by cloning.
is reprogrammed such that expression pattern at the blastocyst
Although these particular epigenetic aberrations may be stage is significantly different from that of the somatic cell
minor and not a welfare issue for the animal, they may limit some prior to nuclear transfer [47]. According to Arnold et al. [48]
practical applications of the technology because they decrease the expression of genes critical to normal placental development is
potential uniformity of cloned livestock [41]. A clone phenotype malformed in cloned bovine embryos, and this is likely to cause
well-known diagonally species is confirmation of compromised abnormal trophoblast differentiation and add to pregnancy loss.
immune systems, with thymic aplasia in cloned cattle and lower Even the ongoing offspring have large placentas and increased
antibody production in cloned mice [26]. Compromised immune birth weights, known as large offspring syndrome [14] and some
systems may increase their propensity to infection and disease with a apparently healthy appearance undergo from immune
[9]. dysfunction, leading to increased mortality [24].
In postpartum of Blood samples collected from the cloned According to one report of Marfil et al. [49] in cloned calves
lambs after birth revealed a wide range of abnormalities indicative Respiratory distress 19% and in that condition calves died without
of kidney and liver dysfunction [32]. Further losses throughout any other sign of abnormality. An enlarged umbilical cord 37%,
the post-natal period are mostly due to abnormalities of the hyper/hypothermia 17% and depressed/prolonged recumbency
cardiovascular, skeletal and central nervous systems, umbilical 20% are the most common causes of death between 24 h and 60
and lung infections, along with digestive and kidney disorders [7]. days after birth. Problems that may lower the survival of these
Post natal losses in sheep are greater than cattle [26]. calves at or around the time of birth include increased length of
gestation, severe dystocia, insufficient placental development and
Phenotypes of adult clones function, and failures in metabolic pathways necessary for extra-
If expression patterns genes is abnormal at time of pre- uterine life and some congenital problems such as cerebellar
implantation and in early implantation stages then morphology hypoplasia, respiratory distress and heart enlargement [4].
of clone will be also abnormal [42]. In most of cases clone look It may be normal that clones have a different sensitivity to
like normal and have normal physiology but still many report are stress compared to conservative animals due to it they are more
present that show the abnormalities associated with phenotype prone to pathogens which can also increase the death rate of
[41], like “large offspring syndrome” [9]. That is due to error clones [23]. To prevail over the low efficiency of cloning, various
in gene expression of fetal growth and development [43]. The different method have been tried such as using different types
incidence of these anomalies may vary according to species, of donor cell lines, a variety of culture systems, different fusion
genotype, sex, type of cell or specific aspects of the Nuclear methods, and chemicals [35]. Some of these research efforts
transfer protocol [4]. have led to minor upgrading in the quality of cloned embryos,
High failure rate which is closely related with embryo development and offspring
productivity.
One barrier to the practical use of techniques involving somatic
cell nuclear transfer is the low possibility of cloned embryos; only Ethnics
a few percent of reconstructed oocyte are always able to develop Cloning of animal is the key of development in field of
[43]. Up-to now success rate if cloning of intra species is 1% agriculture and medical but it is acceptable only when the aims
[45] despite use of healthy and synchronize recipient in addition and methods are ethically justified and when it is carried out
to it good quality of embryo used. In most mammalian species, under ethical conditions. Scientists are doing extensive research
assessment of embryo morphology remains the method of in animal cloning but now many ethical issues are raised. The
selection for variety of practicable embryos earlier to transfer. It remarkable inefficiency of cloning poses serious threats to animal
is the most realistic and clinically useful way to assess of embryo welfare [50]. Often, less than one percent of cloning attempts
viability [14]. But still most of cases significant loss of pregnancy will result in a successful birth, and of those that are born, only
is reported in early developmental stages approximately at the a relatively small percentage are healthy enough to live for more
age of 30-90 days of gestation [46] due to failure of placental than a few days or weeks [35]. According to one survey 64% of
membrane and reduce placental vessel development [39]. it is USA people are against the cloning they think that it is against the
reported that Early first trimester pregnancy rates are less than animal welfare that’s why it is morally wrong [51].
1/2 that normally expected, embryonic loss is very high and near
about 80% miscarry by second trimester in addition late gestation During cloning most serious ethical outcome is the pain that
high level of chances to develop placental and fatal abnormalities animal suffer during that process in addition to it cloning also
then normal [7]. The main cause of third trimester losses are effect on other population of animal. Due to it Human beings may

Citation: Ibtisham F, Niu Y, Wang Z, Wu J, Xiao M, et al. (2016) Animal Cloning Drawbacks An-Overview. J Dairy Vet Anim Res 3(4): 00087. DOI:
10.15406/jdvar.2016.03.00087
Copyright:
Animal Cloning Drawbacks An-Overview ©2016 Ibtisham 4/5

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Citation: Ibtisham F, Niu Y, Wang Z, Wu J, Xiao M, et al. (2016) Animal Cloning Drawbacks An-Overview. J Dairy Vet Anim Res 3(4): 00087. DOI:
10.15406/jdvar.2016.03.00087
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Citation: Ibtisham F, Niu Y, Wang Z, Wu J, Xiao M, et al. (2016) Animal Cloning Drawbacks An-Overview. J Dairy Vet Anim Res 3(4): 00087. DOI:
10.15406/jdvar.2016.03.00087

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