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Interspecific pregnancy (literally ''pregnancy between species'', also called interspecies pregnancy or xenopregnancy)Page 126 in: is the
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
involving an
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
or
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
belonging to another
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
than the carrier. Strictly, it excludes the situation where the fetus is a
hybrid Hybrid may refer to: Science * Hybrid (biology), an offspring resulting from cross-breeding ** Hybrid grape, grape varieties produced by cross-breeding two ''Vitis'' species ** Hybridity, the property of a hybrid plant which is a union of two dif ...
of the carrier and another species, thereby excluding the possibility that the carrier is the biological mother of the offspring. Strictly, interspecific pregnancy is also distinguished from
endoparasitism Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
, where parasite offspring grow inside the organism of another species, not necessarily in the womb. It has no known natural occurrence, but can be achieved artificially by transfer of embryos of one species into the womb of another.


Potential applications

Potential applications include carrying human fetuses to term as a potential yet ethically controversial alternative to
surrogate mother Surrogacy is an arrangement, often supported by a legal agreement, whereby a woman agrees to delivery/labour for another person or people, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnan ...
s or artificial uteri for gay male couples, mothers with damaged uteri or heterosexual couples that do not want to risk childbirth. It would also provide a sober, drug-free and nonsmoking carrier that is less expensive than human surrogates.Darwin's children
LeVay, Simon. (1997, October 14). from The Free Library. (1997). Retrieved March 6, 2009
For animals, it could be a valuable tool in preservation programs of
endangered species An endangered species is a species that is very likely to become extinct in the near future, either worldwide or in a particular political jurisdiction. Endangered species may be at risk due to factors such as habitat loss, poaching and inv ...
, providing a method of
ex-situ conservation Svalbard GLOBAL SEED BANK, an ''ex situ'' conservation. ''Ex situ'' conservation literally means, "off-site conservation". It is the process of protecting an endangered species, variety or breed, of plant or animal outside its natural habitat; ...
. It could also avail for recreation of extinct species.


Causes of failure

Immunologically, an embryo or fetus of an interspecific pregnancy would be equivalent to
xenograft Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenograf ...
s rather than
allograft Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, o ...
s, putting a higher demand on
gestational immune tolerance Immune tolerance in pregnancy or maternal immune tolerance is the immune tolerance shown towards the fetus and placenta during pregnancy. This tolerance counters the immune response that would normally result in the rejection of something foreign i ...
in order to avoid an immune reaction toward the fetus. Some mice experiments indicate an imbalance between Th1 and Th2 helper cells with a predominance of Th1 cytokines. However, other mice experiments indicate that an immune response towards xeno-fetuses does not belong to classical cytotoxic
T lymphocyte A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
or
natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...
pathways. Interspecies compatibility is related to the type of
placentation Placentation refers to the formation, type and structure, or arrangement of the placenta. The function of placentation is to transfer nutrients, respiratory gases, and water from maternal tissue to a growing embryo, and in some instances to remov ...
, as mothers of species having the more invasive
hemochorial placentation Placentation refers to the formation, type and structure, or arrangement of the placenta. The function of placentation is to transfer nutrients, respiratory gases, and water from maternal tissue to a growing embryo, and in some instances to remov ...
(such as humans) must create a stronger downregulation of maternal immune responses, and are thereby more receptive to fetuses of other species, compared to those with endotheliochorial (e.g. cats and dogs) or epitheliochorial placentation (e.g. pigs,
ruminant Ruminants (suborder Ruminantia) are ungulate, hoofed herbivorous grazing or browsing mammals that are able to acquire nutrients from plant-based food by Enteric fermentation, fermenting it in a specialized stomach prior to digestion, principally ...
s,
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...
s,
whale Whales are a widely distributed and diverse group of fully aquatic placental marine mammals. As an informal and colloquial grouping, they correspond to large members of the infraorder Cetacea, i.e. all cetaceans apart from dolphins and ...
s), where there is no contact between the maternal blood and the fetal chorion. Other potential hazards include incompatibility of nutrition or other support system. Notably, there is a risk of inappropriate interactions between the
trophoblast The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the p ...
of the fetus and the endometrium of the mother. For example, the placental glycosylation pattern at the fetomaternal interface should optimally be similar to that of the host species. Yet, for some species, such as a
Bactrian camel The Bactrian camel (''Camelus bactrianus''), also known as the Mongolian camel or domestic Bactrian camel, is a large even-toed ungulate native to the steppes of Central Asia. It has two humps on its back, in contrast to the single-humped dro ...
embryo inside a
dromedary The dromedary (''Camelus dromedarius'' or ;), also known as the dromedary camel, Arabian camel, or one-humped camel, is a large even-toed ungulate, of the genus ''Camelus'', with one hump on its back. It is the tallest of the three species of ...
, pregnancy can be carried to term with no other intervention than the embryo transfer. This is possible for
gaur The gaur (''Bos gaurus''; ), also known as the Indian bison, is a bovine native to South Asia and Southeast Asia, and has been listed as Vulnerable on the IUCN Red List since 1986. The global population was estimated at a maximum of 21,000 m ...
embryos inside
cattle Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
as well, but with severe
intrauterine growth restriction Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's ...
, with uncertainty of how much is caused by the IVF procedure itself, and how much is caused by interspecies incompatibility. The ability of one species to survive inside the uterus of another species is in many cases unidirectional; that is, pregnancy would not necessarily be successful in the inverse situation where a fetus of the other species would be transferred into the uterus of the first one. For example, horse embryos survive in the donkey uterus, but donkey embryos perish in the uterus of an untreated mare.
Deer mouse ''Peromyscus'' is a genus of rodents. They are commonly referred to as deer mice or deermice, not to be confused with the chevrotain or "mouse deer". They are New World mice only distantly related to the common house and laboratory mouse, ''Mu ...
embryos survive in the uterus of the
white-footed mouse The white-footed mouse (''Peromyscus leucopus'') is a rodent native to North America from Ontario, Quebec, Labrador, and the Maritime Provinces (excluding the island of Newfoundland) to the southwestern United States and Mexico. In the Maritimes, ...
, but the reciprocal transfer fails.


Techniques


Overcoming rejection

Methods to artificially stimulate gestational immune tolerance towards a xeno-fetus include intercurrently introducing a component of a normal allogeneic pregnancy. For example, embryos of the species
Spanish ibex The Iberian ibex (''Capra pyrenaica''), also known as the Spanish ibex, Spanish wild goat, or Iberian wild goat, is a species of ibex endemic to the Iberian Peninsula. Four subspecies have been described; two are now extinct. The Portuguese subs ...
are aborted when inserted alone into the womb of a
goat The goat or domestic goat (''Capra hircus'') is a domesticated species of goat-antelope typically kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the a ...
, but when introduced together with a goat embryo, they may develop to term. This technique has also been used to grow panda fetuses in a cat, but the cat mother died of pneumonia before she completed term. Also,
murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families ex ...
embryos of
Ryukyu mouse The Ryukyu mouse ('Mus caroli'') is a species of rodent in the family Muridae. It is found in Cambodia, China, Indonesia, Japan, Laos, Malaysia, Taiwan, Thailand, and Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the So ...
(''Mus caroli'') will survive to term inside the uterus of a house mouse (''Mus musculus'') only if enveloped in ''Mus musculus'' trophoblast cells. Goat fetuses have likewise been successfully grown in sheep wombs by enveloping the goat inner cell mass in sheep trophoblast. Such envelopment can be created by first isolating the inner cell mass of blastocysts of the species to be reproduced by immunosurgery, wherein the blastocyst is exposed to antibodies toward that species. Because only the outer layer, that is, the trophoblastic cells, are exposed to the antibodies, only these cells will be destroyed by subsequent exposure to
complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...
. The remaining inner cell mass can be injected into a blastocele of the recipient species to acquire its trophoblastic cells. It has been theorized that the allogeneic component prevents the production of maternal lymphocytes and cytotoxic anti-fetal antibodies, but the mechanism remains uncertain. On the other hand,
immune suppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
with
ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
has shown no effect for this purpose. Pre-transfer
immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-se ...
with antigens from the species providing the embryo has promoted more rapid and uniform failure of the interspecies pregnancy in mice, but increased survival in horse-donkey experiments.


Embryo creation

Embryos may be created by
in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
(IVF) with gametes from a male and female of the species to be reproduced. They may also be created by
somatic cell nuclear transfer In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a ...
(SCNT) into an egg cell of another species, creating a cloned embryo that transferred into the uterus of yet another species. This technique was used for the experiment of panda fetuses in a cat mentioned in techniques for overcoming rejection. In this experiment, nuclei from cells taken from
abdominal muscles The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...
of
giant panda The giant panda (''Ailuropoda melanoleuca''), also known as the panda bear (or simply the panda), is a bear species endemic to China. It is characterised by its bold black-and-white coat and rotund body. The name "giant panda" is sometimes us ...
s were transferred to egg cells of
rabbit Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit speci ...
s and, in turn, transferred into the uterus of
cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
together with cat embryos. Concomitant use of SCNT and interspecific pregnancy has also been speculated to potentially recreate the
mammoth A mammoth is any species of the extinct elephantid genus ''Mammuthus'', one of the many genera that make up the order of trunked mammals called proboscideans. The various species of mammoth were commonly equipped with long, curved tusks and, ...
species, for example by taking genetic material from mammoth specimens preserved in permafrost and transferring it into egg cells and subsequently the uterus of an
elephant Elephants are the largest existing land animals. Three living species are currently recognised: the African bush elephant, the African forest elephant, and the Asian elephant. They are the only surviving members of the family Elephantidae an ...
.
/ref>


Explanatory notes


References

{{Reflist Mammalian pregnancy Fertility medicine