Interspecific pregnancy

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Interspecific pregnancy (literally pregnancy between species, also called interspecies pregnancy or xenopregnancy) [1] is the pregnancy involving an embryo or fetus belonging to another species than the carrier. [1] Strictly, it excludes the situation where the fetus is a hybrid 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, where parasite offspring grow inside the organism of another species, not necessarily in the womb.

Contents

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

Gaur at the Bronx Zoo.jpg
Cow female black white.jpg
A gaur (left [note 1] ) embryo may develop to term when gestated by cattle (right [note 1] ), but will have severe intrauterine growth restriction. [2]

Potential applications include carrying human fetuses to term as a potential yet ethically controversial alternative to human surrogate mothers or artificial uteri for gay male couples, [3] 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. [3] For animals, it could be a valuable tool in preservation programs of endangered species, providing a method of ex situ conservation. [4] [5] 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 xenografts rather than allografts, [1] putting a higher demand on gestational immune tolerance in order to avoid an immune reaction toward the fetus. [1] Some mice experiments indicate an imbalance between Th1 and Th2 helper cells with a predominance of Th1 cytokines. [6] However, other mice experiments indicate that an immune response towards xeno-fetuses does not belong to classical cytotoxic T lymphocyte or natural killer cell pathways. [7]

Interspecies compatibility is related to the type of placentation, as mothers of species having the more invasive hemochorial placentation (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, ruminants, horses, whales), where there is no contact between the maternal blood and the fetal chorion. [1] [8]

Other potential hazards include incompatibility of nutrition or other support system. Notably, there is a risk of inappropriate interactions between the trophoblast of the fetus and the endometrium of the mother. [9] For example, the placental glycosylation pattern at the fetomaternal interface should optimally be similar to that of the host species. [10]

Yet, for some species, such as a Bactrian camel embryo inside a dromedary, pregnancy can be carried to term with no other intervention than the embryo transfer. [1] [5] This is possible for gaur embryos inside cattle as well, but with severe intrauterine growth restriction, with uncertainty of how much is caused by the IVF procedure itself, and how much is caused by interspecies incompatibility. [2]

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. [1] [9] Deer mouse embryos survive in the uterus of the white-footed mouse, but the reciprocal transfer fails. [1] [9]

Techniques

Overcoming rejection

Bai yun giant panda.jpg
Black hills cat-tochichi.jpg
Fetuses of the giant panda (left [note 1] ) have been grown in the womb of a cat (right [note 1] ) by intercurrently inserting panda and cat embryos into the cat womb. [11]

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 are aborted when inserted alone into the womb of a goat, but when introduced together with a goat embryo, they may develop to term. [4] This technique has also been used to grow panda fetuses in a cat, but the cat mother died of pneumonia before she completed term. [11] Also, murine embryos of Ryukyu mouse (Mus caroli) will survive to term inside the uterus of a house mouse (Mus musculus) only if enveloped in Mus musculus trophoblast cells. [12] Goat fetuses have likewise been successfully grown in sheep wombs by enveloping the goat inner cell mass in sheep trophoblast. [13] 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. The remaining inner cell mass can be injected into a blastocele of the recipient species to acquire its trophoblastic cells. [14] It has been theorized that the allogeneic component prevents the production of maternal lymphocytes and cytotoxic anti-fetal antibodies, but the mechanism remains uncertain. [9]

On the other hand, immune suppression with ciclosporin has shown no effect for this purpose. Pre-transfer immunization with antigens from the species providing the embryo has promoted more rapid and uniform failure of the interspecies pregnancy in mice, [7] but increased survival in horse-donkey experiments. [15]

A blastocyst, with the inner cell mass, which will become the fetus, colored green. The trophoblast layer, which can be replaced with that of another species, is colored purple. Blastocyst English.svg
A blastocyst, with the inner cell mass, which will become the fetus, colored green. The trophoblast layer, which can be replaced with that of another species, is colored purple.

Embryo creation

Embryos may be created by in vitro fertilization (IVF) with gametes from a male and female of the species to be reproduced. They may also be created by somatic cell nuclear transfer (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. [11] In this experiment, nuclei from cells taken from abdominal muscles of giant pandas were transferred to egg cells of rabbits and, in turn, transferred into the uterus of cat together with cat embryos. Concomitant use of SCNT and interspecific pregnancy has also been speculated to potentially recreate the mammoth 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. [16] [17]

Explanatory notes

  1. 1 2 3 4 Pictured individuals are not the ones used in the studies, but only represent their species.

Related Research Articles

<span class="mw-page-title-main">Endometrium</span> Inner mucous membrane of the mammalian uterus

The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer thickens and then is shed during menstruation in humans and some other mammals, including apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

<span class="mw-page-title-main">Placenta</span> Organ that connects the fetus to the uterine wall

The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

<span class="mw-page-title-main">Blastulation</span> Sphere of cells formed during early embryonic development in animals

Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

<span class="mw-page-title-main">Blastocyst</span> Structure formed around day 5 of mammalian embryonic development

The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. In the late blastocyst the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother.

<span class="mw-page-title-main">Female reproductive system</span> Reproductive system of human females

The female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. The human female reproductive system is immature at birth and develops to maturity at puberty to be able to produce gametes, and to carry a fetus to full term. The internal sex organs are the vagina, uterus, fallopian tubes, and ovaries. The female reproductive tract includes the vagina, uterus, and fallopian tubes and is prone to infections. The vagina allows for sexual intercourse and childbirth, and is connected to the uterus at the cervix. The uterus or womb accommodates the embryo which develops into the fetus. The uterus also produces secretions which help the transit of sperm to the fallopian tubes, where sperm fertilize ova produced by the ovaries. The external sex organs are also known as the genitals and these are the organs of the vulva including the labia, clitoris, and vaginal opening.

<span class="mw-page-title-main">Trophoblast</span> Early embryonic structure that gives rise to the placenta

The trophoblast 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 placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures that do not directly contribute to the embryo. After blastulation, the trophoblast is contiguous with the ectoderm of the embryo and is referred to as the trophectoderm. After the first differentiation, the cells in the human embryo lose their totipotency because they can no longer form a trophoblast. They become pluripotent stem cells.

Ectogenesis is the growth of an organism in an artificial environment outside the body in which it would normally be found, such as the growth of an embryo or fetus outside the mother's body, or the growth of bacteria outside the body of a host. The term was coined by British scientist J.B.S. Haldane in 1924.

<span class="mw-page-title-main">Artificial womb</span> Device that would allow for extracorporeal pregnancy

An artificial womb or artificial uterus is a device that would allow for extracorporeal pregnancy by growing a fetus outside the body of an organism that would normally carry the fetus to term.

Prenatal development includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal development until birth.

<span class="mw-page-title-main">Placentation</span> Formation and structure of the placenta

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 remove waste from the embryo. Placentation is best known in live-bearing mammals (theria), but also occurs in some fish, reptiles, amphibians, a diversity of invertebrates, and flowering plants. In vertebrates, placentas have evolved more than 100 times independently, with the majority of these instances occurring in squamate reptiles.

The Eutherian Fetoembryonic Defense System(eu-FEDS) is a hypothetical model describing a method by which immune systems are capable of recognizing additional states of relatedness like "own species" such as is observed in maternal immune tolerance in pregnancy. The model includes descriptions of the proposed signaling mechanism and several proposed examples of exploitation of this signaling in disease states.

<span class="mw-page-title-main">Implantation (embryology)</span> First stage of pregnancy

Implantation, also known as nidation, is the stage in the embryonic development of mammals in which the blastocyst hatches, attaches, adheres, and invades into the wall of the female's uterus. Implantation is the first stage of gestation, and, when successful, the female is considered to be pregnant. An implanted embryo is detected by the presence of increased levels of human chorionic gonadotropin (hCG) in a pregnancy test. The implanted embryo will receive oxygen and nutrients in order to grow.

<span class="mw-page-title-main">Decidualization</span>

Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes to endometrial stromal cells (ESCs), the presence of decidual white blood cells (leukocytes), and vascular changes to maternal arteries. The sum of these changes results in the endometrium changing into a structure called the decidua. In humans, the decidua is shed during childbirth.

Reproductive immunology refers to a field of medicine that studies interactions between the immune system and components related to the reproductive system, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier. The concept has been used by fertility clinics to explain fertility problems, recurrent miscarriages and pregnancy complications observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is a method for treating many cases of previously "unexplained infertility" or recurrent miscarriage.

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 in the body, as can happen in cases of spontaneous abortion. It is studied within the field of reproductive immunology.

<span class="mw-page-title-main">Placental expulsion</span>

Placental expulsion occurs when the placenta comes out of the birth canal after childbirth. The period from just after the baby is expelled until just after the placenta is expelled is called the third stage of labor.

<span class="mw-page-title-main">Chorionic gonadotropin beta</span> Protein-coding gene in the species Homo sapiens

Choriogonadotropin subunit beta (CG-beta) also known as chorionic gonadotrophin chain beta is a protein that in humans is encoded by the CGB gene.

Menstruation is the shedding of the uterine lining (endometrium). It occurs on a regular basis in uninseminated sexually reproductive-age females of certain mammal species.

<span class="mw-page-title-main">Preimplantation factor</span> Peptide involved in placental development

Preimplantation factor(PIF) is a peptide secreted by trophoblast cells prior to placenta formation in early embryonic development. Human embryos begin to express PIF at the 4-cell stage, with expression increasing by the morula stage and continuing to do so throughout the first trimester. Expression of preimplantation factor in the blastocyst was discovered as an early correlate of the viability of the eventual pregnancy. Preimplantation factor was identified in 1994 by a lymphocyte platelet-binding assay, where it was thought to be an early biomarker of pregnancy. It has a simple primary structure with a short sequence of fifteen amino acids without any known quaternary structure. A synthetic analogue of preimplantation factor (commonly abbreviated in studies as sPIF or PIF*) that has an identical amino acid sequence and mimics the normal biological activity of PIF has been developed and is commonly used in research studies, particularly those that aim to study potential adult therapeutics.

Extravillous trophoblasts(EVTs), are one form of differentiated trophoblast cells of the placenta. They are invasive mesenchymal cells which function to establish critical tissue connection in the developing placental-uterine interface. EVTs derive from progenitor cytotrophoblasts (CYTs), as does the other main trophoblast subtype, syncytiotrophoblast (SYN). They are sometimes called intermediate trophoblast.

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