Endometrial Cups | |
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Anatomical terminology |
Endometrial cups form during pregnancy in mares and are the source of equine chorionic gonadotropin (eCG) and a placenta-associated structure, which is derived from the fetus. Their purpose is to increase the immunological tolerance of the mare in order to protect the developing foal.
Endometrial cups are unique to animals in the horse family, and so named because of their concave shape. [1] They are a placenta-associated structure, [2] found in the uterine wall of a mare from about 38 to 150 days into a pregnancy. After about 70 days, they begin to regress, [3] and are eventually destroyed by the immune system. [2] They begin to develop at approximately 25 days of pregnancy, deriving from the chorionic girdle. At approximately 36–38 days of pregnancy, the cells that will become the endometrial cup begin to burrow into the endometrial tissue, through the basement membrane, and into the uterine stroma. Their invasion of the uterine stroma begins the cells' maturation process, which takes 2–3 days. Endometrial cups can be circular, U-shaped, or ribbonlike and are pale compared to the rest of the endometrial tissue. They can range in size from 1 cm to 10 cm in diameter at the widest point. [2] They resemble ulcers in form, and when examined under a microscope have large epithelioid decidual-like cells and large nucleoli. [3]
They produce high concentrations of equine chorionic gonadotropin (eCG), also called pregnant mare's serum gonadotropin, in the bloodstream of pregnant mares. eCG is actually an equine luteinizing hormone. [2] Endometrial cups behave somewhat like cells from metastatic tumors, in that they leave the placenta and migrate into the uterus. Their purpose appears to be to work with other placental cells to control the expression of histocompatibility genes so that the developing fetus is not destroyed by the mare's immune system. [1]
Similar types of cells that invade the placenta have been described in humans. The purpose of these cells In both humans and horses is believed to be to interact with the mother's immune system and increase maternal immunological tolerance of the developing fetus. [1]
Mature endometrial cup cells appear rounded and secrete eCG; all but a few cells have two nuclei. As the mare's immune system begins to react to the presence of the pregnancy, histological changes are visible. First, as the endometrial cup grows and develops, maternal white blood cells, including T cells, B cells, and macrophages, mass in the uterine stroma. They begin to destroy the cup around days 70-80 of pregnancy, and it is completely destroyed by 100–140 days, at which point it naturally separates from the endometrium. [2]
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 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.
In mammals, pregnancy is the period of reproduction during which a female carries one or more live offspring from implantation in the uterus through gestation. It begins when a fertilized zygote implants in the female's uterus, and ends once it leaves the uterus.
The placenta is a temporary 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 baby 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.
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo, which eventually forms the placenta after implantation. The presence of hCG is detected in some pregnancy tests. Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages.
The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It develops from an outer fold on the surface of the yolk sac, which lies outside the zona pellucida, known as the vitelline membrane in other animals. In insects it is developed by the follicle cells while the egg is in the ovary.
The blastocyst is a structure formed in the early development of mammals. It possesses an inner cell mass (ICM) which subsequently forms the embryo. The outer layer of the blastocyst consists of cells collectively called the trophoblast. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. The trophoblast gives rise to the placenta. The name "blastocyst" arises from the Greek βλαστός blastos and κύστις kystis. In other animals this is called a blastula.
Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia. Gestational hypertension is defined as having a blood pressure greater than 140/90 on two occasions at least 6 hours apart.
Luteolysis is the structural and functional degradation of the corpus luteum (CL), which occurs at the end of the luteal phase of both the estrous and menstrual cycles in the absence of pregnancy.
The decidua is the modified mucosal lining of the uterus that forms in preparation for pregnancy. It is formed in a process called decidualization under the influence of progesterone. Endometrial cells become highly characteristic. The decidua forms the maternal part of the placenta and remains for the duration of the pregnancy. It is shed off during childbirth—hence why the term is used, "decidua" having the meaning of falling away, as in the word deciduous.
Syncytiotrophoblast is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother. It is a multi-nucleate, terminally differentiated syncytium, extending to 13 cm.
In biology, 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.
"Cytotrophoblast" is the name given to both the inner layer of the trophoblast or the cells that there live. It is interior to the syncytiotrophoblast and external to the wall of the blastocyst in a developing embryo.
In humans, implantation is the stage of human reproduction at which the embryo adheres to the wall of the uterus. At this stage of prenatal development, the conceptus is called a blastocyst. Once this adhesion is successful, the female is considered to be pregnant and the embryo will receive oxygen and nutrients from the mother in order to grow.
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 the third phase of birth.
In the placenta, the intervillous space is the space between chorionic villi, and contains maternal blood.
Equine chorionic gonadotropin is a gonadotropic hormone produced in the chorion of pregnant mares. Previously referred to as pregnant mare's serum gonadotropin (PMSG), the hormone is commonly used in concert with progestogen to induce ovulation in livestock prior to artificial insemination.
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.
Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus during embryogenesis and the mother, including human chorionic gonadotropin (hCG) and progesterone (P4).
Preimplantation factor, sometimes called PreImplantation Factor or simply PIF, is a peptide secreted by trophoblast cells prior to placenta formation in early embryonic development. Human embryos begin to express PIF at the 2-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 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.