Implantation

before you start

Throughout this challenge, we will express embryonic and fetal ages in terms of weeks from fertilization, which is commonly called conception. The period of time required for full development of a fetus in utero is referred to as gestation (gestare, to carry or to bear). It can be subdivided into distinct gestational periods. The first 2 weeks of prenatal development are referred to as the pre-embryonic stage. A developing human is referred to as an embryo during weeks 3–8, and a fetus from the ninth week of gestation until birth.

We will cover both the pre-embryonic and embryonic stages of development, which are characterized by cell division, migration, and differentiation. By the end of the embryonic period, all of the organ systems are structured in rudimentary form, although the organs themselves are either nonfunctional or only semi-functional.

1. Pre-Implantation Embryonic Development

Following fertilization, the zygote and its associated membranes, together referred to as the conceptus, continue to be projected toward the uterus by peristalsis and beating cilia of the epithelial cells of the uterine tube. During its journey to the uterus, the zygote undergoes five or six rapid mitotic cell divisions called cleavages. Although each cleavage results in more cells, it does not increase the total volume of the conceptus. Each daughter cell produced by cleavage is called a blastomere (blastos, germ, in the sense of a seed or sprout).

Approximately 3 days after fertilization, a 16-cell conceptus reaches the uterus. The cells that had been loosely grouped are now compacted and look more like a solid mass. The name given to this structure is the morula (morula, little mulberry). Once inside the uterus, the conceptus floats freely for several more days. It continues to divide, creating a ball of approximately 100 cells and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens. The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel. At this developmental stage, the conceptus is referred to as a blastocyst. Within this structure, a group of cells forms into an inner cell mass, which is fated to become the embryo. The cells that form the outer shell are called trophoblasts (trophe, to feed or to nourish). These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between a pregnant person and the developing offspring).

The inner mass of embryonic cells is totipotent during this stage. Recall that you previously learned that totipotent stem cells have the potential to differentiate into any cell type in the human body. Totipotency lasts for only a few days before the cells’ fates are set as being the precursors to a specific lineage of cells.

terms to know

Cleavage

The form of mitotic cell division in which the cell divides but the total volume remains unchanged; this process serves to produce smaller and smaller cells.

Blastomere

The daughter cell of a cleavage.

Morula

A tightly packed sphere of blastomeres that has reached the uterus but has not yet implanted itself.

Blastocoel

A fluid-filled cavity of the blastocyst.

Blastocyst

The term for the conceptus at the developmental stage; it consists of about 100 cells shaped into an inner cell mass that is fated to become the embryo, and an outer trophoblast that is fated to become the associated fetal membranes and placenta.

Inner Cell Mass

A cluster of cells within the blastocyst that is fated to become the embryo.

Trophoblast

A fluid-filled shell of squamous cells destined to become the chorionic villi, placenta, and associated fetal membranes.

Placenta

An organ that forms during pregnancy to nourish the developing fetus; also regulates waste and gas exchange between mother and fetus.

2. Implantation

At the end of the first week, the blastocyst comes in contact with the uterine wall and adheres to it, embedding itself in the uterine lining via the trophoblast cells. Thus begins the process of implantation, which signals the end of the pre-embryonic stage of development. Implantation can be accompanied by minor bleeding. The blastocyst typically implants in the fundus of the uterus or on the posterior wall. However, if the endometrium is not fully developed and ready to receive the blastocyst, the blastocyst will detach and find a better spot. A significant percentage (50%–75%) of blastocysts fail to implant; when this occurs, the blastocyst is shed with the endometrium during menses.

key concept

The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve.

When implantation succeeds and the blastocyst adheres to the endometrium, the superficial cells of the trophoblast fuse, forming the syncytiotrophoblast, which is a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall. In response, the uterine mucosa rebuilds itself and envelops the blastocyst. The trophoblast secretes human chorionic gonadotropin (hCG), a hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogen to suppress menses.

did you know

A missed period (menses) is often the first sign of pregnancy.

These functions of hCG are necessary for creating an environment suitable for the developing embryo. As a result of this increased production, hCG accumulates in the maternal bloodstream and is excreted in the urine. Implantation is complete by the middle of the second week. Just a few days after implantation, the trophoblast has secreted enough hCG for an at-home urine pregnancy test to give a positive result.

Most of the time, an embryo implants within the body of the uterus in a location that can support growth and development. However, in approximately 1%–2% of cases, the embryo implants either outside the uterus (an ectopic pregnancy) or in a region of the uterus that can create complications for the pregnancy. If the embryo implants in the inferior portion of the uterus, the placenta can potentially grow over the opening of the cervix, resulting in a condition called placenta previa.

IN CONTEXT

Embryonic Development Disorders

In the vast majority of ectopic pregnancies, the embryo does not complete its journey to the uterus and implants in the uterine tube. This is referred to as a tubal pregnancy.

However, there are also ovarian ectopic pregnancies (in which the egg never left the ovary) and abdominal ectopic pregnancies (in which an egg was “lost” in the peritoneal cavity outside of the genital organs during the transfer from ovary to uterine tube, or in which an embryo from a tubal pregnancy re-implanted in the peritoneal cavity). Once in the peritoneal cavity, an embryo can implant into any well-vascularized structure—the rectouterine pouch (pouch of Douglas), the mesentery of the intestines, and the greater omentum are some common sites. Some of the various sites of ectopic pregnancies are shown in the images below.

Tubal pregnancies can be caused by scar tissue within the tube following a sexually transmitted bacterial infection. The scar tissue impedes the progress of the embryo into the uterus—in some cases, “snagging” the embryo and in other cases, blocking the tube completely. Approximately one-half of tubal pregnancies resolve spontaneously. Implantation in a uterine tube causes bleeding, which appears to stimulate smooth muscle contractions and expulsion of the embryo. In the remaining cases, medical or surgical intervention is necessary. If an ectopic pregnancy is detected early, the embryo’s development can be arrested by the administration of the cytotoxic drug methotrexate, which inhibits the metabolism of folic acid. If the diagnosis is late and the uterine tube is already ruptured, surgical repair is essential.

Even if the embryo has successfully found its way to the uterus, it does not always implant in an optimal location (the fundus or the posterior wall of the uterus). Placenta previa can result if an embryo implants close to the internal os of the uterus (the internal opening of the cervix). As the fetus grows, the placenta can partially or completely cover the opening of the cervix. Although it occurs in only 0.5% of pregnancies, placenta previa is the leading cause of antepartum hemorrhage (profuse vaginal bleeding after week 24 of pregnancy but prior to childbirth).

terms to know

Implantation

The process by which a blastocyst embeds itself in the uterine endometrium.

Syncytiotrophoblast

Superficial cells of the trophoblast that fuse to form a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall.

Human Chorionic Gonadotropin (hCG)

A hormone that directs the corpus luteum to survive, enlarge, and continue producing progesterone and estrogen to suppress menses and secure an environment suitable for the developing embryo.

Ectopic Pregnancy

Implantation of an embryo outside of the uterus.

Placenta Previa

A condition in which placenta partially or completely covers the opening of the cervix as it grows as a result of low placement of the fetus within the uterus.