The Process of Fertilization, Segmentation, and Implantation in Human Reproduction

Fertilization is the process of fusion between male and female gametes, which occurs in the ampullary region of the fallopian tube. In this region, sperm can survive and maintain their fertilization capacity for 1-3 days, while the secondary oocyte dies within 12-24 hours if it remains unfertilized. Sperms deposited in the posterior vaginal fornix are unable to fertilize the oocyte and must migrate towards the oviduct (uterus, fallopian tube) with the help of genital tract muscle contractions.

In the oviduct, sperm undergo a process called "capacitation" and "acrosomal reaction" to acquire their fertilizing capacity. Capacitation, which lasts around 7 hours in humans, involves changes in the sperm as they travel through the female genital tract, including the removal of glycoprotein coatings from the acrosomal region.

The acrosomal reaction takes place near the oocyte and is triggered by substances released by the cumulus cells and the oocyte. This reaction involves the release of acrosomal enzymes, such as hyaluronidase and acrosin, which help the sperm penetrate the corona radiata (the first barrier) and the zona pellucida (the second barrier).

When a sperm encounters an oocyte in the ampulla of the oviduct, it enters the oocyte through the cumulus mass. Upon reaching the zona pellucida surrounding the oocyte, the sperm binds to a specific protein receptor, leading to the release of enzymes from the acrosome that assist in penetrating the zona pellucida. Once the sperm successfully traverses the zona pellucida and reaches the oocyte, the cell membranes of the two cells fuse. This fusion causes the oocyte to release substances that interact with the zona pellucida, making it impenetrable to other sperm and preventing polyspermy.

As soon as the sperm contacts the oocyte's cell membrane (oolemma), fusion occurs between the oolemma and the membrane covering the posterior region of the sperm head. In humans, both the head and tail of the sperm enter the oocyte's cytoplasm, leaving the plasma membrane behind.

Upon entering the oocyte, the sperm triggers three responses:

1. The release of oocyte cortical granules towards the zona pellucida, making it impenetrable to other sperm and preventing polyspermy.
2. Resumption of meiosis II in the oocyte, resulting in the production of the second polar body and completing the oocyte's maturation.
3. Metabolic activation of the egg, where the sperm's nucleus swells and forms the male pronucleus, while the tail degenerates. The male and female pronuclei fuse, resulting in the formation of a diploid zygote.

Fertilization has several consequences, including the restoration of the diploid number of chromosomes, the determination of the new individual's sex, and the initiation of cleavage. The zygote contains a unique combination of chromosomes inherited from both parents, determining the individual's genetic makeup. Additionally, the sex of the embryo is determined by the sperm that fertilizes the ovum, with an X sperm resulting in a female embryo (XX) and a Y sperm resulting in a male embryo (XY). Without fertilization, the oocyte typically degenerates within 24 hours after ovulation.

After pronuclear fusion, the zygote undergoes a series of mitotic cell divisions within 24 hours. These divisions result in the formation of blastomeres, smaller daughter cells. The size of the entire embryo remains the same as it is enclosed within the zona pellucida.

The first division occurs at 30 hours after fertilization, dividing the zygote along a plane perpendicular to the equator and parallel to the polar bodies. Subsequent divisions are slightly asynchronous. The second division, which is mostly complete at 40 hours after fertilization, produces 4 equal blastomeres. By day 3, the embryo consists of 6-12 cells, and by day 4, it has 16-32 cells. At the 32-cell stage, the embryo resembles a small mulberry and is called a morula. The blastomeres will give rise to various structures such as the embryo, annex membranes, placenta, and adjacent structures. These cells follow different developmental pathways, separating and differentiating during the divisions. Starting from the 8-cell stage, the cells begin to flatten and develop a bipolarity (external and internal) with different intercellular adhesion. This reorganization, known as compaction, involves the cytoskeletal activity of the blastomeres. The outer surfaces of the cells become convex, while the inner surfaces become concave.

The appearance of different adhesions between groups of blastomeres leads to the segregation of some cells in the center of the morula and others on the outside. Blastomeres of the IIIrd or IVth generation, which divide earlier, move towards the center to form the inner cell mass called the embryoblast. The peripheral blastomeres form the outer cell mass known as the trophoblast, which is the primary source for placenta formation.

By the 4th day of development, the morula consists of approximately 30 cells that start to absorb fluid. This fluid is absorbed into the intracellular vacuoles and intercellular spaces. The fluid is mainly located between the cells of the inner cell mass due to the development of tight junctions between the cells of the outer cell mass. The hydrostatic pressure increases, forming a cavity called the blastocyst cavity. The embryoblastic cells form a compact mass at one pole of this cavity, while the trophoblast forms a thin epithelium arranged in a single layer. At this stage, the embryo is called a blastocyst. The part of the blastocyst containing the inner cell mass is called the embryonic pole, while the opposite part is called the non-embryonic pole.

The development of the morula takes place between the 3rd and 4th day, after which it reaches the uterus. On the 5th day, the blastocyst emerges from the zona pellucida by creating a hole using enzymes. Once released, it can directly interact with the uterine endometrium.

Upon reaching the uterus, the blastocyst quickly adheres to the uterine epithelium. Around the 6th day, the trophoblastic cells located above the embryonic pole of the blastocyst start to penetrate and insert themselves between the epithelial uterine mucosa. In response to the presence of the blastocyst and progesterone secreted by the corpus luteum, adjacent stromal cells undergo differentiation processes and become metabolically active, secretory cells. These cells are known as decidual cells, and this process is referred to as the decidual reaction.

The implantation area of the uterine wall experiences enlargement of endometrial glands, edema, and increased vascularity. The secretion of decidual cells and endometrial glands contains growth factors and metabolites that support the development of the embryo. The trophoblastic cells secrete proteolytic enzymes that help the blastocyst erode and infiltrate the endometrial cells. The corpus luteum secretes progesterone, which maintains the uterine epithelium and prevents shedding (menstruation). If there is no embryo, the corpus luteum degenerates after approximately 13 days.

If the embryo successfully implants, the trophoblastic cells secrete human chorionic gonadotropin (hCG), which protects the corpus luteum and ensures the maintenance of progesterone levels. The corpus luteum continues to secrete sex steroids until weeks 11-12 of development, at which point the placenta takes over progesterone secretion. The corpus luteum gradually regresses and becomes a corpus albicans.

The uterine wall is composed of three layers: the internal layer known as the endometrium or uterine mucosa, the middle layer called the myometrium or uterine muscle, and the outer layer referred to as the perimetrium.

The uterine endometrium undergoes cyclic changes from puberty to menopause, approximately every 28 days, under the influence of ovarian hormones. These changes occur in three phases during the menstrual cycle:

1. The proliferative or follicular phase starts after the menstrual phase and is driven by estrogens. It coincides with the growth of ovarian follicles.
2. The secretory phase begins around 2-3 days after ovulation and is triggered by progesterone from the corpus luteum. If fertilization does not occur, the endometrium sheds its spongy and compact layers, initiating the menstrual phase. In case of fertilization, the endometrium prepares for implantation. During implantation, the secretory phase of the uterine mucosa is characterized by edema, increased vascularity, spiral arteries, and numerous glands. The endometrium consists of three layers: a superficial compact layer, an intermediate spongy layer, and a basal sublayer.
3. The menstrual phase starts if fertilization does not occur, resulting in the shedding of the compact and spongy layers. The basal layer, which has its own regenerative activity, remains intact and serves as the foundation for the reconstruction of glands and arteries during the proliferative phase.

Attention

Normally, the blastocyst implants in the center of the posterior or anterior wall of the uterine body. However, implantation in abnormal locations can lead to ectopic pregnancies. Ectopic pregnancies occur when the blastocyst implants in the peritoneal cavity, on the surface of the ovary, inside the fallopian tube, or in an abnormal location within the uterus. The epithelium of these abnormal sites responds to the implanted blastocyst by increasing vascularisation and undergoing other changes, allowing the blastocyst to survive and develop for a certain period.

Ectopic pregnancies pose a significant risk to the mother's life, as the blood vessels surrounding the abnormal site can rupture due to the growth of the embryo and placenta. Symptoms of ectopic pregnancy include abdominal pain and vaginal bleeding, often requiring emergency surgery to remove the developing embryo.

References

1. Anatomia Omului, Volumul I: Embriologie; Semestrul I; Prof. univ. dr. med. Andrei Motoc; Editura „Victor Babeș”, Timișoara, 2018

2. Embriologie - Sinteze didactice; Romeo Chiriac, Anca Indrei ;Editura Fundatiei Chemarea, Iasi, 1997

Custom citation style optimized for readability:
Title -> Authors -> Source -> Date

Reset