Embryogenesis is a very complex system with a slim chance of achieving infant life. Statistical analysis shows that out of 100 oocytes in the presence of sperm, “84 are fertilized, 69 are implanted, a week later 42 are still alive, 37 survive to the sixth week or pregnancy, and only 31 survive to birth.”^[1] In over half of these instances, the cause for zygote death and miscarriage are due to chromosomal abnormalities. Furthermore, many complex cellular steps conducted during pregnancy have to be carried out perfectly to ensure a healthy infant.

After implantation, the inner cell mass of the blastocyst that will become the embryo differentiates into two layers: the epiblast and the hypoblast. The epiblast then gastrulates into three germ layers: the ectoderm, mesoderm, and endoderm, and develops the embryo. At the same time, the hypoblast will form the extra-embryonic membranes: the yolk sac, amnion, and allantois.

Throughout fetal growth, many terms correlate to the cell division and the formation of the epiblast. Following the initial two weeks of development, the term “pre-embryo” is used to refer to the developing structure.  From three to eight weeks post-fertilization, the pre-embryonic cells become distinct and become the “embryo”.  Subsequently, from eight weeks post-fertilization until birth, the developing organism is referred to as the “fetus.”

During early development, cells in the embryo go through a process of differentiation, which involves becoming specialized to perform specific functions. The position of a given cell relative to others can play a crucial role in determining its fate or the specific genes it will express. This concept is known as spatial patterning, or positional information, and implies that the location of a cell within the developing embryo influences the genes it activates and the type of cell it will become.

In addition to the differentiation of various cell types, many essential structures and organs form to support the growing embryo and fetus, including the placenta, umbilical cord and amniotic fluid. As the embryo develops into a fetus, these supportive structures become increasingly important for the well-being of the growing fetus. They play critical roles in ensuring that the fetus receives the necessary nutrients, oxygen, and protection for healthy development. The placenta, umbilical cord, and amniotic fluid are intricately linked in their functions, forming a nurturing environment for the fetus throughout pregnancy.

Morphogenesis

Morphogenesis refers to the shaping and structuring of an organism’s form. It encompasses a series of intricate processes responsible for the emergence of the body’s diverse systems and organs. This developmental journey is a continuous maturation, with all systems and organs initiating their formation in the early stages of pregnancy, primarily within the first eight weeks of gestation, and their progression continues throughout the gestational period. This gradual maturation prepares the fetus for its eventual transition to life outside the womb. Three critical organs that undergo development and determine the potential for fetal survival and health are the heart, lungs, and nervous system. Their maturation and functions are discussed below.

The cardiovascular system, including the heart, is one of the earliest functional systems to develop, with the sound of the heartbeat becoming audible as early as five weeks through vaginal probe or by normal stethoscope at week twelve.

Lung maturity is a critical aspect of fetal development and occurs toward the end of pregnancy, with the proper production of surfactant, a substance produced by special cells in developing fetal lungs. Surfactant plays a crucial role in reducing surface tension in the alveoli (tiny air sacs in the lungs). The maturation of the lungs refers to the readiness of a fetus’s lungs to function effectively in supporting respiration once the infant is born.

The formation of the nervous system, including the central nervous system (CNS) and peripheral nervous system (PNS), begins very early in embryonic development. The neural tube, which eventually becomes the brain and spinal cord, forms as others during the first eight weeks after conception. Fat deposition and myelin formation occur later in fetal development, typically in the third trimester. Myelin is a fatty substance that surrounds nerve fibers and plays a crucial role in the rapid transmission of nerve impulses. This process continues throughout pregnancy and even after birth.

Clinical Correlation

Preterm or Premature Infants

Infants who are born before they have reached full term are at higher risk for various complications because some of their organs and systems may not have fully matured.  For example, the risk of respiratory distress in premature infants is a significant concern because the lungs typically require the last few weeks of pregnancy to develop fully and become fully functional at birth.

Medical professionals closely monitor lung maturity, especially when managing pregnancies that might be at risk for preterm birth. When necessary, interventions may be taken to support lung development, including the administration of corticosteroids to stimulate surfactant production in the lungs and improve lung maturity.

Developmental Milestones

Uncontrolled urination or defecation in a newborn, often referred to as “involuntary voiding” or “involuntary bowel movements,” is indeed a common occurrence. This is primarily due to the immaturity of the nervous system and the myelin sheath at birth.

As the nervous system and myelin sheath continue to mature after birth, infants gradually gain control over these functions. By the age of 2 or 3, most children have developed the ability to voluntarily control urination and bowel movements and have achieved toilet training milestones.

Reproductive System Development

The reproductive system is one of the few systems that matures differently based on the sex of embryos. Sex determination is completed at fertilization. It is well known that females have two X chromosomes, while males have one X and one Y. Since all eggs carry X chromosomes, the determination of sex is reliant on the sperm’s contribution. If the sperm has the Y chromosome, the SRY gene is activated, which initiates the expression of the Testis-Determining Factor (TDF) and leads to the development of the testes. Nevertheless, it is important to note that it takes time for the gonads to differentiate into their final form.

Internal and External Genitalia Differentiation

At week five of development, a paired bulge is present near the midline at the back of the abdominal cavity. These are the genital ridges and are indifferent in males and females. Germ cells from the yolk sac will then migrate toward the genital ridges. Only a week later, indifferent accessory ducts are present. These are the paramesonephric and mesonephric ducts. It is important to note that external genitalia of the different genders also arise from the same structures: the genital tubercle, urogenital folds, and labioscrotal swellings.

At week seven, male structures begin to develop. Primordial germ cells that are XY develop the testis, which secrete testosterone. In males, the paramesonephric ducts degenerate, and the mesonephric ducts develop the accessory ducts and glands of the reproductive system. Until two months before birth, the testes are located in the pelvic cavity. Once stimulated by testosterone the testes then descend into the scrotum. The scrotum is an external structure developed from labioscrotal swelling due to testosterone influence. This hormone also causes the genital tubercle to enlarge, forming the penis and the urogenital fold to form the ventral aspect of the penis.

At week eight, female structures begin to develop. Primordial germ cells that are XX develop the ovaries that eventually descend into the pelvic cavity to be stopped by the broad ligament at the pelvic brim. Degeneration of the mesonephric ducts occurs, and the paramesonephric ducts develop into the oviduct and female genital tract. In the absence of testosterone, the genital tubercle develops into the clitoris, the urethral groove remains open to develop into the vestibule, the urogenital fold becomes the labia minora, and the labioscrotal swellings form into the labia majora.