Fertilization is a complex process that involves the recombination of genetic material and the initiation of embryonic development. Successful fertilization occurs through several steps:

Step 1: The sperm penetrates the expanded cumulus by using a membrane hyaluronidase, PH-20, to digest the extracellular matrix.

Step 2: The sperm then penetrates the zona pellucida by binding to the zona protein ZP3. This binding triggers the release of acrosomal enzymes, known as the acrosomal reaction. The sperm also binds to another zona protein, ZP2, as it swims through the digested zona pellucida.

Step 3: Fusion of the sperm and egg membranes takes place.

Step 4: A calcium signaling cascade occurs.

Step 5: The signaling cascade activates the exocytosis of cortical granules, which are enzyme-filled vesicles located in the outermost region of the unfertilized egg. These enzymes modify ZP2 and ZP3 of the zona pellucida, preventing further binding of acrosome-reacted sperm and capacitated acrosome-intact sperm. This helps ensure that only one sperm usually enters the egg to prevent polyspermy.

Step 6: The entire sperm enters the egg during fusion. The flagellum and mitochondria disintegrate, resulting in most of the mitochondrial DNA being derived from the mother. Inside the egg, the sperm DNA decondenses and a pronucleus forms around it. The egg completes the second meiotic division and releases a large amount of calcium. This calcium release is followed by smaller calcium oscillations that last for hours, "waking up" the metabolically quiescent egg and allowing it to resume meiosis and begin embryonic development. This process is known as egg activation.

The activated egg completes the second meiotic division, forming a pronucleus around the female chromosomes. A centrosome contributed by the sperm becomes a microtubule organizing center, extending microtubules until they contact the female pronucleus. The male and female DNA replicate as the two pronuclei are pulled together. Once the pronuclei contact each other, the nuclear membranes break down, the chromosomes align on a common metaphase plate, and the first cleavage occurs.

Fertilization usually occurs on day 16 to 17 of the menstrual cycle, with implantation occurring approximately 6 days later.
Fertilization accomplishes both recombination of genetic material to form a new genetically distinct organism and initiation of events that begin embryonic development. Several steps must occur to achieve successful (unassisted) fertilization (Fig. 44.31 3,4 ˜Ca++ Zona Egg plasma pellucida ZP2 membrane 3 • Fig. 44.31 Events involved in fertilization (see text for details). (Modified from White BA, Porterfield SP. Endocrine Physiology. 4th ed. Philadelphia: Mosby; 2013.)
Step 1: Penetration of the expanded cumulus by the sperm. This involves digestion of the extracellular matrix of the cumulus by a membrane hyaluronidase, PH-20.
Step 2: Penetration of the zona pellucida by the sperm. This involves binding of the sperm to the zona protein ZP3 (step 2a), which induces release of acrosomal enzymes (called the acrosomal reaction (step 2b). The sperm secondarily bind to another zona protein, ZP2 (step 2c), as the zona pellucida is digested and the sperm swims through to the egg (step 2d).
Step 3: Fusion of the sperm and egg membrane takes place.
Step 4: A Ca++ signaling cascade (see occurs.
Step 5: The signaling cascade activates the exocytosis of enzyme-filled vesicles called cortical granules that reside in the outermost, or cortical, region of the unfertilized egg. The enzymes contained in the cortical granules are released to the outside of the egg upon exocytosis. These enzymes modify both ZP2 and ZP3 of the zona pellucida such that ZP2 can no longer bind acrosomereacted sperm, and ZP3 can no longer bind capacitated acrosome-intact sperm. Thus only one sperm usually enters the egg. Occasionally, more than one sperm does enter the egg. This results in a triploid cell that is unable to develop further. Therefore prevention of polyspermy is critical for normal development of the fertilized egg.
Step 6: The entire sperm enters the egg during fusion. The flagellum and mitochondria disintegrate, so most of the mitochondrial DNA in cells is maternally derived. Once inside the egg, decondensation of the sperm DNA occurs. A membrane called the pronucleus forms around the sperm DNA as the newly activated egg completes the second meiotic division. In mammalian eggs a large initial release of Ca++ is fol lowed by a series of subsequent smaller Ca++ oscillations that can last for hours. A major consequence of this signaling pathway is that it “wakes up” the metabolically quiescent •Fig. 44.32 Overviewofgeneticeventsafterfertilizationuptothefirstembryoniccleavage.(ModifiedfromWhiteBA,PorterfieldSP.Endocrine Physiology. 4thed.Philadelphia:Mosby;2013.) egg so it can resume meiosis and begin embryonic development. This process is called egg activation.
The activated egg completes the second meiotic division as the sperm DNA decondenses and a pronucleus forms around it (
Fig. 44.32). Once the egg has completed meiosis,
CHAPTER 44 The Male and Female Reproductive Systems a pronucleus forms around the female chromosomes as well. A centrosome contributed by the sperm becomes a microtubule organizing center from which microtubules extend until they contact the female pronucleus. The male and female DNA replicate as the two pronuclei are pulled together. Once the pronuclei contact each other, the nuclear membranes break down, the chromosomes align on a common metaphase plate, and the first cleavage occurs.
Fertilization typically occurs on day 16 to 17 of the men strual cycle, and implantation occurs about 6 days later.