CHAPTER 8 Preimplantation development
Understanding the spatial and temporal developmental processes that take place within an embryo as it develops from a single cell into a recognizable human is the challenge of embryology. The control of these processes resides within the genome: fundamental questions remain concerning the genes and interactions involved in development.
STAGING OF EMBRYOS
For the purposes of embryological study, prenatal life is divided into an embryonic period and a fetal period. The embryonic period covers the first 8 weeks of development (weeks following ovulation and fertilization resulting in pregnancy). The ages of early human embryos have previously been estimated by comparing their development with that of monkey embryos of known postovulatory ages. Because embryos develop at different rates and attain different final weights and sizes, a classification of human embryos into 23 stages occurring during the first 8 weeks after ovulation was developed most successfully by Streeter (1942), and the task was continued by O’Rahilly & Müller (1987). An embryo was initially staged by comparing its development with that of other embryos. On the basis of correlating particular maternal menstrual histories and the known developmental ages of monkey embryos, growth tables were constructed so that the size of an embryo (specifically, the greatest length) could be used to predict its presumed age in postovulatory days (synonymous to postfertilizational days). O’Rahilly & Müller (2000) emphasize that the stages are based on external and internal morphological criteria and are not founded on length or age. Ultrasonic examination of embryos in vivo has necessitated the revision of some of the ages related to stages, and embryos of stages 6–16 are now thought to be up to 3 to 5 days older than the previously used embryological estimates (O’Rahilly & Müller 1999). Within this staging system, embryonic life commences with fertilization at stage 1; stage 2 encompasses embryos from two cells, through compaction and early segregation, to the appearance of the blastocele. The developmental processes occurring during the first 10 stages of embryonic life are shown in Fig. 8.1.
Much of our knowledge of the early developmental processes is derived from experimental studies on amniote embryos, particularly the chick, mouse and rat. Figure 8.2 shows the comparative timescales of development of these species and human development up to stage 12. The size and age, in postovulatory days, of human development from stage 10 to stage 23 is given in Fig. 8.3.
Information on developmental age after stage 23 (8 weeks postovulation) is shown in Fig. 14.3, where the developmental staging used throughout this text is juxtaposed with the obstetric estimation of gestation that is used clinically. A critique of staging terminology and the hazards of the concurrent use of gestational age and embryonic age is given in Chapter 14; sizes and ages of fetuses towards the end of gestation are illustrated in Fig. 14.7.
FERTILIZATION
Fertilization normally occurs in the ampullary region of the uterine tube, probably within 24 hours of ovulation. Very few spermatozoa reach the ampulla to achieve fertilization. They must undergo capacitation, a process which is still incompletely understood, and which may involve modifications of membrane sterols or surface proteins. They traverse the cumulus oophorus and corona radiata, then bind to specific glycoprotein receptors on the zona pellucida, ZP3 and ZP2. Interaction of ZP3 with the sperm head induces the acrosome reaction, in which fusion of membranes on the sperm head releases enzymes, such as acrosin, which help to digest the zona around the sperm head, allowing the sperm to reach the perivitelline space. In the perivitelline space, the spermatozoon fuses with the oocyte microvilli, possibly via two disintegrin peptides in the sperm head and integrin in the oolemma (Fig. 8.4 and Fig. 8.5A).
The sperm head undergoes its protamine → histone transition as the second polar body is extruded. The two pronuclei grow, move together and condense in preparation for syngamy and cleavage after 24 hours (Fig. 8.5B). Nucleolar rRNA, and perhaps some mRNA, is synthesized in pronuclei. A succeeding series of cleavage divisions produces eight even-sized blastomeres at 2.5 days, when embryonic mRNA is transcribed.