Carnegie State 1a = When Sexually Reproduced Human Beings Begin To Exist

Dianne N. Irving
Copyright April 11, 2019
Reproduced with Permission

I. Carnegie Stages of Human Embryonic Development

It has been known and acknowledged for a very long time now that in human sexual reproduction (as distinct from human a-sexual reproduction) a new whole living human organism/human being begins to exist at the beginning of the process of fertilization (not at the end of the process, or after implantation, etc.) at "first contact" of the male sperm with the female oocyte ("egg"), at Stage 1a of the Carnegie Stages of Human Embryonic Development. Thus that is also when that new human being possesses the right to life. This is not a philosophical, religious or political position; it is an objective scientific fact. Repeat: The right to life begins when the human being begins to exist; for sexually reproduced human beings that means at the beginning of the process of fertilization at "first contact" of the male sperm with the female oocyte - Carnegie Stage 1a.

The Carnegie Stages also explain one of the various kinds of human A-SEXUAL reproduction, i.e., Monozygotic (MZ) identical twinning in Stages 2-6; see also Irving article, which explains the long history of the Carnegie Stages (the accurate human embryology known for over 100 years and formally instituted in 1942, how the Stages are updated yearly by an international body, gives the new URLs: "Caution Again: Need to Use Newer URL's for Carnegie Stages for Issues Concerning the Early Human Embryo" (Jan. 1, 2015), at: There are many different kinds of human a-sexual reproduction including various forms of cloning (MZ identical "twinning", nuclear transfer, pronuclear transfer), genetic engineering, synthetic biology, nano technology, gene editing (e.g. CRISPR), etc. The following section consists of direct quotes from Stage 1 of the Carnegie Stages from their website.

II. Stage 1(a,b,c) of the Carnegie Stages (most emphases added for clarification)
Approximately 0.1-0. 15 mm in diameter
Approximately 1 postovulatory day Characteristic feature: unicellularity

(page 9) Embryonic life commences with fertilization, and hence the beginning of that process may be taken as the point de depart of stage 1.

Despite the small size (ca. 0.1 mm) and weight (ca. 0.004 mg) of the organism at fertilization, the embryo is "schon ein individual-spezifischer Mensch" (Blechschmidt, 1972). The philosophical and ethical implications have been discussed briefly by O'Rahilly and Müller (1987).

Fertilization is the procession of events that begins when a spermatozoon makes contact with an oocyte or its investments and ends with the intermingling of maternal and paternal chromosomes at metaphase of the first mitotic division of the zygote (Brackett et al., 1972). Fertilization sensu stricto involves the union of developmentally competent gametes realized in an appropriate environment to result in the formation of a viable embryo capable of normal further development (Tesarík, 1986).

Fertilization requires probably slightly longer than 24 hours in primates (Brackett et al., 1972). In the case of human oocytes fertilized in vitro, pronuclei were formed within 11 hours of insemination (Edwards, 1972).

Given the availability of a mature oocyte (first meiotic division completed) and capacitated spermatozoa (permitting the acrosomal reaction), the criteria for fertilization generally adopted are (1) the presence of two or more polar bodies in the perivitelline space, (2) the presence of two pronuclei within the ooplasm, and (3) the presence of remnants of the flagellum of the fertilizing spermatozoon within the ooplasm (Soupart and Strong, 1974).

Fertilization, which takes place normally in the ampulla of the uterine tube, includes (a) contact of spermatozoa with the zona pellucida of an oocyte, penetration of one or more spermatozoa through the zona pellucida and the ooplasm, swelling of the spermatozoal head and extrusion of the second polar body, (b) the formation of the male and female pronuclei, and (c) the beginning of the first mitotic division, or cleavage, of the zygote. The various details of fertilization, including such matters as capacitation, acrosomal reaction, and activation, are dealt with in special works.

When cortical granules are released, their contents appear to reinforce the structure of the zona pellucida (Sathananthan and Trounson, 1982). This is thought to be the morphological expression of the zonal reaction, and the cortical and zonal reactions may provide a block to polyspermy.

The three phases (a, b, and c) referred to above will be included here under stage 1, the characteristic feature of which is unicellularity. The sequence of events before and during the first three stages is summarized in Table l-l.

The term "ovum," which has been used for such disparate structures as an oocyte and a 3-week embryo, has no scientific usefulness and is not used here. Indeed, strictly speaking, "the existence of the ovum ... is impossible" (Franchi, 1970). The term "egg" is best reserved for a nutritive object frequently seen on the breakfast table.

At ovulation, the oocyte is a large cell surrounded by a thick covering, the zona pellucida, which is believed to be produced (at least largely) by the surrounding follicular cells. Processes of the follicular cells and microvilli of the oocyte both extend into the zona. The diameter of such a mammalian cell, including its zona, ranges from 70 to 190 µm. In the human, the ooplasm measures about 100 µm, and the thickness of the zona ranges from 16 to 18 µm (Allen et al., 1930). Good photomicrographs and electron micrographs of human secondary oocytes are available (e.g., Baca and Zamboni, 1967, figs. 20 to 24; Kennedy and Donahue, 1969). The zona pellucida is covered externally by the corona radiata, which is a loose investment of granulosa cells from the ovarian follicle. On fixation

(page 10) and embedding, the oocyte undergoes shrinkage; this affects the cytoplasm more than the zona, so that a subzonal (or perivitelline) space becomes accentuated. The polar bodies are found within that space. It is said that the first polar body may divide before the second is released, and it has been claimed that each of the three polar bodies is capable of being fertilized. Although it is not unusual for the second polar body to display a nucleus, the chromosomes of the first polar body are isolated and naked (Zamboni, 1971).

It is "likely that no more than one day intervenes between ovulation and fertilization, This time interval may be taken then as the possible error in age of [an] embryo when it is considered the same as ovulatory age" (Rock and Hertig, 1942).

(a) Penetrated oocyte. This term may conveniently be used once a spermatozoon has penetrated the zona pellucida and, strictly, "after gamete plasma membranes have become confluent" (Zamboni et al., 1966). Penetration has been inferred from the presence of spermatozoa in the zona pellucida or in the subzonal space (Edwards, Bavister, and Steptoe, 1969). Moreover, in vitro examples showing portions of spermatozoa within the ooplasm are illustrated by Sathananthan, Trounson, and Wood (1986), in whose work are also

(page 11) detailed views showing the formation of the second polar body.

(b) Ootid The cell characterized by the presence of the male and female pronuclei is termed an ootid (figs, l-l and 1-2). Several examples of human ootids have been described. They are probably about 12-24 hours in age. The diameter, including the zona pellucida, is about 175 µm (Hamilton, 1946; Dickmann et al., 1965), and the diameter of the subzonal space is approximately 140 µm. The cytoplasm of the ootid has a diameter

(page 12) of about 100 µm (Hamilton, 1946; Noyes et al., 1965); each of the pronuclei measures about 30 µm (Zamboni et al., 1966). The various ultrastructural features of the ootid have been described and illustrated (Zamboni et al., 1966; Sathananthan, Trounson, and Wood, 1986).

Although "in most mammalian species, the male pronucleus has been reported to be larger than the female pronucleus," the converse has been found in one human specimen and, in two others, the pronuclei appeared to be of equal size (Zamboni, 1971).

(c) Zygote. The cell that characterizes the last phase of fertilization is elusive. The first cleavage spindle forms rapidly and has been used in identification. Such cells have probably been seen in certain mammals, e.g., the pig, cow, hamster, rat, and mouse.

Pronuclear fusion does not occur. Rather, the two pronuclear envelopes break down ("post-apposition envelope vesiculation," Szabo and O'Day, 1983), and the two groups of chromosomes move together and assume positions on the first cleavage spindle. Thus the zygote lacks a nucleus.

A human embryo "in syngamy just prior to cleavage" has been illustrated by Sathananthan and Trounson (1985, fig. 2). "The chromosomes, some associated in pairs, are located in an agranular zone in the central ooplasm."

In the human, the initial cleavage that heralds the onset of stage 2 occurs in the uterine tube "sometime between twenty-four and thirty hours after [the beginning of] fertilization" (Hertig, 1968).