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On the origin of germ cells in higher vertebrates.

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Resumen por el autor, Jean Firket
Escuela M6dica Johns Hopkins
Sobre el origen de las c6lulas germinales de 10s vertebrados
En el testfculo y ovario del pollo existen dos generaciones de
c6lulas germinales: las c6lulas germinales primarias, que aparecen
en estados muy tempranos del desarrollo, antes de formarse la
cresta genital, y las cklulas germinales secundarias, que se derivan
del llamado “ epitelio germinal.” Las primeras c6lulas pueden
transformarse en espermatocitos y ovocitos y aunque degeneran
en su mayor parte no es posible determinar si algunas de ellas
producen c6lulas germinales definitivas, porque en ciertos estados
es imposible distinguirlas de esta tiltima clase de c6lulas. En el
macho de la rata blanca aparecen las mismas dos generaciones,
per0 las c6lulas germinales primarias degeneran antes de alcanzar
el period0 de crecimiento y solamente las c6lulas germinales
secundarias se transforman en las definitivas. La desaparicih
de las c6lulas germinales primarias de 10s mamiferos durante la
ontogen6sis en estados mas tempranos del desarrollo que en las
sves parece indicar que se las debe considerar como cklulas en
“ regresi6n filogen6tica.”
Translation by Jose F. Nonidez
Csrnegie Institution of Washington
Anatomical Laboratory, Johns Hopkins Medical School
The opinion that a continual germinal path exists in all animals
and especially in the higher vertebrates is gradually replacing
the more conservative idea that germ cells are derived only from
Waldeyer’s germinal epithelium. Many investigators now hold
that, in the early stages of the ontogenesis of any species, cells
occur which are absolutely distinct from the soma cells and
which are the only cells capable of giving rise to definitive germ
cells during the later development. These cells are called
primordial germ cells.
Such a continual germinal path, the so-called ‘Keimbahn’ of
German authors, has been described in Ascaris, by Boveri; as
early as the fifth segmentation division, one is able to recognize
one of the blastomeres as being the only progenitor of all future
germ cells. It would be certainly valuable, if all animals could
be shown to have this development in common.
Many embryologists have accepted this theory for higher
vertebrates, but only a few have attempted to prove it; the
principal among these are Rubaschkin and Swift. Everyone
knows that, in the amniotes, primordial germ cells have been
shown to occur in very early stages of ontogenesis before the
differentiation of soma cells, and therefore well before the appearance of the genital ridge. The early history of these elements
has been carefully studied during the past ten years, but the
later history of their evolution, when they are embedded in the
genital gland, is not so clearly settled.
Three opinions regarding the later development of these germ
cells in higher vertebrates are now defended.
1. Some investigators claim that the primordial germ cells
in the genital glands are the only possible germ cells, and that
in accordance with this fact the existence of a ‘continual germinal
path’ is a reality (Rubaschkin and Swift).
2. Others believe that the so-called ‘primordial g e m cells’
are really germ cells, but that most of them degenerate and that
a second generation of germ cells is derived from the so-called
.‘germinal epithelium’ (Waldeyer) or the sex cords which it
produces (Felix, Dustin, Allen, and Firket). These authors
call the germ cells belonging to the first generation ‘primary
germ cells’ V.S. to the germ cells derived from the germinal
epithelium which are called ‘secondary germ cells.’
3. Still others assert that the ‘primordial germ cells’ are not
true germ cells, but are temporary hypertrophied cells which
disappear later and that all definitive germ cells are derived
directly from the germinal epithelium (de Winiwarter et Sainmont, von Berenberg-Gossler).
.During the five years preceding the war, I studied, in the
Department of Anatomy of the University of Liege, the changes
in primary germ cells during the development of the genital
glands in birds. Only one part of this work has been published.1
The second part dealt chiefly with the development of the
chicken’s testis. It was entirely written when the war broke
out,’but because I was on duty in the Belgian army, these last
observations could not be published. The Archives de Biologie,
printed in Brussels and suspended during the war, will publish
my work in 1920.
As regards primary germ cells in the chick, my opinion is as
fo1lows:z They are free cells embedded in the mesenchyme
tissue of the splanchnopleure and of the radix of the mesentery
before the genital ridge appears. In these early stages and in
the first days of the developing genital glands, they are migrating
cells, and their migration is ensured by their own movements
Recherches sur l’organogenese des glandes sexuelles chez les oiseaux. Ch.
I B VI. Arch. de Biol., T. 59, 1914.
* These principal results were published in a preliminary note. Anatomischer
Anzeiger, 1914, Bd. 46, S. 422.
until they are embedded and fixed in the sex cords of the genital
glands either in the medullary and cortical cords of the ovary
or in the sex cords of the testis. Some of them do not reach
the sex gland, but they continue their evolution outside of it,
becoming oocytes or spermatocytes while still embedded in the
mesentery or rete. It seemed to me most important, in order t o
prove their sexual nature, to observe, outside the genital gland,
the transformation of these cells into well-characterized oocytes,
for the oocytes observed inside trhe genital organs can always be
said to be elements derived, in situ, from the germinal epithelium
or the epithelial derivatives. Most of the primary germ cells in
the testis as well as in the ovary subsequently degenerate, and
the great majority of the definitive ova or spermatogonia are
derived from the epithelial organs of the sex glands and must
consequently be called secondary germ cells; nevertheless, there
is no reason why certain of the primary germ cells may not produce some of the definitive ova or spermat,ogonia, as it is impossible, at one stage of the ontogenesis, t o distinguish between
primary and secondary germ cells.
In addition t o the above interpretation of these observations
in the chick, the following hypothesis was derived: primary
germ cells must be considered to be “un rappel phylogenique des
gonocytes ddfinitifs des classes infdrieures notament des cyclostomes et des Acraniens.”
Since this work was concluded, other papers on this subject
have appeared. Another account dealing with the ovary and
the testis of the chick has been written by Swift. Though Swift
confirms most of my observations on the organogenesis of the
indifferent gonad and ovary, he does not agree with me in regard
to the existence of secondary gonocytes. His articles and others,
which have been publi’shed during the war, will be discussed
later in a more complete paper with a fuller review of the literature, where the details of my study on the testis of the albino
rat will be given.
Notwithstanding the last articles which conclude that only
primordial germ cells form definitive sex cells, the evidence does
not seem to me sufficient to establish this opinion. M y own
research, started in 1914 on the testis of albino rats, has reinforced my fornier opinion and brought out a new argument in
favor of the hypothesis previously stated regarding the morphological value of the primary germ cells.
Before relating briefly my observations on albino rats, it is a
pleasure to acknowledge the kindness of the Department of
Anatomy of the Johns Hopkins Medical School and especially
that of Doctor Sabin and Doctor Weed for their good welcome
and the great opportunity for work which Ifound in their
laborat ories.
The material studied consisted of the testis of young albino
Tats of all stages from birth until seven weeks and also of a few
embryonic stages. The organs were fixed in different fixing
fluids, particularly those of Flemming, Meves, Regaud, and
mixture). The three
Bensley (bichromate-osmic-acetic-acid
latter were employed for showing the mitochondria (chondriosomes), because Rubaschkin stated that these methods were
elective for studying the primary germ cells in other species.3
The structure of the foetal sex cord of the testis has been known
for a long time; two kinds of cells have been described-large
and small-their nuclei lying regularly in a single row in the
peripheral portion of the cord. The larger cells are characterized
by their size, their well-outlined cytoplasmic body, and their
clear and round nuclei, while the nuclei of the small cells are
smaller, more deeply stained, and are oval in shape with their
long axes at right angles to the basal membrane.
The occurrence of these two kinds of cells brings up the problem as to whether the larger or the smaller gives rise t o the
future spermatogonia. This question has become still more
interesting since it is evident that the fo&er are not derived from
the latter, as is stated in many text-books and even by recent
investigators (Hoven), but that the largest cells of the sex cord
8 I have used for this work material belonging to the embryological collections
of the Anatomical Department of Liege. First collected by Doctor Duesberg,
afterward by Doctor Hoven, and then by myself; I am still enlarging it, due to
the kindness of Dr. Milton J. Greenman, of The Wistar Institute in Philadelphia.
of the foetal testis are exactly the same as the so-called ‘ primordial or primary germ cells’ which appear in the early stages of
ontogenesis. This has been definitely established by the work
of Rubaschkin on mammals and that of Firket and Swift on
the chick.
The structure of the sex cord of the albino rat, the first day
after birth, is just the same as the typical one described above.
The large cells, which we may now call ‘primary’ germ cells, are
easily observed in sections fixed or stained with various histological methods. In these cells a very striking cytological feature
may be observed; the mitochondria are grouped in a complete
ring surrounding the nuclei, all of them are thick, darkly stained,
and very sharply outlined granules; this aspect of the mitochondrial substance differentiates them sharply from the smaller
cells (ordinarily called indifferent germinative cells), in which
the mitochondria are short undulated filaments. This cytological aspect of mitochondria has been already described in the
primordial germ cells of the guinea-pig by Rubaschkin; he
attached great importance to this latter feature, because he
thought that a granular shape of mitochondria was evidence of
the undifferentiated nature of the cells containing them, in
contrast with the soma cells in which their filament-shaped
mitochondria show their differentiated nature. I have already
discussed in a previous paper that interpretation, and have said
that I could not accept it; however, it is a valuable cytological
method for following these cells in their development.
What is the evolution of these cells in the developing testis
of albino rats?
During the days following birth, the gonad increases in size,
because of the active multiplication of the small epithelial germinative cells of the sex cord. Among them foci of mitosis take
place in which the long axis is most often in a line parallel with
the long axis of the sex cord itself. The primary germ cells
in this stage do not, or at least very infrequently, divide. This
difference in the distribution of the foci of cell division explains
the fact that in earlier stages an average of three or four small
epithelial cells were found to separate the two nearest primary
3 14
germ cells, but that in the five-day-old rats this number has
increased to nine or ten. In the following stages, from the
fifth to the tenth day, this number increases still more rapidly,
according to a new phenomenon of the evolution of the primary
germ cells : during the first five days their relative number seemed
to decrease because they were not dividing while the sex cords
were increasing; after the fifth day their number diminishes
absolutely, but not relatively, because they degenerate.
A special type of their degeneration was striking and frequent,
characterized by a great hypertrophy of the cells, in which
cytoplasm and nucleus seem to be filled with water; the chromatin
is shriveled into four or five irregular blocks staining weakly
and lying next to the nuclear membrane; the mitochondria lose
their sharp outlines and seem to be dissolved in the general
cytoplasm. This type of degeneration seems to be a typical
one in the evolution of primordial germ cells, as has been shown
in the ovary and testis of the chick;4 this may be compared to
the type of degeneration described by Champy as ‘ degenerence
ovif orme.’
I n the eighth-day stage, the ratio of the cells in a sex cord is
one primary germ cell to eighteen small epithelial cells, while in
a rat of ten or eleven days old the primary germ cells become
very rare. In this stage there are only a very few cells which
may represent the remains of the primary germ cells, they
are interspersed in the peripheral portion of the sex cord among
the small epithelial cells, from which they are not easily distinguished, although their protoplasm is more deeply stained,
their nuclei have a more round shape and seem to contain less
chromatin. The number of these cells is so small, two or three
in the whole transverse section of the testis, that we may surely
conclude that, as regards their relation to future spermatogonia,
the, primary germ cells have disappeared entirely in the albino
rat’s testis from the tenth t o the fifteenth day after birth.
A t that time the first spermatogonia appear; they are easily
recognizable by the texture of their nuclei and are very numerous.
4 J. Firket, Recherches sur l’organogenese des glandes sexuelles des oiseaux.
Anat. Anzeiger, Bd. 46, S. 422.
This has been shown very distinctly in the same species by
Hoven. Let us insist that these spermatogonia can only be
derived from the small epithelial cells, as they are at this stage
the only type of cells present in sufficient number in the sex
cord. The spermatogonia must then be called ‘secondary
germ cells.’
It is important t o insist that these results have been obtained
by studying the sections where the choddriosomes were stained
as well as those prepared for the study of nuclear texture. That
mitochondria have a very definite granular shape in the firstday stage has been previously noticed; in the later stages, from
the tenth t o the fifteenth day, no cells containing such mitochondria can be found. All the cells composing the sex cofds
contain mitochondria which are not deeply stained and which
have the shape of short filaments.
The principal conclusion derived in this study of the testes
of young rats is as follows: two generations of germ cells exist
which can very easily be distinguished from each other because
the cells of the second generation (the so-called ‘secondary germ
cells’) only arise when those of the first generation (the so-called
‘primary germ cells’) have disappeared. This is in interesting
contrast with what I have described in the chick, where it is
impossible t o separate the first from the second generation of
germ cells when they are present together.
In general, the primary germ cells in the chick are able t o
develop at least until the period of growth; some of these having
become oocytes and spermatocytes reach the well-characterized
stages of preparation for maturation divisions.
This is not true in the albino rat; no primary germ cells ever
reach the period of growth, all of them degenerating at an earlier
If we take the chick as the avian type and the rat as the
mammalian type, the following conclusion may be drawn: the
primary germ cells disappear in the ontogenesis of mammals
earlier than they do in the ontogenesis of birds, and can therefore be considered as being cells in a ‘phylogenetic regression.
Let us insist, however, that the lack of function or, at the
most, the very low importance of function which the primary
germ cells seem to have in amniotes does not diminish the importance of their morphological nature which is asserted by their
ancestral character.
ALLEN, B. M. 1904 The embryonic development of the ovary and testis of
the mammalia. Am. Jour. Anat., vol. 3, p. 86.
1906 The origin of the sex cells of chrysemys. Anat. Anzeiger, Bd. 29.
1914 Ueber Herkunft und Wesen der sogenannten
primiiren Urgeschlechtszellen der Amnioten. Anat. Anzeiger, Bd. 47,
S. 241.
1912 Die Urgeschlechtszellen des Huhnerembryos am 3. und 4. Bebrutungstage. Arch. f. mikr. Anat., Bd. 81. S. 24, Abt. 11.
DUSTIN,A. P. 1910 L’Origine e t l’evolution des gonocytes chez les reptiles.
Arch. de Biol., T. 25, p. 411.
FELIX1906 Die Entwickelung der Keimdrusen. Hertwig’s Handbuch.
FIRKET,JEAN1914 Recherche5 sur l’organogenese des glandes sexuelles des
oiseaux. Arch. de Biol., T. 29, e t Anat. Anzeiger, Bd. 46, S. 413.
JORDAN, H. E. 1917 Embryonic history of the germ cells of the loggerhead
turtle (Caretta caretta). CarnegiePublication 251, vol. 11, pp. 313-344.
F. P. 1916 .Some results and possibilities of embryonic castration.
Anat. Rec., vol. 11, p. 251.
W. 1910 Chondriosomen und Differenzierungsprozesse bei
Saugetier embryonen. Anat. Hefte, Bd. 41, 8. 399.
1912 Zur Lehre von der Keimbahn bei Saugetieren. Anat. Hefte,
Bd. 46.
SWIFT, C. H. 1914 Origin and early history of the primordial germ cells in
the chick. Am. Jour. Anat., vol. 15, p. 483.
1915 Origin of the definitive sex cells in the female chick and their
relation t o the primordial germ cells. Am. Jour. Anat., vol. 18, p. 441.
1916 Origin of the sex cords and definitive spermatogonia in the male
chick. Am. Jour. Anat., vol. 20, p. 375.
VON WINIWARTER,H., AND G. SAINMONT1909 Nouvelles recherches 8ur
l’ovogenese e t l’organogenese de I’ovaire des Mammiferes. Arch.
de Biologie, T. 24, p. 1.
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