1. The effect of X-irradiation on the germ cells of the developing chick ovary depends on both the dose administered, and on the age of the embryo at the time of exposure. Germ cells are particularly radiosensitive at 11 days’ incubation; they become less so up to 17 days.

  2. Peak radiosensitivity at 11 days’ incubation coincides with a high mitotic activity of oögonia, but not with its maximal incidence (9th day of incubation). Oögonia undergoing their last (pre-meiotic) mitosis may be particularly radio-sensitive. Oocytes at the leptotene, zygotene and pachytene stages of meiotic prophase apparently become increasingly radioresistant.

  3. X-irradiation induces a slight retardation in the subsequent development of the ovary.

Numerous recent studies have clearly shown that in mammals, the radio-sensitivity of germ cells changes markedly during the course of ovarian development (e.g. Rugh & Jackson, 1958; Russell, Badgett & Saylors, 1960; Beaumont, 1961, 1962). In the rat, for instance, female germ cells undergo two periods of high radiosensitivity : the first at 15 · 5 days post coitum, and the second some 5 days post partum. The first peak is correlated with a high incidence of oögonial mitoses, while the second coincides with the onset of the ‘dictyate’ phase of meiotic prophase (Beaumont, 1961, 1962; cf. Beaumont & Mandl, 1962). Oocytes at the leptotene, zygotene and pachytene stages are relatively radioresistant.

Corresponding observations on oögonia and oöcytes of the developing avian embryo are scanty, and some were made before the advent of accurate dosimetry. Dantschakoff & Lacassagne (1932) claimed that a total dose of 900 r. of X-rays, administered in three sessions (on the 6th, 9th and 12th days of incubation) induced ‘sterility’ by the 17th and 19th days of incubation. In contrast, Glad-stone & Colwell (1933) observed only minor histological changes in the ovaries of chick embryos 2 to 24 hr. after exposure to 4 pastille doses (Sabouraud) of X-rays on the 9th day of incubation (i.e. probably between 1500 and 2000 r.). According to Essenberg & Zikmund (1938), ovarian radiosensitivity is maximal at 5 to 7 days’ incubation; it decreases between the 8th and 12th days, and following irradiation shortly before or after hatching, scarcely any changes could be detected in the ovaries. Warren & Dixon (1949) also postulated that the germ cells of chick embryos become more resistant to ionizing radiations as they mature. Injections of 47 · 5 μC. of 32P into embryos at 4 to 8 days’ incubation destroyed all the germ cells, whereas a dose of 200 μC. given on the 14th day failed to do so. More recently, Moreng & Muller (1962) have shown that, as judged by the rate of egg-laying after the onset of sexual maturity, the ovary of the chick embryo is particularly radiosensitive on the 12th day of incubation.

The process of oogenesis in the chick has recently been re-investigated. Estimates of the population of germ cells, together with a cytological study of their chromosomal configuration, have shown that the process is strikingly similar in birds and mammals. Oögonial mitoses cease at relatively early stages of development, when the majority of germ cells enter the prophase of meiosis (Hughes, 1963; cf. Beaumont & Mandl, 1962; Franchi, Mandl & Zuckerman, 1962).

The present study was undertaken in order to determine the rate of radiation-induced cell-death in obgonia and oocytes of the developing chick; and to correlate the extent of such damage with morphological and cytological changes occurring in the ovary at the time of exposure.

Animals

Fertile eggs (F1 generation White Leghorn × Rhode Island Red) were incubated at 39 · 5°C. and 60 per cent, humidity. Chicks were housed in brooders at 35°C. The room containing the brooders was constantly illuminated, but the chicks were given free access to an area covered by felt which transmitted little or no light.

X-irradiation

In order to determine the position and depth of the ovary at different developmental periods, eggs incubated for 9 to 19 days were candled, and the site of the embryo marked on the egg shell. The eggs were immediately ‘fixed’ by cooling to approximately −12°C. On sectioning the eggs, the distance between the ovary of the embryo and the mark on the shell was found to fluctuate, but the mean depth was ca. 1 cm. This factor was taken into account when calculating the ovarian dose of X-rays.

Eggs were irradiated on the 9th, 11th, 13th, 15th, 17th and 19th days of incubation with doses of 200 and 400 r. A superficial X-ray apparatus was used, fitted with an applicator whose field diameter was 4 cm.; the focal skin distance was 14·5 cm. The egg to be irradiated was placed on a polythene bag filled with water. Fluctuations in temperature were reduced by keeping the water at about 37° C. Bolus bags (containing a mixture of 60 per cent, rice starch and 40 per cent, borax) were placed around the egg so as to obtain maximum backscatter.

The X-ray machine was set at 100 kV. and 5 mA. The dose in air at the end of the applicator was 430 r./min. The absorption at 1 cm. depth was 66 · 5 per cent, of the above, i.e. 286 r./min. The doses of 200 and 400 r. were thus delivered in 42 sec. and 1 min. 24 sec., respectively. In order to minimize variability in the ovarian dose of X-rays, the eggs were candled prior to X-irradiation and the position of the embryo marked on the shell. During exposure, this mark was placed immediately beneath the applicator. After irradiation, the eggs were at once replaced in the incubator.

Autopsy

Experiment I

The chicks were killed at 2 days after hatching by means of chloroform vapour. The left ovaries of female specimens were dissected free from all adjoining tissues before being prepared for histological processing. The left ovaries of two un irradiated chicks, also fixed 2 days after hatching, served as controls.

Experiment II

Embryos were removed from eggs 2 days after irradiation. Chicks irradiated on the 19th day of incubation were allowed to hatch; they were killed 1 day after hatching (i.e. 2 days after irradiation). The left ovaries of all specimens were dissected and fixed. No control specimens were needed in this experiment, since the same stock of birds, conditions of incubation, histological procedures and methods of estimating the population of germ cells were employed in a recent study of unirradiated ovaries (Hughes, 1963).

Histological procedures

Serial sections, 10 μthick, were prepared by the method outlined previously (Hughes, 1963).

Estimation of the population of germ cells

In both Experiments I and II, four specimens were examined for each age group (two irradiated with 200 r.; two with 400 r.). Counts were also made on two unirradiated ovaries added to Experiment I.

Serial sections were examined under a magnification of × 1250, and germ cells situated in the ovarian cortex counted in every 40th section. In order to estimate the total population of germ cells, the counts were simply multiplied by forty (see Hughes, 1963). As in the previous study, care was taken to record only those cells whose nucleus was largely included in the selected section. Since the ‘marker’ used was the nucleus itself, and since the size of the nucleus varies according to the developmental stage of the germ cell, none of the commonly used correction factors was applicable.

In Experiment I, cortical germ cells were classified as normal or ‘degenerating’; in Experiment II, separate records were also kept of mitotically active oögonia at pro-, meta- and anaphase.

Experiment I

Quantitative changes

Table 1 shows the numbers of germ cells in the left ovaries of 2-day-old chicks (hatched) which had been exposed to 200 or 400 r. at 9,11,13,15,17 and 19 days’ incubation. Counts made on two unirradiated specimens of the same age are added for comparison.

TABLE 1.

Numbers of germ cells in 2-day-old chicks after irradiation at 9 to 19 days’ incubation (Experiment I)

Numbers of germ cells in 2-day-old chicks after irradiation at 9 to 19 days’ incubation (Experiment I)
Numbers of germ cells in 2-day-old chicks after irradiation at 9 to 19 days’ incubation (Experiment I)

The results clearly indicate that the population of oocytes in ovaries irradiated during embryonic development depends both on the dose of X-rays administered and on the age of the embryo at the time of exposure. Irradiation on the 9th day of incubation caused a drastic reduction in the total population of germ cells, but maximal depletion occurred after treatment on the 11th day (Table 1; Text-fig. 1). The germ cells become progressively more radioresistant up to the 17th day. For instance, a dose of200 r. given at 11 days’ incubation reduced the total population at 2 days after hatching to ca. 17 per cent, of that of controls; the same treatment given on the 17th or 19th day induced no significant change. A dose of 400 r., however, if administered on the 19th day, decreased the total population to about 71 per cent, of that of control birds, a decrease which exceeds that following the same treatment on the 17th day (Text-fig. 1). In view of the variability between individual observations (see Hughes, 1963), this difference may not be significant.

TEXT-FIG. 1.

The population of germ cells in chicks aged 2 days after hatching, ○ — — — — — following exposure to 200 r. and ○ — ○400 r. at 9 to 19 days’ incubation.

TEXT-FIG. 1.

The population of germ cells in chicks aged 2 days after hatching, ○ — — — — — following exposure to 200 r. and ○ — ○400 r. at 9 to 19 days’ incubation.

The percentage of germ cells classified as ‘degenerating’ was not consistently influenced by irradiation of the embryo (Table 1). It should be noted that the diagnosis is subjective, and small differences are unlikely to be meaningful. Exposure to 400 r. on the 9th day of incubation, however, did cause a considerable increase in the proportion of oocytes at advanced stages of atresia (Table 1).

Qualitative changes

A comparison between normal and irradiated ovaries indicates that radiation-induced histological changes in non-germinal elements are small. Variations in the thickness of the cortex are directly correlated with differences in the population of germ cells. Many irradiated ovaries, however, contain cortical cysts.

Qualitative observations indicate that germ cells in control ovaries are more advanced in their development than are those in irradiated ovaries. This applies particularly to gonads irradiated at early stages of development. Those exposed to 400 r. on the 9th day of incubation, for example, contain very few oocytes at the diplotene stage. Most oocytes are at the zygotene and pachytene stages, while mitotically active oögonia persist at the extremities of the cortex. It should be noted that in unirradiated birds, oogenesis ceases at about the time of hatching (Hughes, 1963). The appearance of degenerating germ cells in irradiated ovaries is very similar to that in controls.

Experiment II

Quantitative changes

Table 2 shows the numbers of germ cells in the left ovaries of chicks removed 2 days after X-irradiation (200 and 400 r. at 9,11,13,15,17 and 19 days’ incubation). The means are summarized in Text-fig. 2. Control values (from Hughes, 1963) are shown in Table 3 for comparison.

TABLE 2.

Numbers of germ cells 2 days after irradiation at 9 to 19 days’ incubation (Experiment IT)

Numbers of germ cells 2 days after irradiation at 9 to 19 days’ incubation (Experiment IT)
Numbers of germ cells 2 days after irradiation at 9 to 19 days’ incubation (Experiment IT)
TABLE 3.

Mean numbers of germ cells in unirradiated ovaries (from Hughes, 1963)

Mean numbers of germ cells in unirradiated ovaries (from Hughes, 1963)
Mean numbers of germ cells in unirradiated ovaries (from Hughes, 1963)
TEXT-FIG. 2.

The population of germ cells 2 days after exposure to ○ — — — — — — ○200 r. and ○ — ○ 400 r. at 9 to 19 days’ incubation. Numbers present in unirradiated chick ovaries (o o) are shown for comparison.

TEXT-FIG. 2.

The population of germ cells 2 days after exposure to ○ — — — — — — ○200 r. and ○ — ○ 400 r. at 9 to 19 days’ incubation. Numbers present in unirradiated chick ovaries (o o) are shown for comparison.

The results of Experiment II confirm that germ cells become increasingly radio resistant after the 13th day of incubation (Table 2; Text-fig. 2). The total numbers of germ cells in irradiated ovaries, expressed as percentages of those in unirradiated specimens, are shown in Text-fig. 3. It is clear that the highest proportion of germ cells is again eliminated following exposure on the 11th day of incubation. A comparison of Text-fig. 1 (autopsy 2 days after hatching) and Text-fig. 3 (autopsy 2 days after irradiation) suggests that such germ cells as degenerate as a result of irradiation are eliminated from the ovary within the first 2 days after exposure.

TEXT-FIG. 3.

The population of germ cells 2 days after exposure to 200 r. (○ —○) and 400 r. (○ — — — — —○) at 9 to 19 days’ incubation, expressed as a percentage of the number normally present in unirradiated 2-day-old chicks.

TEXT-FIG. 3.

The population of germ cells 2 days after exposure to 200 r. (○ —○) and 400 r. (○ — — — — —○) at 9 to 19 days’ incubation, expressed as a percentage of the number normally present in unirradiated 2-day-old chicks.

The percentages of ‘degenerating’ germ cells, and the numbers of oögonial mitoses in irradiated ovaries vary between individuals, and do not appear to be dependent upon the dose of irradiation (Table 2). Ovaries exposed to 400 r. on the 11th day, however, contain large numbers of ‘degenerating’ germ cells as well as mitotically active oögonia (Table 2).

Since Experiments I and II involved identical procedures, bar the time of autopsy, a direct comparison between them is valid (Table 4). With a single exception (exposure at 19 days’ incubation), irradiated ovaries removed 2 days after hatching consistently contain more germ cells than do those, subjected to the same treatment, recovered 2 days after exposure. This finding indicates that oogenesis (i.e. the formation of new germ cells by the mitotic activity of surviving oögonia) occurs in all ovaries exposed at 9 to 17 days’ incubation between 2 days after exposure and the 2nd day after hatching. In contrast, the unirradiated left ovary at 17 and 19 days’ incubation contains more germ cells than does that of 2-day-old chicks, i.e. the population normally decreases with age (Table 4). In order to compare the relative change in the number of germ cells in irradiated and control ovaries, the figures shown in Table 4 have been expressed as percentages of the total number of germ cells normally present at 2 days after hatching (Table 5).

TABLE 4.

Comparison between numbers of germ cells at 2 days after hatching (Experiment I) and 2 days after irradiation (Experiment II)

Comparison between numbers of germ cells at 2 days after hatching (Experiment I) and 2 days after irradiation (Experiment II)
Comparison between numbers of germ cells at 2 days after hatching (Experiment I) and 2 days after irradiation (Experiment II)
TABLE 5.

Population of germ cells in irradiated ovaries, expressed as a percentage of the number present in unirradiated ovaries 2 days after hatching

Population of germ cells in irradiated ovaries, expressed as a percentage of the number present in unirradiated ovaries 2 days after hatching
Population of germ cells in irradiated ovaries, expressed as a percentage of the number present in unirradiated ovaries 2 days after hatching

The results show that the percentage increase in the number of germ cells is consistently lower after exposure to 400 than to 200 r. (Table 6). It would thus appear that irradiation depresses the regenerative capacity of surviving oögonia, the degree of depression being dose-dependent. As compared with unirradiated controls, irradiation on the 9th, 11th and 19th days reduces the percentage increase in the number of germ cells between 2 days after exposure and the 2nd day after hatching (Table 6). Ovaries removed 2 days after exposure to 200 r. on day 13, however, and to either 200 or 400 r. on days 15 and 17, show a greater percentage increase in the number of germ cells than that recorded for normal ovaries.

TABLE 6.

Percentage increase or decrease in the population of germ cells between 11 days’ incubation and 2 days after hatching

Percentage increase or decrease in the population of germ cells between 11 days’ incubation and 2 days after hatching
Percentage increase or decrease in the population of germ cells between 11 days’ incubation and 2 days after hatching

Qualitative changes

At 2 days after irradiation, histological changes in non-germinal elements are again minor. Cortical cysts were not observed.

Irradiation does not appear to retard the development of germ cells within the first 2 days after irradiation. Some ‘degenerating’ germ cells were greatly enlarged. It should be noted, however, that advanced stages of spontaneous atresia are also frequently associated with an increase in nuclear diameter (see Hughes, 1963).

The present results show that doses of 200 and 400 r. of X-rays are sufficient to cause marked radiolesions in the germ cells of female chick embryos, the response to radiation being dependent both on the dose of X-rays administered and on the age of the embryo at the time of exposure. The observation that the female germ cells are particularly radiosensitive at about the 11th day of incubation support the results reported by Moreng & Muller (1962).

During this period of high radiosensitivity, a large proportion of oögonia are dividing mitotically (Hughes, 1963). Between 11 and 19 days’ incubation, on the other hand, the percentage of germ cells dividing mitotically decreases, while that of cells entering the prophase of meiosis increases (Hughes, 1963). Since germ cells become progressively radioresistant during this period, it is evident that meiotic prophase is associated with a rise in radio-resistance. It appears that fewer germ cells survive 400 r. of X-rays administered on the 19th day of incubation, however, than is the case for specimens treated similarly on the 17th day. Since a proportion of oocytes enter the diplotene phase on day 19 (Hughes, 1963), it is possible—though by no means proven—that oocytes become more radiosensitive again as they pass from the pachytene to the diplotene phase.

The results of the present study are strikingly similar to those reported by Beaumont (1961,1962) for the foetal rat. Beaumont (1962) was able to correlate a rise in the radiosensitivity of female germ cells between the 8th and 15th days post coitum with their increasing mitotic activity. Oocytes in the rat, as in the chick, are relatively refractory as they pass through leptotene, zygotene and pachytene stages of meiotic prophase (Beaumont, 1961; Beaumont & Mandl, 1962). Moreover, the radiosensitivity of rat oocytes at early diplotene is less than that of oocytes at the ensuing, so-called ‘dictyate’ phase (Beaumont, 1962; cf. Beaumont & Mandl, 1962).

Observations on other mammals have been largely similar, though less clearcut (see Mandl, 1964). Using subsequent reproductive performance as their criterion, Rugh & Jackson (1958) showed that the germ cells of female mouse embryos become more radioresistant between 15-5 and 17-5 days post coitum:, this stage may correspond to the onset of meiosis (e.g. Brambell, 1927; Slizynski, 1961; Borum, 1961). Susceptibility to radiation damage is high between 11-5 and 16-5 days post coitum (see Russell, Badgett & Saylors, 1960). It should be noted, however, that Rugh & Jackson (1958) and Russell et al. (1960) used different strains of mice, and that the time of onset of meiotic prophase may vary considerably between strains (Slizynski, 1957,1961). In the absence of detailed descriptions of the ovary at the time of irradiation, it is impossible to say with certainty whether peak radiosensitivity in the mouse is correlated with a high incidence of oögonial mitoses. At the same time, there is evidence that the radiosensitivity of oocytes in the mouse increases progressively as they pass from the pachytene to the diplotene stage. Russell, Russell, Steele & Phipps (1959) observed that 300 r. of X-rays given to mice on the day of birth (when many oocytes are at pachytene) caused a slight depression in reproductive capacity, whereas 85 rad. given as continuous 137Cs-radiation during the 2nd week after birth induced early sterility. These observations have been confirmed by Cole, Habermeyer & Stolan (1960) and Peters & Levy (1963,1964). It is interesting to note that Essenberg & Zikmund’s (1938) report that chick ovaries become more radiosensitive between the 1 st and 2nd weeks after hatching also implies that the oocytes become more radiosensitive as they pass from early into late diplotene (cf. rat : Beaumont, 1961, 1962; mouse: Peters & Levy, 1963, 1964).

The observation that mitotically active oögonia are particularly susceptible to radiation damage conforms with the classic thesis of Bergonié & Tribondeau (1906) that undifferentiated tissues with a high mitotic index are extremely radiosensitive. The increase in sensitivity of germ cells in the chick between 9 and 11 days’ incubation is, however, associated with a slight fall in the mitotic index of germ cells (Hughes, 1963). Moreover, the phenomena of recovery and regeneration cannot account per se for the observed increase in radiosensitivity. If the numbers of germ cells present 2 days after exposure are expressed as percentages of the population in unirradiated ovaries, it becomes evident that a higher proportion is eliminated after exposure on the 11th than on the 9th day of incubation; yet the mitotic index in the unirradiated ovary is lower on the 11th than on the 9th day. A possible explanation is that oögonia, like spermatogonia type-B in the mouse (see Monesi, 1962), are particularly radiosensitive when approaching the last mitosis preceding meiosis. Indeed, it has been suggested that the last gonial division may differ in character from the preceding ones, being in some way intermediate between typical mitosis and meiosis (see Tobias, 1956; Rhoades, 1961). But cytological and cytochemical evidence that this applies to the last gonial division in female birds and mammals is, as yet, lacking.

The present experiments have revealed an interesting phenomenon relating to the regulation of the population of germ cells. Despite the fact that the number of germ cells in normal ovaries decreases between the 17th day of incubation and 2 days after hatching, the number in irradiated ovaries generally increases. There appears to be some ‘attempt’ to compensate for artificial depletion by irradiation —yet the treatment reduces the mitotic activity of oögonia, the inhibition being dose-dependent. These findings imply that, during the latter part of the incubation period, fewer germ cells degenerate in irradiated than in unirradiated ovaries, the proportion doing so being in some way related to the total available population of germ cells. Factors controlling the proliferation, differentiation and senescence of cells are not fully understood. It is possible that germ cells in the developing avian ovary compete with each other for some substance(s) essential for their continued existence. Another possibility is that germ cells themselves produce a substance which inhibits oogenesis and/or induces early senescence and death in some of their neighbours.

La radiosensibilité des ovogonies et des ovocytes chez /’embryon de poulet

  1. L’effet de l’irradiation aux rayons X des cellules germinales de l’ovaire de l’embryon de poulet au cours du développement dépend à la fois de la dose administrée et de l’Åge de l’embryon au moment de l’intervention. Les cellules germinales sont particulièrement radiosensibles à 11 jours d’incubation. Elles sont moins sensibles à partir de ce stade, jusqu’à 17 jours.

  2. Le pic de radiosensibilité de 11 jours coïncide avec une intense activité mitotique des ovogonies, mais non avec l’intensité maximale qui se place au 9e jour d’incubation. Les ovogonies qui subissent leur dernière mitose préméïotique ont probablement une radiosensibilité particulière. Les ovocytes paraissent devenir de plus en plus radiorésistants aux stades leptotène, zygotène et pachytène.

  3. L’irradiation X provoque un léger retardement dans le développement ultérieur de l’ovaire.

The expenses incurred in this study were defrayed from grants, made to Professor Sir Solly Zuckerman, F.R.S., by the Population Council, Inc. and the Medical Research Council.

The Author is indebted to the department of Scientific and Industrial Research for granting her a post-graduate Studentship, and to Dr Anita M. Mandl for her guidance, help and encouragement.

Beaumont
,
H. M.
(
1961
).
Radiosensitivity of oögonia and oocytes in the foetal rat
.
Int. J. Rad. Biol
.
3
,
59
72
.
Beaumont
,
H. M.
(
1962
).
The radiosensitivity of germ-cells at various stages of ovarian development
.
Int. J. Rad. Biol
.
4
,
581
90
.
Beaumont
,
H. M.
&
Mandl
,
A. M.
(
1962
).
A quantitative and cytological study of oögonia and oocytes in the foetal and neonatal rat
.
Proc. roy. Soc. B
,
155
,
557
79
.
Bergonié
,
J.
&
Tribondeau
,
L.
(
1906
).
Interprétation de quelques résultats de la radiothérapie et essai de fixation d’une technique rationelle
.
C. R. Acad. Sci., Paris
,
143
,
983
5
.
Borum
,
K.
(
1961
).
Oogenesis in the mouse. A study of the meiotic prophase
.
Exp. Cell Res
.
24
,
495
507
.
Brambell
,
F. W. R.
(
1927
).
The development and morphology of the gonads of the mouse. Part I. The morphogenesis of the indifferent gonad and of the ovary
.
Proc. roy. Soc. B
,
101
,
391
409
.
Cole
,
L. J.
,
Habermeyer
,
J. G.
&
Stolan
,
H. N.
(
1960
).
Effect of low-level X-irradiation dose fractionation on fertility in female mice
.
Int. J. Rad. Biol., Suppl
.,
361
7
.
Dantschakoff
,
V.
&
Lacassagne
,
A.
(
1932
).
Stérilisation par les rayons X de l’ébauche gonadique du poulet. Ses effets sur le développement de la gonade
.
C. R. Soc. Biol., Paris
,
109
,
1067
9
.
Essenberg
,
J. M.
&
Zikmund
,
A.
(
1938
).
An experimental study of the effects of roentgen rays on the gonads of the developing chick
.
Radiology
,
31
,
94
103
.
Franchi
,
L. L.
,
Mandl
,
A. M.
&
Zuckerman
,
S.
(
1962
).
The development of the ovary and the process of oogenesis
.
In The Ovary
(ed.
S.
Zuckerman
,
A. M.
Mandl
&
P.
Eckstein
), pp.
1
88
.
London
:
Academic Press, Inc
.
Gladstone
,
R. J.
&
Colwell
,
H. A.
(
1933
).
On some effects of X-rays on the developing chick embryo
.
J. Anat., Lond
.
68
,
85
95
.
Hughes
,
G. C.
(
1963
).
The population of germ cells in the developing female chick
.
J. Embryol. exp. Morph
.
11
,
513
36
.
Mandl
,
A. M.
(
1964
).
The radiosensitivity of germ cells
.
Biol. Rev
. (in the Press).
Monesi
,
V.
(
1962
).
Relation between X-ray sensitivity and stages of the cell cycle in sperma-togonia of the mouse
.
Radiation Res
.
17
,
809
38
.
Moreng
,
R. E.
&
Muller
,
H. D.
(
1962
).
Growth and fecundity of chickens irradiated during embryonic development
.
Radiation Res
.
16
,
574
.
Peters
,
H.
&
Levy
,
E.
(
1963
).
Effect of irradiation in infancy on the fertility of female mice
.
Radiation Res
.
18
,
421
8
.
Peters
,
H.
&
Levy
,
E.
(
1964
).
Effect of irradiation in infancy on the mouse ovary. A quantitative study of oocyte sensitivity
.
J. Reprod. Fértil
.,
7
,
37
45
.
Rhoades
,
M. M.
(
1961
).
Meiosis
.
In The Cell
(ed.
J.
Brachet
&
A. E.
Mirsky
), Vol.
111
, Chap. 1.
New York
:
Academic Press, Inc
.
Rugh
,
R.
&
Jackson
,
S.
(
1958
).
Effects of fetal X-irradiation upon the subsequent fertility of the offspring
.
J. exp. Zool
.
138
,
209
21
.
Russell
,
L. B.
,
Badgett
,
S. K.
&
Saylors
,
C. L.
(
1960
).
Comparison of the effects of acute, continuous and fractionated irradiation during embryonic development
.
Int. J. Rad. Biol
., Suppl.,
343
59
.
Russell
,
W. L.
,
Russell
,
L. B.
,
Steele
,
M. H.
&
Phipps
,
E. L.
(
1959
).
Extreme sensitivity of an immature stage of the mouse ovary to sterilization by irradiation
.
Science
,
129
,
1288
.
Slizynski
,
B. M.
(
1957
).
Meiotic prophase in female mice
.
Nature, Lond
.
179
,
638
.
Slizynski
,
B. M.
(
1961
).
The pachytene stage in mammalian oocytes
.
Nature, Lond
.
189
,
683
4
.
Tobias
,
P. V.
(
1956
).
Chromosomes, Sex-cells and Evolution in a Mammal
.
London
:
Percy Lund, Humphries & Co
.
Warren
,
S.
&
Dixon
,
F. J.
(
1949
).
Effects of continuous radiation on chick embryos and developing chicks. I. Growth rate, gonads and bone
.
Radiology
,
52
,
714
29
.