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The female guinea-pig has been shown to represent a good model to investigate the genetic hazard of ionizing radiation in humans. The sensitivity of the guinea-pig oocytes to radiation-induced chromosome aberrations was, therefore, studied at different stages of oocyte and follicular growth. The sensitivity of oocytes enclosed in small follicles (15 weeks before ovulation) was found to be low and comparable to that of immature oocytes present at birth. The sensitivity of growing oocytes remained low and almost constant until 3 weeks before ovulation, from which time it began to increase. The most dramatic increase of sensitivity occurred during the last week preceding ovulation: about 90% of oocytes X-irradiated with 4Gy, 2 days before ovulation showed one or more chromatid interchanges, as compared to 20% for those irradiated with the same dose 1 week earlier. A comparison of our results with those found by others in the mouse shows that considerable differences of sensitivity exist between oocytes of these two species irradiated at similar stages of development. The possible reasons for these differences are discussed.

In a previous study, we showed that the guinea pig constitutes one of the best models to evaluate the genetic risk associated with an irradiation of the human female germ cells. Herewith, experiments were undertaken to evaluate the chromosomal radiosensitivity of oocytes of this species at two different stages of follicular development, separated by only 1 week. Female guinea pigs were X-irradiated on the ovaries, at either the beginning (day 3) or the middle (day 10) of the 17-day oestrous cycle. The doses delivered were 1 or 2 Gy. Meiotically competent oocytes were collected 1 week after irradiation (day 3) or immediately thereafter (day 10), and they were cultured to the metaphase of the first meiosis (MI) and examined for the presence of chromosome aberrations. Our data demonstrated a dramatic increase in the radiosensitivity of the oocyte during this short time interval: oocytes irradiated at the beginning of the oestrous cycle had a low frequency of chromosome aberrations, while those irradiated at the middle of the oestrous cycle (when growing Graafian follicles are clearly visible at the surface of the ovaries) exhibited heavy chromosome damage. However, we also found that oocytes irradiated at the middle of the oestrous cycle were eliminated from the ovaries in a few days, after their evolution to the MII stage. The stimulation of the first meiotic division by radiation required less than 24 h after doses of 1 or 2 Gy and was probably due to a rapid atresia of the large follicles containing the oocytes. On the basis of these results, it can be concluded that the radiosensitivity of the nearly mature guinea pig oocyte (1 week before ovulation) is clearly much higher than that of the corresponding stage in the mouse, both in terms of sensitivity to killing and to induction of chromosome aberrations.

In female mammals, the immature oocyte is the germ cell most at risk, from the genetic point of view. We have previously shown that ovaries of newborn guinea pigs contain a great majority of immature oocytes and small numbers of maturing oocytes. At this time, all immature oocytes are in a typical diplotene stage, comparable to that of the human resting oocyte. Furthermore, the LD50 of the guinea pig oocytes is about 4 Gy, like that of human oocytes. Consequently, performing genetic studies on guinea pig oocytes irradiated just after birth constitutes a very useful approach to predict the mutational response of the human resting oocyte. Female guinea pigs were X-irradiated with 1 or 2 Gy within 24 h of birth, and their meiotically competent oocytes were collected and cultured to the metaphase I stage, 1 year after treatment, ensuring that all oocytes were at the immature stage at the time of irradiation. The proportion of oocytes that showed chromosome aberrations (breaks, fragments or interchanges) was only 1-2% Gy(-1). Although not definitive, these results provide support for a low risk in women from an exposure of the immature oocyte to low doses of radiation.

Female mice of the BALB/c and CF1 strains were mated and irradiated with various doses of X-rays 7 h after presumed fertilization. 18 days later, females were killed and their uteri examined for prenatal mortality at the different stages of development. Living fetuses were weighed and examined for the presence of external malformations. A number of them were also examined for skeletal anomalies. Radiation induced mainly a dose-dependent increase of the preimplantation loss in the BALB/c strain and of the early postimplantation loss in the CF1 strain. Embryos of the BALB/c strain were refractory to the induction of teratogenic effects after such preimplantation irradiation. In CF1 mice, the frequency of malformed fetuses increased regularly after irradiation, the difference with controls being significant for the doses of 10, 50 and 100 cGy. Dwarfism occurrence also appeared to be increased by irradiation in this strain, although the importance of this effect varied depending on the criterion chosen for the assessment of dwarfs. With the definition proposed in the present paper, the increase in the frequency of dwarfs paralleled that of malformed fetuses, being significant after doses of 50 and 100 cGy. Irradiation did not increase the frequency of skeletal anomalies. A careful examination of the various data obtained to data led us to conclude that radiation may possibly be teratogenic in several mouse strains, when administered as early as during the one-cell stage and, to a lesser extent, during the following preimplantation stages. However, early prenatal mortality will remain by far the greatest risk associated with an exposure to radiation during this period. Moreover, the relativity of the risk of abnormality due to such irradiation should be considered in the context of the high prevalence of developmental defects spontaneously occurring during human pregnancy.