Radiosensitivity of Oogonia and Oocytes in the Foetal Rat

Beaumont, Heather M.

doi:10.1080/09553006114550071

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…If depletion of PGCs was not compensated through extra proliferation of oogonia, this must result in fewer oocytes in the ovary. Studies investigating the exposure of female rat fetuses to low doses of radiation [31] or busulfan [32] have shown that the ovary is sensitive to these agents between E13.5 and 17.5. Hence, it is likely that the ovary will be sensitive to CP throughout the latter half of fetal development.…”

Section: Discussionmentioning

confidence: 99%

Fetal Cyclophosphamide Exposure Induces Testicular Cancer and Reduced Spermatogenesis and Ovarian Follicle Numbers in Mice

et al. 2014

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Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼70% of control and induced atrophic seminiferous tubules in ∼30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

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Section: Discussionmentioning

confidence: 99%

Fetal Cyclophosphamide Exposure Induces Testicular Cancer and Reduced Spermatogenesis and Ovarian Follicle Numbers in Mice

et al. 2014

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“…Of the limited number of studies designed to test the ability of the prenatal mammalian female germ cell to survive an exposure to ionizing radiation, the works of Beaumont (1961Beaumont ( , 1962 are probably the most thorough. She inter¬ preted the response of the prenatal rat through counts of oocytes surviving to 25 days post partum and found that 100 R of X-rays inflicted negligible damage to the germ-cell population prior to Day 15 of gestation, but radiation administered at Day 15 reduced oocyte numbers to 15% of control values.…”

Section: Radio-response Of the Prenatal Bovine Ovarymentioning

confidence: 99%

Development and Radio-Response of the Prenatal Bovine Ovary

Erickson¹

1966

Reproduction

163

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Qualitative observations of forty-nine bovine foetuses taken at varying stages of gestation revealed the following: (1) the germinal ridge is established at the 32nd day of gestation; (2) due to the formation of the tunica albuginea of the primitive testis, foetal sex is distinguishable by Day 39; (3) meiosis begins in ovaries at 75 to 80 days post coitum; (4) oogonial mitosis is discontinued by 150 to 170 days; (5) the majority of the oocytes have attained their stage of rest (pachytene) and are enveloped in primordial follicles by Day 170; and (6) vesicular follicles appear in ovaries at Day 250 of gestation.Total germ-cell numbers, based on volumetric determinations or direct counts, increased from a low of approximately 16,000 at Day 50 to a high of 2,700,000 at Day 110. From Day 110 numbers declined abruptly to 107,000 at Day 170 and the ovaries of four foetuses at 270 days of gestation (average length of gestation, 283 days) contained an average of 68,000 \m=+-\ 21,000 germ cells.Seventy prenatally irradiated (400 R, whole-body to dam) and twenty-five non-irradiated heifers were slaughtered at either 9 or 23 months of age. Microscopic examinations of their ovaries revealed that irradiation was apparently without effect during the interval of 17 to 59 days of gestation, and of questionable effect during the interval of 59 to 119 days of gestation. Irradiation administered during the 119-to 154-day interval, however, diminished germ-cell numbers by an average of 68%. From Day 154 to term, irradiation was again without effect. The mitotically active oogonium was probably the cell affected during the interval of 59 to 119 days of gestation and the drastic germinal decline during the 119-to 154-day interval was believed to be related to the progression of oocytes from zygotene to pachytene, a transition during which the oocyte under normal conditions is highly susceptible to death.

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“…Beaumont [2,3] investigated sensitivity of germ cells to X-irradiation at various stages of ovarian development in rats and found that the radiosensitivity was the highest on the 15th day of intra-uterine life, and then shortly after birth.…”

Section: Discussionmentioning

confidence: 99%

Effect of lifetime intake of organically bound tritium and tritiated water on the oocytes of rats

Pietrzak-Flis

Wasilewska-Gomułka

1984

Radiat Environ Biophys

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Rats were continuously exposed to constant activity of tritium in drinking water (HTO group) or to tritium organically bound in food (T-food group) in the period from conception of F1 generation through maturity. Female offspring were killed at the age of 21 and 71 days and the oocytes in their ovaries were counted. Mean dose rates absorbed in the ovaries were for the HTO groups 7.25 +/- 0.37 and 14.73 +/- 0.79 mGy/day and for the T-food group 4.84 +/- 0.25 mGy/day. Reduction in the oocyte number in the ovaries of females exposed to tritiated food was bigger than in the ovaries of females exposed to tritiated water. The dependence of the survival of small oocytes on the dose rate and the corresponding total accumulated dose had an exponential character. The damaging effect of tritium was for the period from conception to 21 days of age bigger than from 21 to 71 days of age. Of all stages of oocyte development, the highest sensitivity to tritium irradiation was observed in small oocytes and oocytes with one complete layer of follicle cells. As a result, relative number of growing and large oocytes increased.

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Radiosensitivity of Oogonia and Oocytes in the Foetal Rat

Cited by 18 publications

References 15 publications

Fetal Cyclophosphamide Exposure Induces Testicular Cancer and Reduced Spermatogenesis and Ovarian Follicle Numbers in Mice

Fetal Cyclophosphamide Exposure Induces Testicular Cancer and Reduced Spermatogenesis and Ovarian Follicle Numbers in Mice

Development and Radio-Response of the Prenatal Bovine Ovary

Effect of lifetime intake of organically bound tritium and tritiated water on the oocytes of rats

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