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Development and vulnerability of rat brain and testes reflected by parameters for apoptosis and ornithine
Henrik Rye Lam1, Majken Dalgaard, Ole Ladefoged
1Institute of Food Safety and Toxicology, Danish Veterinary and Food Administration, Soeborg.
Background And Purpose:
Awareness of effects of chemicals on brain and sex organs during organogenesis is increasing. Balance between apoptosis and ornithine decarboxylase (ODC) activity has an essential role for final structure and function of these organs. It is important to localize stages in development where these processes may be particularly vulnerable to chemicals. We describe reference data on apoptosis and ODC activity in brain and testes.
Methods:
Brain and testes specimens were obtained during gestational days (G) 15 to 21 and on postnatal days (P) 1 to 60, and ODC activity and parameters of apoptosis (DNA laddering and Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling-staining) were investigated.
Results:
Brain ODC activity reaches maximum at G19 and thereafter rapidly decreases until P7. Apoptotic DNA laddering occurs in the brain from G17 to P7. Significant apoptotic ladders were not detected between P9 and 60. In the testes, apoptotic laddering was weak from G21 to P15, but increased significantly from P15 to 60. Histologic examination and DNA laddering analyses revealed low-level germ cell apoptosis from G15 to P11. At onset of spermatogenesis at P15, the number of apoptotic germ cells increased markedly.
Conclusions:
Brain ODC activity and apoptosis from G15 to P7 and at the onset of testes apoptosis at P15 are relevant markers for chemically induced developmental toxicity in these organs.
Insights
Chemicals can harm developing brains and testes. This study tracked apoptosis and ornithine decarboxylase (ODC) activity, finding key vulnerable periods in development for these organs.
Area of Science:
- Developmental toxicology
- Neuroscience
- Reproductive biology
Background:
- Chemical exposure during organogenesis poses risks to brain and sex organ development.
- Apoptosis and ornithine decarboxylase (ODC) activity are crucial for normal organ structure and function.
- Identifying developmental windows of vulnerability to chemical insult is critical.
Purpose of the Study:
- To establish reference data for apoptosis and ODC activity in the developing brain and testes.
- To pinpoint critical developmental stages where these organs are most susceptible to chemical disruption.
- To inform developmental toxicity assessments.
Main Methods:
- Brain and testes specimens collected from gestational day 15 to postnatal day 60.
- Assessed ornithine decarboxylase (ODC) activity.
- Investigated apoptosis using DNA laddering and TUNL staining.
Main Results:
- Brain ODC activity peaked at gestational day 19, declining by postnatal day 7.
- Apoptotic DNA laddering in the brain occurred from gestational day 17 to postnatal day 7.
- Testicular apoptosis, particularly in germ cells, increased significantly from postnatal day 15 onwards, coinciding with spermatogenesis onset.
Conclusions:
- Brain ODC activity and apoptosis between gestational day 15 and postnatal day 7 are key indicators of developmental toxicity.
- The onset of testicular apoptosis at postnatal day 15 serves as a relevant marker for chemical-induced toxicity.
- These findings provide crucial reference points for assessing developmental risks of chemical exposures.