Development and vulnerability of rat brain and testes reflected by parameters for apoptosis and ornithine decarboxylase activity

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) I 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.