Prepubertal and Adult Ovarian Response to di(2-ethylhexyl) phthalate: Apoptosis, Proliferation and Nrf2 Activation
Melike Sapmaz-Metin (TR)
[Sapmaz-Metin] Trakya University
Objectives: Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer in a variety of consuming products. There are limited reports concerning the female reproductive toxicity of DEHP as well as revealed inconsistent findings. Therefore, the aim of the study was evaluate the high oral dose DEHP toxicity in the prepubertal and adult rat ovary tissue. Materials&Methods: Prepubertal and adult animals divided into two sets. Each set consisted 12 animals; first set from prepubertal, 21 days old female Wistar albino rats and the second set from sexually mature, 3 months old virgin female rats. Each set has a group received 1000mg/kg DEHP by gavage (10 consecutive days), and it’s corresponding control group. At the end of the experiment ovaries were harvested and paraffin inclusion was proccesed. Atresia was detected by TUNEL method in the ovarian sections. Proliferation (proliferating cell nuclear antigen (PCNA)) and cellular antioxidative response (nuclear factor erythroid 2–related factor 2 (Nrf2)) were determined by immunohistostaining. Results: Prepubertal exposure to DEHP increased cell proliferation in the ovary without affecting follicular atresia. In the adult animals, DEHP induced slight decrease in the PCNA labeling, however, atresia increased markedly. Nrf2 immunoreactivity was observed in the granulosa cells, oocytes and interstitial gland cells in each of the control and DEHP groups. Both of the prepubertal and adult exposure to DEHP decreased Nrf2 immunoreactivity compared to respective controls. Conclusion: In conclusion, DEHP as a xenoestrogen induced maturation as well as follicular atresia in the prepubertal animals. In the adult female rats DEHP played a role as a oxidative stres inducer and increased atreasia whereas decreased PCNA and Nrf2 immunoreactivity in the rat ovary.