Gestational cadmium exposure-induced ovotoxicity delays puberty through oxidative stress and impaired steroid hormone levels

Abstract

Cadmium (Cd), an environmental pollutant, has been shown to be highly toxic to both humans and animals. Its widespread industrial use has led to its accumulation in the environment. Cd has been shown to target multiple organs following acute intoxication, causing nephrotoxicity, immunotoxicity, osteotoxicity, and reproductive toxicity. Cd can cross the placental barrier and cause a wide range of defects during fetal development. The current study was aimed to assess the effect of Cd on the female reproductive system. Female rats were exposed to Cd [50/200 ppm] from embryonic day 9 to 21 through drinking water. Serum steroid hormone concentrations, hematological parameters, antioxidant enzyme levels, and ovarian histopathology were described. Water consumption, gravid uterine/body weight decreased in both the doses of Cd-treated dams. The hematological parameters analyzed in rat pups showed a significant reduction in both doses of Cd studied, while hemoglobin showed a significant reduction in 200 ppm Cd treatment alone. MCHC levels did not show any variation in 50 ppm Cd treatment, while 200 ppm Cd treatment significantly increased. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and serum testosterone, estradiol, and progesterone were significantly decreased. The levels of hydrogen peroxide and lipid peroxidation were increased in 50 and 200 ppm Cd-treated rats. These changes were accompanied with disrupted ovarian histoarchitecture, an extended estrous cycle, and delayed pubertal onset in Cd-treated rats. The data generated from the present study suggest that gestational Cd treatment induces ovarian toxicity and reproductive dysfunction through increased oxidative stress.

Fig. 1

Effect of gestational exposure to Cd on histoarchitecture of control (a), 50 ppm Cd (b), and 200 ppm Cd (c) ovary in developing rats (PND10). PF primary follicle, ASF atretic secondary follicle, AO altered oocytes, DSF disorganized secondary follicle, Co cumulus oophorus, DO deformed oocytes, Oo oocytes, SF secondary follicle

Fig. 2

Effect of gestational exposure to Cd on histoarchitecture of control (a), 50 ppm Cd (b), and 200 ppm Cd (c) ovary in developing rats (PND21). Explanations and n values are same as given under Fig. 1

Fig. 3

Effect of gestational exposure to Cd on pubertal onset in developing rats. Each bar represents the mean and the vertical line above denotes the SEM of 12 female rats (from three mothers). See “Materials and Methods” for experimental details. Statistical significance of difference among groups at p < 0.05. Control versus experiment (a); 50 versus 200 ppm (b)

Fig. 4

Effect of gestational exposure to Cd on estrous cyclicity in developing rats. Explanations and n values are same as given under Fig. 3

Fig. 5

Effect of gestational exposure to Cd on the specific activities of ovarian SOD (a), catalase (b), GPx (c), GR (d), and GST (e). Each bar represents the mean and the vertical line above denotes the SEM of 24 female rats (from six mothers). See “Materials and Methods” for experimental details. Statistical significance of difference among groups at p < 0.05. Control versus experiment (a); 50 versus 200 ppm (b)

Fig. 6

Effect of gestational exposure to Cd on the specific activities of ovarian LPO (a), and H₂O₂ (b). Explanations and n values are same as given under Fig. 5