Background: Bisphenol A (BPA) is one of the most commonly produced chemicals in the world. BPA is used in products such as food packaging, personal care products, detergents, and plastic bottles. This study was conducted to determine the effect of BPA on fetal bone development. Material and methods: In this study, 16 pregnant female Sprague-Dawley rats were used. The rats were divided into four groups: the control group and 0.5 mg/kg/day, 5 mg/kg/day, and 50 mg/kg/day dose BPA groups. The skeletal system development of fetuses was examined with double skeletal and immunohistochemistry (IHC) staining (tartrate resistant acid phosphatase (TRAP) and the alkaline phosphatase (AP) expressions) methods. Results: The highest ossification rates in the humerus, radius, and ulna were detected as 41.05%, 39.25%, and 37.26% in the control group, respectively. The highest ossification rates in the femur, tibia, and fibula were detected as 23.04%, 30.73%, and 32.78% in the control group, respectively. Statistically significant differences were found between control and experimental groups in the TRAP and AP expression of the femur by IHC staining (p < 0.001). Conclusion: Exposure to BPA during pregnancy adversely affected ossification and bone growth. A dosedependent decrease was observed in the rate of ossification.

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated. Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples. TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method. The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P<0,001). No significant difference in samples of the LDC group (P>0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.

Objective This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. Methods In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150–200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low‐dose CBZ (10 mg/kg/day) group, medium‐dose CBZ (25 mg/kg/day) group, and high‐dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate‐resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. Results According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. Significance It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

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