Pregabalin alters reproductive performance in male mice and causes congenital anomalies in offspring.

CONTEXT: Pregabalin is an anticonvulsant drug with analgesic activity for the treatment of neuropathic pain. AIMS: To valuate the toxicity of pregabalin in reproductive parameters, spermatogenesis, and teratogenicity in the offspring of mice. METHODS: Twenty male mice were randomly distributed into two groups: PGB group and group C (n =10 per group). The animals in the PGB group received, via gavage, 200mg/kg of pregabalin diluted in distilled water daily, for a period of 45days. Group C received distilled water under the same experimental design. KEY RESULTS: In the paternal parameters of the PGB group, there was a significant increase in the size of the testicles, morphological alterations in the spermatozoa, a decrease in the Johnsen score, an increase in the Leydig cells, and a decrease in the serum level of testosterone. In the intrauterine development parameters of females mated with males from the PGB group, a significant decrease in placental weight, weight and length of fetuses, and fetal viability rate was observed. There was a significant increase in the number of resorptions and post-implantation losses. The significant anomalies observed in the offspring were alteration in the size of the kidneys, absent metacarpals and phalanges, alteration in the sternum, and supernumerary thoracic vertebrae. CONCLUSION: Results suggest that pregabalin had toxic effects on the reproductive function of male mice and teratogenic potential. IMPLICATIONS: The findings of this study may provide new hypotheses, taking into account the risk-benefit ratio for male reproduction and offspring health.

Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model.

Conditions experienced in early life have long-lasting effects on offspring health. Despite this, little is known about how maternal exposure to drugs during pregnancy affects offspring teeth morphogenesis. In humans, omeprazole is a common drug used to mitigate Gastroesophageal Reflux Disease. Importantly, omeprazole is a non-specific proton-pump inhibitor, which may inhibit the proton pumps expressed in the developing tooth germ. To date, however, the effects of intrauterine life exposure to omeprazole on offspring tooth development remain unknown. In this study, we addressed this gap in a murine model. Pregnant female Swiss mice were exposed to daily doses of 40 mg/kg of omeprazole from the 5th to the 17th day of pregnancy and the effects of such exposure on offspring odontogenesis parameters such as morphological abnormalities, disruptions in the ameloblast and odontoblast layers and the presence of dentin matrix were measured. Omeprazole exposure significantly increased the prevalence (control: 21.6%; treatment: 60%; p = 0.001) and the risk (posterior mean and 95% credible interval; control: 0.230 [0.129; 0.347]; treatment: 0.593 [0.449; 0.730]) of offspring teeth morphological abnormalities, although there were no statistically significant effects of omeprazole exposure on other parameters of tooth development. These findings suggest that there are potential side-effects to offspring oral health of omeprazole use during pregnancy.

Congenital anomalies and spontaneous abortion in mice resulting from the use of escitalopram.

CONTEXT: Escitalopram (ESC) use during pregnancy has not been associated with teratogenic effects in fetuses. AIMS: To investigate whether ESC administered during pregnancy in mice induces maternal toxicity and teratogenicity in offspring. METHODS: Treated mice groups G1 and control G0 (n =15 per group). Administration of ESC (G1) and saline solution (G0) during pregnancy and euthanasia on the 18thday. Pregnant female mice were treated with ESC (20mg/kg, via gavage) or saline solution (control group) from the 5th to the 17thday of gestation, when implantation was consolidated. During intraembryonic development until the day before delivery, the drug had an influence on the development of alterations from its maintenance in the uterine environment and its development to the disturbance causing skeletal or visceral malformations. KEY RESULTS: The intrauterine development parameters that were altered by ESC treatment were: number of resorptions (G0: [0.93±0.24]); G1: [3.33±0.51]), post-implantation loss (G0: [3.95±1.34], G1: [13.75±3.62]) and reduced fetal viability: [97.30±1.00]; G1: [81.09±6.22]). Regarding fetal formation, the treated group had visceral malformations with a significant frequency: cleft palate (G0: [1.0%], G1: [11.86%]) and reduced kidneys (G0: [0%]; G1: [10.17%]). Regarding skeletal malformations, a higher frequency was observed in the following parameters: incomplete supraoccipital ossification (G0: [0%], G1: [15.25]), absence of ribs (G0: [0%], G1 (G0: [0%], G1 [15.25%]) and absence of one or more of the foot phalanges (G0: [1.0%]; 64%]). CONCLUSION: Results indicate that ESC is an embryotoxic and teratogenic drug. IMPLICATIONS: Until further studies are performed, greater caution is necessary in prescribing the drug to pregnant women.