Study of the Effect of Acetaminophen on Reproduction Using the Female Mouse Model

Abstract

Acetaminophen is not considered a typical non-steroidal anti-inflammatory drug (NSAID) and its effects on reproduction have not been studied extensively as other NSAIDs. Acetaminophen is known to act through the inhibition of prostaglandin synthesis and activation of the endocannabinoid system, thus can be associated with the regulation of mammalian reproductive processes through the same systems. To provide further evidence, this study was devised to establish the effect of acetaminophen on female reproduction. Specifically, its impact on the oestrous cycle, reproductive hormone production, ovulation, and implantation. Female Swiss white mice aged between six and eight weeks were used for the study. The mice were sourced from Kenya Medical Research Institute (KEMRI) and International Livestock Research Institute (ILRI). The mice were randomly divided into control and treatment groups of five (5) mice each. Throughout the experiments, mice in the treatment group received 200mg/kg of acetaminophen, while the control group received 0.5ml of normal saline via oral gavage. There was no significant difference in the number and length of oestrous cycles was observed in the treatment (3.54±0.155 and 5.52±0.187) and control (3.54±0.144, and 5.38±0.172) groups from the study. There was however, a significant reduction in the frequency of proestrus in the treatment group (P≤0.05). There was no significant difference in FSH, LH, and estrogen levels. However, there was a delay in the production of the FSH, LH, and estrogen, with peak production seen during metestrus. There was a significant reduction in progesterone levels in the treatment group (P≤0.05). A significant reduction in the number of implantation sites in mice treated with acetaminophen in pre (P ≤ 0.05) and post-coitus (P ≤ 0.01) treatment regimes was also seen. Upon withdrawal of acetaminophen, implantation sites of mice in the treatment group did not differ from those in the control group. On histology there was an increase in the number of secondary follicles in the treatment group compared to the control. Both secondary and tertiary follicles had degenerative changes in the treatment group. There was also a disruption on the endometrial lumen and a reduction in the number of villi in the treatmetn group when compared to the control. From the study, acetaminophen demonstrated some negative effects on reproduction in the mice and, therefore, has potential for use to lower fertility. However, further studies are required to fully study how it affects reproduction in females.