The uterus is a highly adaptable organ that undergoes substantial morphological and functional transformations throughout a female’s reproductive life. These changes are particularly pronounced during ovulation, mating, and early embryonic development. During ovulation and mating, the uterus facilitates sperm migration through coordinated myometrial contractions (Hawk, 1983) while simultaneously activating neutrophil-mediated clearance of potential pathogens (Katila, 2012, Schuberth et al., 2008). The uterine antimicrobial defenses reach their peak around ovulation (Wira et al., 2014).

After fertilization in the oviduct, the embryo requires approximately 2.5–3 days to migrate to the uterus in mice, a process that is critically dependent on the uterine environment (Hoffmann et al., 1993). Embryo survival and development rely heavily on uterine conditions that support cellular growth, differentiation, and placentation. However, an unfavorable uterine environment, such as one affected by inflammatory conditions (Ribeiro et al., 2016), can result in embryonic mortality.

Early embryo loss is a common pregnancy complication that primarily occurs before implantation and profoundly influences reproductive outcomes in both humans and other mammals. The preimplantation period represents a particularly sensitive window for embryo survival. Studies indicate that implantation failure is the major cause of early embryonic loss (Koot et al., 2012). Although the exact number of embryos lost before natural implantation is difficult to determine, preimplantation loss in healthy women is estimated to range from 10 % to 40 %, and the total embryonic loss from fertilization to delivery is approximately 40–60 % (Jarvis, 2020). Similarly, gestational embryo loss rates reach 30–50 % in sows (Wang et al., 2019), and 47.9 % of pregnancy losses in beef cattle occur during the early embryonic stage (Reese et al., 2020). Collectively, these findings underscore that early embryonic loss is a major determinant of pregnancy success across mammalian species.

The uterine environment, which facilitates sperm transport, bacterial clearance, and early embryonic development, is primarily shaped by secretions from endometrial cells and molecules derived from the bloodstream. The transfer of these molecules from the blood into the uterine lumen involves active and selective processes, including the transport of specific substances such as amino acids and ions (Malayer et al., 1988). Within 7–8 days after estrus in cattle, substantial alterations occur in both endometrial gene expression profiles and protein secretion patterns (França et al., 2017, McRae, 1988, Mitko et al., 2008, Tribulo et al., 2018). During this period, changes in the composition of small molecules within the uterine fluid have also been reported, particularly in amino acids (França et al., 2017, Hugentobler et al., 2007), as well as ions and sugars (Hugentobler et al., 2010, Schultz et al., 1971). Simultaneously, several metabolites present in uterine fluid have been shown to influence preimplantation embryo development and mediate maternal–embryo communication (Tríbulo et al., 2019).

Therefore, the present study aimed to characterize the dynamic metabolic changes occurring in the uterus within four days after mating in a mouse model, thereby enabling precise tracking of early implantation-related events. We hypothesized that alterations in the uterine metabolome during this period are critical for uterine immune adaptation and for promoting early embryonic development. In addition, investigating the preimplantation uterine environment in mice provides a convenient model for understanding the physiological processes of the female reproductive system and offers valuable insights for preventing embryo loss in assisted reproduction and addressing recurrent implantation failure and early pregnancy loss.