Over the past decades, the incidence of non-communicable chronic diseases (NCDs), such as cardiovascular diseases, respiratory tract diseases, and diabetes has alarmed scientists worldwide. As such, the 2030 Agenda for Sustainable Development from World Health Organization (WHO) recognizes NCDs as a major challenge to sustainable development (WHO, 2023). Epidemiological and experimental studies have demonstrated that early life exposures to environmental adverse conditions have a significant influence on the increased incidence of chronic diseases throughout the life course (Heindel et al., 2015). In this regard, the Developmental Origins of Health and Disease (DOHaD) concept has been consolidated as a conceptual framework that asserts the causal effects between early life exposure and the emergence of chronic diseases. The DOHaD states that exposure to inappropriate conditions during periods of high vulnerability, such as intrauterine and early postnatal life (Barker, 1990; Suzuki, 2018), can lead to developmental imprinting and epigenetic reprogramming, making individuals more susceptible to developing chronic diseases, such as cardiovascular diseases (Espírito-Santo et al., 2022), type 2 diabetes (Carlos et al., 2022)andobesity (Sun et al., 2023) with aging.

Although maternal malnutrition has been identified as an important risk factor for the development of metabolic and cardiovascular diseases (Daniel et al., 2016; Langley-Evans and Sculley, 2006; Vithayathil et al., 2018), experimental evidences has demonstrated the negative impact of maternal exposure to a low protein diet (LPD) on the offspring male reproductive health (Colombelli et al., 2017), such as delay in onset of puberty, testicular weight, and decreased fertility rates (Rodríguez-González et al., 2012; Zambrano et al., 2014). Recent studies showed that maternal exposure to LPD affects prostate developmental biology through the deregulation of sex hormones, leading to impairment of prostate growth in young rats and increasing the incidence of prostate carcinogenesis with aging (Colombelli et al., 2017; L. M. Portela et al., 2021; Santos et al., 2019). The influence of environmental exposure on rodent prostate developmental biology occurs mainly during the first 15 days of life when the androgens synthesized by the fetal testis induce the formation and growth of the epithelial buds (Prins and Putz, 2008).

In spite of the essential role of androgens in the development and function of the prostate (Prins, 2008; Prins et al., 2006), it has been demonstrated that estrogens also play an important role during normal prostate development, and exposure to high levels of estrogens early in life can epigenetically reprogram prostate biology, predisposing to carcinogenesis with aging (Cheong et al., 2016; Gardner, 1995; Nelles et al., 2011). Prins and collaborators demonstrated that male rats exposed to high levels of estrogen at post-natal day are at high risk to develop Prostate Cancer (PCa) with aging (Prins et al., 2001; Prins and Ho, 2010). It is known has been little information about how maternal malnutrition affects the prostate gene expression profile in young offspring, with potentially long-lasting effects on prostate health with aging. Our data demonstrated that maternal exposure to LPD deregulated molecular pathways involved with normal prostate development, leading to impairment of prostatic growth in young offspring. We further showed that changes in gene expression profile persist throughout the life course, predisposing rats to develop PCa with aging. Interestingly, we identified molecular markers commonly deregulated among young and old rats with those observed in patients with PCa. Overall, these data highlight the potential role of maternal malnutrition as a key environmental factor involved with the developmental origins of PCa in offspring rats.