For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.

The two different culture media employed in this study had a significant (p<0.01) impact both on the dynamics of post-fertilization development and embryo quality, as assessed by subjective morphological parameters. Media-A had a significantly higher proportion of embryos reaching the blastocyst stage at <110 hours and a higher proportion of top-quality blastocysts. The area under the receiver operating curve obtained from the ML models was 80.9% for Media-A and 80.5% for Media-B. The models were deployed as a web-based service running a Python script to extract the relevant morphokinetic and clinical parameters of embryos in real-time to provide the predicted probability of 110-hour blast formation.CONCLUSIONS: There were significant differences in the rate of embryo development and the proportion of top-graded blastocysts between the two culture media. The models developed to estimate the probability of reaching the blastocyst stage in <110 hours had a similar ROC-AUC but different structures to account for the different dynamics of development induced by the culture media.IMPACT STATEMENT: This work showcases the importance of continuously evaluating the characteristics of embryo development as the IVF laboratory evolves. Models implemented for embryo evaluation need to be adjusted accordingly. This study also suggests that embryo development is significantly impacted by laboratory-specific parameters; therefore, ML models should be tailored to the ART setting in which they will be utilized. Finally, deploying these models in platforms that allow for rapid and seamless updates to new versions increases the ability of these decision-support systems to adapt to the continuously evolving IVF laboratory.SUPPORT: Institutional