Developmental immunotoxicity and its potential gender differences of perinatal exposure to 4-nonylphenol on offspring rats: JAK-STAT signaling pathway involved

The aim of our study was to explore the developmental immunotoxicity (DIT) and its potential gender differences of perinatal exposure to 4-nonylphenol (4-NP), which was significant for the risk assessment of 4-NP exposure to fetuses and infants. Wistar pregnant rats were given the National Institution of Health (NIH)-31 modified feed containing 0, 10, 100 and 500 mg/kg 4-NP from the gestation day (GD) 6 to the postnatal day (PND) 21. At PND21, the offspring rats were randomly selected to detect developmental immunotoxicity related indicators. Results suggested that high-dose 4-NP perinatal exposure caused growth retardation in infancy of male offspring rats, which was not obvious in female offspring rats. Also, 4-NP perinatal exposure induced DIT (mainly manifested as immunosuppression) with potential gender differences, including decreased weight of immune organs, suppressed immune function, decreased ratio of transforming growth factor (TGF)-beta/interleukin (IL)-17A, increased ratio of T helper (Th) 17/regulatory T (Treg) cells et al. In addition, exploration of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway showed that JAK-STAT pathway mediated the leftward of Th17/Treg cells balance. Furthermore, the DIT to female offspring rats was more sensitive than to the males, which may be related to the differences of biological processes involved and needed to be further explored.