Effects of EP-1 exposure during lactation on the emotion, social behavior, gonadal metabolomics, and related receptors in the brains of adult offspring in Kunming mice.

Infertility control with EP-1 (quinestrol: levonorgestrel = 1:2) has proven effective in a variety of rodents. Previous studies have focused on the effects of EP-1 in terms of sterility; however, little is known about its cross-generational impact. In this study, the emotional and social behavior, gonadal metabolomics, serum hormone levels, and related brain receptors in adult offspring were examined following exposure to EP-1 (3 or 5 mg/kg), which was administered to dams 3 and 10 days postnatally by gavage. The results showed that EP-1 exposure enhanced anxiety-like behavior in males and diminished social behavior in both females and males. EP-1 exposure reduced the levels of l-glutamine and l-glutamic acid in the ovaries and those of l-glutamine, L‑serine, and l-phenylalanine in the testes, possibly resulting in metabolic abnormality and decreased estradiol and testosterone levels in serum. Furthermore, EP-1 exposure increased the expression of dopamine 1 receptor (D1R) in the nucleus accumbens (NAc), estrogen receptor α (ERα) and oxytocin receptor (OTR) in the medial preoptic area (MPOA), and that of ERα in the ventrolateral region of ventromedial hypothalami of females; contrastingly, it decreased the expression of vesicular GABA transporter in the medial amygdala while increasing that of D1R in the NAc and that of ERα and OTR in the MPOA of individual males. In conclusion, EP-1 exposure during lactation enhanced anxiety-like behavior in males, reduced sociality, affected gonadal function, reduced sex hormone levels, and altered the relative expression of receptors in the brain regions that regulate social behaviors in all offspring mice.