LAUSR

AIMS Explore the effects of heat stress and psychological stress combined exposure on the uterus and its underlying mechanisms. MAIN METHODS Sixty female Sprague-Dawley rats were randomly assigned to four groups: control group, psychological stress group, high ambient temperature group, and high ambient temperature combined with psychological stress group. All treatments were administered for two weeks. During this period, the estrous cycle, body weights and rectal temperature were measured regularly. Then, ovarian weight coefficient, serum estradiol (E2) and progesterone (P) concentration, uterine histomorphological alterations, levels of tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD), and the expressions of ovarian hormone receptors, leukemia inhibitory factor (LIF) and its receptor, homeobox gene A10 (HoxA10), Wnt5a, Wnt7a, β-catenin, and P-β-cateninY142 in the uterus and endometrium were detected. KEY FINDINGS High temperature combined with psychological stress lead to body weight, body temperature, ovarian hormones and estrus cycle disorder, uterine gland ducts expansion and endometrial thickness reduction, and the decreased expression of endometrial receptivity markers (LIF and HoxA10). Further, disturbed expression of E2 and P receptors in endometrium, elevated MDA and TNF-α levels, and decreased Wnt5a, Wnt7a and P-β-cateninY142 content were found. Our data suggested that co-exposure to high temperature and psychological stress could aggravate uterine damage probably by inducing ovarian hormonal disorder and the subsequent oxidative stress and inflammation, and reduce the endometrial function through suppressing Wnt signaling. SIGNIFICANCE This will provide the scientific basis for improving female reproductive health, and preventing and treating reproductive disorders.