Screening on the effects of a daily 3h/6h exposure of female rats to chronic restraint stress on estrus cyclicity, estrogens and sexual behavior: role of Phyllanthus muellerianus

Abstract

Stress is an inevitable situation shown to impair reproductive health through inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Chronic stress in female rats is well known to disrupt estrus cyclicity, estrogen levels and sexual behavior. However, the extent to which restraint stress model disturbs estrus cyclicity remains inconsistent. Phyllanthus muellerianus is a plant used in traditional medicine to boost libido. This study investigated the impact of chronic stress on estrus cyclicity and related estrogen state, to evaluate the pro-sexual effects of Phyllanthus muellerianus. For this purpose, adult female rats were subjected to chronic restraint stress (CRS) for either 3h or 6h during 14, 21 or 28 days. Vaginal smear was checked daily to record the estrus stage. At the end of each CRS, elevated plus maze test, body weight growth, reproductive organ weights, plasma hormones and ovarian/uterine histology were examined. Further, aqueous and methanolic extracts of P. muellerianus at doses of 60 or 372 mg/kg were co-administered to female rats under 6h CRS during 21 days. Sexual proceptivity/receptivity, plasma hormones and reproductive organ weights were measured. Chronic stress during 21 days completely disrupted the estrus cyclicity by increasing irregular cycles. We observed an elevated corticosterone level and a drop in estradiol content. CRS led to oxidative stress in the ovaries coupled to a reduction of uterine epithelium height. P. muellerianus significantly prevented CRS-induced low sexual desire by increasing sexual proceptive and receptive behaviors while inhibiting aggressiveness. In addition, P. muellerianus improved plasma estradiol without any change in corticosterone levels. This study demonstrates that a daily 6h CRS during 21 days disturbs female reproductive system through complete blockage of estrus cyclicity and drop of estradiol content. Low sexual desire arising from hormonal imbalance can be reversed by P. muellerianus treatment.