Huperzine-A administration recovers rat ovary function after sympathetic stress

Chronic cold stress affects ovarian morphology and impairs fertility in rats. It causes an ovarian polycystic ovary (PCOS)-like phenotype, which resembles PCOS in women. The mechanism of cold stress action involves increased ovarian noradrenaline (NA) levels, which remain elevated after cessation of cold stress. By contrast, ovarian acetylcholine (ACh) levels are only transiently elevated and returned to control levels after a 28-day post stress period. Because ACh can exert trophic actions in the ovary, we hypothesised that a sustained elevation of ovarian ACh levels by intraovarian exposure to the ACh-esterase blocker huperzine-A (Hup-A) may interfere with cold stress-induced ovarian changes. This possibility was examined in female Sprague-Dawley rats exposed to cold stress (4°C for 3 h day^-1 for 28 days), followed by a 28-day period without stress. To elevate ACh, in a second group Hup-A was delivered into the ovary of cold stress-exposed rats. A third group was not exposed to cold stress. As expected, cold stress elevated ovarian NA, reduced the number of corpora lutea and increased the number of follicular cysts. It increased plasma testosterone and oestradiol but decreased plasma levels of progesterone. In the Hup-A group, ovarian levels of both, NA and ACh, were elevated, there were fewer cysts and normal testosterone and oestradiol plasma levels were found. However, progesterone levels remained low. Most likely, low progesterone was associated with impaired mating behaviour and low pregnancy rate. We propose that elevated intraovarian levels of ACh are involved in the rescue of ovarian function, opening a target to control ovarian diseases affecting follicular development.