Cold Stress Induced PCOS Like Phenotype in Rats Partially Reversed by Huperzine‐A

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Cold stress induced PCOS like phenotype in rats partially reversed by Huperzine‐A

Huperzine‐A administration recovers rat ovary function after sympathetic stress

An experimental study was conducted using Sprague-Dawley rats to test if the PCOS like phenotype caused by cold stress could be blocked by administration of huperzine‐A.

A total of 60 rats were used and evenly divided into 3 groups; (1) Control, (2) Stress, (3) Stress + Huperzine‐A. Cold stress was induced in the stress groups for 3 hours/day, 5 days a week at 4°C for a total of 4 weeks. Acetylcholine (ACh) levels were measured along with hormones (testosterone, oestradiol, progesterone, LH). Each female rats oestrous cycle was recorded and morphometric analysis of their ovaries performed to evaluate follicle growth. The female rats were then mated with males to evaluate the effect on fertility.

Initial analysis confirmed that ACh levels in the ovaries of both stress groups (Stress, Stress + Huperzine‐A) increased as shown previously. In the later group, ACh increased further post stress period confirming that huperzine‐A blocked ACH enzyme activity.

Quantitative analysis of the morphological changes showed a statistically significant decrease in the proportion of secondary and healthy antral follicles in the stress group, resulting in a significant increase in the number of atretic antral follicles and cysts followed by a decrease in corpora lutea. Interestingly huperzine‐A administration in the Stress + Huperzine‐A reversed this effect and caused an increase in the number of corpora lutea greater than 700µm in size.

Hormone analysis showed a significant decrease in progesterone, testosterone and estradiol for the stress only group. Similarly huperzine‐A administration in the Stress + Huperzine‐A group reversed the effect on testosterone and estradiol, however progesterone levels remained significantly lower. In the stress only group oestrous cycles were significantly interrupted and therefore lower. Huperzine‐A administration reversed this effect to the extent that no significant difference was found between the Control and Stress + Huperzine‐A group. Interestingly LH levels did not differ significantly across the 3 groups.

Finally female mating behaviour was impaired in both stress groups however the average number of live pups born per rat in all 3 groups was not significantly different.


  1. Human and rat reproductive biology is close although not identical
  2. Further studies required to confirm if cold stress causes similar effects in women

Similar studies

Riquelme R, et al. (2019). Role of ovarian sympathetic nerves and cholinergic local system during cold stress.

Du Y, et al. (2018). Acetylcholine and necroptosis are players in follicular development in primates.

Squicciarini V, et al. (2018). Role of RFRP-3 in the development of cold stress-induced polycystic ovary phenotype in rats.

Bernuci M P, et al. (2013). Transitory activation of the central and ovarian norepinephrine systems during cold stress-induced polycystic ovary in rats.


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