Locus Coeruleus Mediates Cold Stress-Induced Polycystic Ovary in Rats

Abstract

Previous reports about the rat ovary have shown that cold stress promotes ovarian morphological alterations related to a polycystic ovary (PCO) condition through activation of the ovarian sympathetic nerves. Because the noradrenergic nucleus locus coeruleus (LC) is activated by cold stress and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway, this study aimed to evaluate the LC's role in cold stress-induced PCO in rats. Ovarian morphology and endocrine and sympathetic functions were evaluated after 8 wk of chronic intermittent cold stress (4 C, 3 h/d) in rats with or without LC lesion. The effect of acute and chronic cold stress upon the LC neuron activity was confirmed by Fos protein expression in tyrosine hydroxylase-immunoreactive neurons. Cold stress induced the formation of follicular cysts, type III follicles, and follicles with hyperthecosis alongside increased plasma estradiol and testosterone levels, irregular estrous cyclicity, and reduced ovulation. Considering estradiol release in vitro, cold stress potentiated the ovarian response to human chorionic gonadotropin. Ovarian norepinephrine (NE) was not altered after 8 wk of stress. However, LC lesion reduced NE activity in the ovary of cold-stressed rats, but not in controls, and prevented all the cold stress effects evaluated. Cold stress increased the number of Fos/tyrosine hydroxylase-immunoreactive neurons in the LC, but this effect was more pronounced for acute stress as compared with chronic stress. These results show that cold stress promotes PCO in rats, which apparently depends on ovarian NE activity that, under this condition, is regulated by the noradrenergic nucleus LC.

Noradrenaline modulates the presence of gonadotropin-releasing hormone in ovary. The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus II in rat.

“…This study shows for the first time the decrease of GnRH in the ovarian compartment in the ex vivo system, demonstrating that the peripheral nervous system with the presence of NA in the coeliac ganglion might be modulating the presence of this decapeptide, known for its apoptotic effect. The results obtained are in agreement with other authors who proposed that the increase of circulating catecholamines by a sympathetic hyperactivation [38,39] or by ganglionic stimulus at long times [25] increased the levels of ovarian E 2 . This increase together with a decrease of ovarian GnRH, observed in our study, might increase bcl-2, inhibiting apoptosis and favoring the formation of cysts in the ovary [39,40].…”

Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats

“…Ovaries, uterus, and retroperitoneal and gonadal (visceral) fat pads were weighted. Oviducts were collected bilaterally for fresh ex vivo oocyte count as described elsewhere (Bernuci et al 2008). Ovaries and attached gonadal fat pads were fixed in 4% paraformaldehyde for 24 h, and kept on 70% v/v ethanol for histological processing.…”

Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats

“…Prior reports of plasma progesterone and estradiol in rats are somewhat variable (Cameron et al, 2002;Blair and Mickelsen, 2006;Donadio et al, 2006;Jazbutyte et al, 2006;Bernuci et al, 2008). This variability may reflect differences in rat strain, the time of day and/or the particular estrous cycle phase during sampling (Freeman, 1994).…”