Abstract
Sympathetic innervation of the ovary in rodents occurs via two routes: the superior ovarian nerve (SON), which runs along the ovarian ligament, and the plexus nerve (PN), which is mainly associated with the vasculature. SON and ovarian norepinephrine (NE) levels play a major role in regulating ovarian cystic health. Although it was previously described that the polycystic ovarian phenotype (PCO) is causally related to hyperstimulation of the sympathetic nerves of the ovary, much less is known, however, regarding the role of PN in ovarian physiology. We studied the role of SON and PN in relation to the maintenance of the PCO phenotype induced in the rat by exposure to estradiol valerate (EV). EV exposure at 24 days old (juvenile exposure) increases NE in the ovary for up to 90 days after EV injection. SON or PN denervation (SONX and PNX) decreased NE. SONXreversed the acyclic condition from 30 days after surgery (p < 0.05), but PNXdid not. SONX was more effective than PNX to downregulate the increased number of cysts induced by EV, with the presence of the corpora lutea (CL, signifying ovulation) in the SONX group. Seventy percent of SONX rats presented with pregnancy at 60 days post-EV (6 of the 7 sperm-positive rats were pregnant); however, SONX rats had a reduced number (half) of pups compared with vehicle-treated rats and 60% more pups than EV rats. These data suggest that the SON plays a predominant role in follicular development, ovulation and pregnancy during ovarian diseases.
Highlights
Gonadotropins from hypothalamus-pituitary glands regulate ovarian function
PNX and SONX denervation was effective in decreasing the NE concentration after 30 days of surgery, but it was recovered after 60 days post-nerve transection (Figure 1)
We studied the contribution of the plexus nerve (PN) and superior ovarian nerve (SON) in the control of ovary function and fertility
Summary
Gonadotropins from hypothalamus-pituitary glands regulate ovarian function. recent evidence points to neural regulation of the ovary with neurotransmitter release from the sympathetic nerve endings regulating ovarian follicular health (Curry et al, 1985; Lara et al, 1993; Stener-Victorin et al, 2008). The second group of nerves, the plexus nerve (PN) is associated with the vasculature, and the fibers enter the ovary through the hilum It is not known if the PN regulates steroid secretion and follicular development (Lara et al, 2002). Evidence comes from animal models of PCOS where the administration of estradiol valerate (EV) to rats increases norepinephrine (NE) concentration in the ovary and is associated with the development of the polycystic phenotype with absent estrous cycling and reduced corpus lutea In this model, surgical denervation of the SON decreased ovarian NE, and, intriguingly, the rat recovers estrous cycling activity and increases corpus luteal numbers (Brawer et al, 1986; Barria et al, 1993). Since such information does not exist for PN, we designed two experimental procedures: (1) We blocked the estradiol-induced increase in the sympathetic tone of the ovary by local surgical denervation of the SON (SONX) or PN (PNX) to test whether we can discriminate between nerves to recover follicular development and ovulation after denervation. (2) Since SON is postulated to regulate steroid secretion, we tested the impact of SON on fertility upon mating
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