Section Of Superior Ovarian Nerve Research Articles

Unilateral section of the superior ovarian nerve induces first ovulation in the Zucker fatty (fa/fa) rat

Hyperactivity in the sympathetic nervous system has been shown to be related to the development of ovarian pathologies. In addition, obesity has been found to be associated with multiple reproductive anomalies and is considered a chronic stress condition of low intensity with changes in the peripheral sympathetic activity. Therefore, in the present study, we aimed to evaluate if the information reaching the ovaries through the superior ovarian nerve (SON) modifies the ovarian function of Zucker fatty rats. We performed a unilateral section of the SON at 32 days of age and autopsies were carried out on the day of the first vaginal estrus. The results showed that fatty animals do not ovulate on the day of the first vaginal estrus and exhibit an increase in catecholaminergic fibers and the presence of precystic structures in the ovaries, without changes in the onset of puberty or in the secretion of ovarian and hypophyseal hormones. We also found that the section of the right SON resulted in ovulation on the day of the first vaginal estrus, which was accompanied by a decrease in ovarian noradrenaline content. The section of the left SON caused a delay in puberty without changes in the rest of the parameters. These results provide functional evidence that the peripheral sympathetic innervation participates in the regulation of ovarian functions in an animal model of genetic obesity.

Role of the superior ovarian nerve in the regulation of follicular development and steroidogenesis in the morning of diestrus 1.

Little is known about the role of the superior ovarian nerve (SON) in follicular development during the estrus cycle. The aim of the present study was to analyze the role of neural signals arriving through the SON at the ovaries in the regulation of follicular development and ovarian steroid secretion in diestrus 1 of cyclic rats. Cyclic rats were subjected to left, right, or bilateral SON sectioning or to unilateral or bilateral laparotomy at diestrus 1 at 11:00h. Animals were sacrificed 24h after surgery. Compared to laparotomized animals, unilateral SON sectioning decreased the number of preovulatory follicles, while bilateral SON sectioning resulted in a decreased number of atretic preantral follicles. An important observation was the presence of invaginations in the follicular wall of large antral and preovulatory follicles in animals with denervation. Furthermore, left SON sectioning increased progesterone levels but decreased testosterone levels, which are effects that were not observed in animals that were subjected to right denervation. At 11:00h of diestrus 1, the SON was found to stimulate follicle development, possibly via neural signals, such as noradrenaline and/or vasoactive intestinal peptide, and this stimulation induced the formation of follicle-stimulating hormone receptors. The role of the SON in the regulation of ovarian steroid secretion is asymmetric: the left SON inhibits the regulation of progesterone and stimulates testosterone secretion, and the right nerve does not participate in these processes.

The Neural Signals of the Superior Ovarian Nerve Modulate in an Asymmetric Way the Ovarian Steroidogenic Response to the Vasoactive Intestinal Peptide.

The superior ovarian nerve (SON) provides neuropeptide-Y, norepinephrine and vasoactive intestinal peptide (VIP) to the ovaries. Ovarian steroidogenesis is modulated by the SON. In the cyclic rat, the acute steroidogenic response to ovarian microinjection of VIP is asymmetric and varies during the estrous cycle. In the present study, we analyze whether the differential effects of VIP in each ovary are modulated by the neural signals arriving through the SON. Cyclic female rats were submitted on diestrus-1, diestrus-2, proestrus, or estrus to a unilateral section of the SON, and immediately afterward, the denervated ovary was either microinjected or not with VIP. Animals were sacrificed 1 h after treatment. The injection of VIP into the left denervated ovary performed on diestrus-1 decreased progesterone levels in comparison with the left SON sectioning group; similar effects were observed on proestrus when VIP was injected into either of the denervated ovaries. Compared to the left SON sectioning group, VIP treatment into the left denervated ovary on diestrus-2 or proestrus decreased testosterone levels, whereas on diestrus-1, proestrus or estrus, the same treatment resulted in higher estradiol levels. Compared to the right SON sectioning group, VIP injected into the right denervated ovary yielded higher testosterone levels on diestrus-1 and estrus and lower testosterone levels on proestrus. VIP injection into the right denervated ovary increased estradiol levels on diestrus-2 or estrus while decreasing them on proestrus. Our results indicate that in the adult cyclic rat, the set neural signals arriving to the ovaries through the SON asymmetrically modulate the role of VIP on steroid hormone secretion, depending on the endocrine status of the animal. The results also support the hypothesis that the left and right ovary respond differently to the VIPergic stimulus.

Sympathetic innervation regulates macrophage activity in rats with polycystic ovary

Polycystic ovarian syndrome (PCOS) is a low-grade inflammatory disease characterized by hyperandrogenism and ovarian hyperinnervation. The aim of this work is to investigate whether in vivo bilateral superior ovarian nerve (SON) section in adult rats with estradiol valerate-induced PCOS (PCO rats) affects macrophage spleen cells (MФ) and modifies the steroidogenic ability of their secretions. Culture media of MФ from PCO rats and PCO rats with SON section (PCO-SON rats) were used to stimulate in vitro intact ovaries. Compared with macrophages PCO, macrophages from PCO-SON rats released less tumor necrosis factor-α and nitric oxide, expressed lower Bax and Nfkb mRNA and showed reduced TUNEL staining. Also, in PCO rats, the SON section decreased kisspeptin and nerve growth factor mRNA expressions, without changes in Trka receptor mRNA levels. Macrophage secretions from PCO-SON rats decreased androstenedione and stimulated progesterone release in PCO ovaries, compared to macrophage secretions from PCO rats. No changes were observed in ovarian estradiol response. These findings emphasize the importance of the SON in spleen MΦ, since its manipulation leads to secondary modifications of immunological and neural mediators, which might influence ovarian steroidogenesis. In PCO ovaries, the reduction of androstenedione and the improvement of progesterone release induced by PCO-SON MΦ secretion, might be beneficial considering the hormonal anomalies characteristic of PCOS. We present functional evidence that modulation of the immune-endocrine function by peripheral sympathetic nervous system might have implications for understanding the pathophysiology of PCOS.

Both the Suprachiasmatic Nucleus and the Superior Ovarian Nerve Contribute to the Processes of Ovulation and Steroid Hormone Secretion on Proestrus

The aims of the present study were to analyze if the superior ovarian nerve (SON) plays a role in the neural signals from suprachiasmatic nucleus (SCN) that lead to ovulation and ovarian steroids secretion on proestrus day. Rats on proestrus day were treated at 11.00 to 11.30 or 17.00 to 17.30 hours with 1 of the 3 experimental procedures (1) unilateral or bilateral SON sectioning, (2) unilateral or bilateral injury to the SCN, or (3) unilateral injury to the SCN followed by unilateral sectioning of the SON ipsilateral to the treated SCN. Treatments were evaluated 24 hours after surgical procedures. Compared to laparotomized animals, right or bilateral SON sectioning treatment at 17.00 hours resulted in lower ovulation rates and number of ova shed by the right ovary. The ovaries of nonovulating animals showed early follicular luteinization signs and trapped ova. Bilateral SCN injury treatment at 11.00 hours resulted in anovulation; whereas right SCN injury treatment, with or without right SON sectioning, resulted in a lower number of ova shed. Injecting luteinizing hormone-releasing hormone to animals with bilateral SCN injury restored ovulation. In rats with unilateral or bilateral SON sectioning, or with injury to the SCN with or without unilateral sectioning of the SON, the effects on hormone levels depended of the hormone studied and the time of day treatment was performed. The present results suggest that on proestrus day, the role of the right or both SON in ovulation and steroid hormone secretion regulation takes place through different neuroendocrine mechanisms from SCN.

In the pubertal rat, the regulation of ovarian function involves the synergic participation of the sensory and sympathetic innervations that arrive at the gonad.

BackgroundThe present study investigates sectioning the superior ovarian nerve (SON) in rats with functional sensorial denervation induced by capsaicin administration at birth and the effects on the establishment of puberty, ovulation, serum progesterone, and estradiol concentrations.MethodsThe animals were allotted randomly to one of the following experimental groups. Groups of 8–10 rats were injected at birth with capsaicin or vehicle, and on day 20 or 28 of life, they were submitted to a sham operation (SO). Other groups of 8–10 rats were injected at birth with capsaicin or vehicle, and on day 20 or 28 of life, they were submitted to the uni-or bilateral SON sectioning. The animals were killed at the first estrus. Serum concentration of progesterone (ng/ml) and estradiol (pg/ml) were measured using a radioimmunoassay.ResultsAnimals treated with capsaicin and subjected at 20 days of life to the left or bilateral section of SON had a delayed age of vaginal opening. Furthermore, animals with a lack of sensory information and subjected to a SO at 28 days of life had the same delay in the age of vaginal opening. Animals with sensorial innervation intact, subjected to unilateral section of the SON at 20 or 28 days of age, showed diminished ovulation rate and number of ova shed by the denervated ovary. In animals with sensorial denervation, the uni-or bilateral sectioning of the SON did not result in changes in ovulation. Progesterone and estradiol levels were different depending on the age of the animal in which the SON section was performed.ConclusionsBased on the present results, we suggest that sympathetic innervation regulates ovulation and the secretion of steroid hormones and that the sensory fibers modulate the sympathetic innervation action on ovarian functions.

Effect of Secretion of Splenocytes after Superior Ovarian Nerve Section on the Ovarian Steroidogenesis

It is known that ovary and spleen are innervated extensively by afferent and efferent noradrenergic sympathetic nerve fibers from the celiac ganglion. Furthermore, immune cells located in the ovary influence the ovarian physiology. However, the peripheral interaction between the immune and neuroendocrine system is poorly understood. This work was undertaken to study the effect of superior ovarian nerve (SON) transection, in adult rats, on the number of splenocyte β-adrenergic receptors and their possible relation to ovarian steroidogenesis, measuring the effect of secretions of those splenocytes on progesterone and estradiol release from the ovary. Seven days after SON transection, the splenocytes were isolated and then cultured for 48 h. Their number of β-adrenergic receptors, measured using [¹²⁵I]-cyanopindolol as ligand, increased, and their culture media, used to stimulate ovaries from 60-day-old intact (neither SON-transected nor sham-operated) rats in vitro on diestrous day 2 showed a decrease in progesterone release and an increase in estradiol release in relation to splenocyte culture media of control rats (sham-operated; p < 0.001, respectively). The effects of in vivo SON transection were simulated by an in vitro system modulating the splenocyte β-adrenergic receptor number. The splenocytes from SON-transectioned rats were preincubated with and without norepinephrine (NE) 10^–6 M for 48 h, a low and high number of β-adrenergic receptors respectively, and then were stimulated with NE 10^–6 M for 24 h. After that, the culture medium from splenocytes with a low number of β-adrenergic receptors induced progesterone release from the ovaries of intact rats (p < 0.001), but produced no change in estradiol release. The data suggest that splenocyte secretions, which participate in the ovarian steroidogenic response, particularly in progesterone release, might be controlled by adrenergic influences since the number of splenocyte β-adrenergic receptors changes through SON-celiac ganglion-noradrenergic postganglionic innervation of the spleen. In estradiol release, probably other neurotransmitters than norepinephrine (NE) are involved when the SON is sectioned. In this paper we also show functional evidence for modulation of immune function by the sympathetic nervous system and its principal neurotransmitter, NE.

Involvement of the pelvic plexus and the suprarenal ganglia in the neuropeptide Y (NPY) innervation of the cervix and the uterus of the rat

The involvement of the pelvic plexus and suprarenal ganglia in the neuropeptide Y (NPY) innervation of the genital tract was studied in the female rat by means of denervation experiments and retrograde tracing studies. Removal of the paracervical ganglia caused a significant decrease of the NPY-immunoreactive nerve density and NPY concentration in the lower part of the genital tract: cervix, uterine body and lower part of the uterine horn. The decrease in NPY concentration in these three regions was more pronounced after lesion of the pelvic plexus. Lesion of the ovarian nerve plexus caused a depletion in the NPY-immunoreactive nerve fibres and a decrease in NPY concentration in the upper part of the uterine horn. Pelvic nerve section, inferior mesenteric ganglia excision and superior ovarian nerve section had no effect on the NPY innervation in the genital tract. Injection of fluorogold into the cervix and lower part of the uterus combined with immunohistochemistry revealed that 87.5% of labelled neurons in the pelvic plexus were NPY-immunoreactive. Following injection of fluorogold into the upper part of the uterus, 92% of labelled neurons in the suprarenal ganglia were NPY-immunoreactive. Treatment with 6-hydroxydopamine revealed that the NPY-immunoreactive nerve fibres were non-noradrenergic in the cervix, but were noradrenergic in the upper part of the uterus. In the uterine body and lower part of the uterine horn, both noradrenergic and non-noradrenergic NPY-immunoreactive nerve fibres were observed. These data demonstrate the major contribution of pelvic plexus neurons in the non-noradrenergic NPY innervation of the lower part of the genital tract, and the involvement of the suprarenal ganglia in the noradrenergic NPY innervation of the upper part of the uterus via the ovarian nerve plexus.

Participation of the superior ovarian nerve in the regulation of compensatory ovarian hypertrophy: the effects of its section performed on each day of the oestrous cycle.

The effects were analysed of secretion of the superior ovarian nerve on compensatory ovulation and ovarian hypertrophy, in adult rats with the left or right ovaries extirpated during the oestrous cycle and autopsied 6 or 20 days later. Rats with hemiovariectomy or hemiovariectomy plus denervation recovered their oestrous cyclicity between 2 and 3 days after surgery. Six days after hemiovariectomy 14 out of 17 rats ovulated on the expected day of oestrus. All the animals were hemiovariectomized on the day of pro-oestrus. The mean +/- S.E.M. number of ova shed was similar to the group of animals with both ovaries (7.8 +/- 1.2 vs 9.5 +/- 0.2). Compensatory ovarian hypertrophy was observed in the right ovary when left hemiovariectomy was performed on day 2 of dioestrus or pro-oestrus; similar results were observed in the left ovary when the right one was extirpated at oestrus or pro-oestrus. Section of the right superior ovarian nerve in left-hemiovariectomized rats caused a reduction in ovulation rate and number of ova released. Compensatory ovarian hypertrophy was modified in the opposite way by unilateral section of the superior ovarian nerve to the in situ ovary depending on the day of the cycle when hemiovariectomy was performed. Twenty days after treatment, ovulation rate, compensatory ovulation and ovarian hypertrophy were similar in both left- or right-hemiovariectomized rats. Compensatory ovarian hypertrophy increased in all animals with section of the superior ovarian nerve, except when hemiovariectomy was carried out at oestrus or the left ovary was extirpated on day 1 of dioestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of ovarian sympathetic innervation in the control of estrous responsiveness in the rat

This study examined the contribution of the superior ovarian nerve (SON) to estrous responsiveness and ovarian function in cycling rats. Section of the SON was carried out at 1100 on proestrus, and lordotic responsiveness was measured at 1500, 1700, and 2100 on that day and at 0900, 1200, and 1500 on the day of estrus. SON section decreased lordosis intensity significantly at 1500 and 1700 on proestrus and at 0900 on estrus. Pacing of sexual contacts with males was decreased at 2100 in nerve-sectioned (Nervx) animals when compared with sham-operated controls (SHAM). Serum progesterone (P) concentrations were significantly lower in Nervx animals than in Sham animals 30 min after surgery, but were not different between groups at 4.5 hr. Serum estradiol (E 2) concentrations did not differ between groups at either time. In addition, Nervx and Sham groups did not differ on measures of pregnancy/pseudopregnancy initiation or on measures of ovarian function 10 days after surgery. These data suggest that the integrity of the SON is necessary for the display of full estrous responsiveness in cycling rats, and suggest that the acute decreases in serum P occurring as a consequence of SON section may be responsible for the deficits seen in Nervx animals.

Ovarian Adrenergic Nerves Directly Participate in the Control of Luteinizing Hormone-Releasing Hormone and β-Adrenergic Receptors during Puberty: A Biochemical and Autoradiographic Study

The rat ovary receives sympathetic innervation from the superior ovarian nerve (SON) and the plexus nerve (OP). To examine the possibility of a direct adrenergic mechanism controlling ovarian receptor distribution during the onset of puberty, we have studied the acute (48-h) effect of unilateral nervotomy (combined section of SON and OP nerves) on ovarian LHRH and beta-adrenergic receptor concentrations and distribution using both radioreceptor assays and in vitro autoradiography. Ovarian LHRH receptor concentration increased sharply between 12 and 20 days of age. At this time receptors were mostly associated with follicles and interstitial cells, whereas at 37 days of age, when a measurable loss in the receptor concentration was observed, light and diffuse autoradiographic labeling of receptors was also found in the corpora lutea. Complete removal of adrenergic input to the gland produced a sharp decrease in LHRH-binding activity within the denervated ovary at each time interval studied, with no effect in the innervated contralateral gland. Autoradiographic data also revealed a decrease in both the number of labeled follicles and the intensity of the labeling. beta-Adrenergic receptor concentration increased progressively between days 12 and 27, reaching a peak value at 37 days of age. Labeling was very weak at 12 days of age and increased progressively at 20 and 27 days of age. At this time, receptors were mostly localized by autoradiography in the interstitial cells, while at 37 days of age corpora lutea were strongly labeled. Ovarian beta-adrenergic receptors showed a marked drop when acutely deprived of their neural tone, as illustrated by the 2- to 3-fold decrease in receptor-binding capacity within the denervated gland. The autoradiographic data also showed marked changes in beta-adrenergic receptor distribution, specially at 37 days of age. At this time, the labeling of corpora lutea was markedly decreased in denervated ovaries. The present results clearly demonstrate that complete removal of ovarian adrenergic tone produces a profound decrease in the concentrations of LHRH and beta-adrenergic receptors within the ovary, although it cannot be excluded that peptidergic factors also arriving via the SON and OP could have some influence on the regulation of these receptors. The results support the concept of a direct involvement of the central nervous system in ovarian function. They also suggest that during ovarian development a neural efferent system might be involved in the adjustment of ovarian responsiveness to stimulation by the gonadotropins via changes in receptor content and/or distribution in the different ovarian compartments.

Ovarian adrenergic nerves play a role in maintaining preovulatory steroid secretion.

Little is known about the role of ovarian nerves in the control of steroid secretion. We have examined the effect of sectioning the adrenergic superior ovarian nerve (SON) on the secretion of progesterone (P), and estradiol (E2) from the ovary. The steroids were measured in blood samples collected every 4 min from the ovarian vein in the proestrous and estrous phases of the rat estrous cycle. Upon section of the nerve at 1100 h of proestrus, secretion of both steroids dropped within 4 min and remained at about 50-60% of presection values for the rest of the sampling period. At 1600 h of proestrus, systemic plasma LH was elevated and P output was markedly increased. SON section produced a transient (8-min) decrease in P levels, but E2 concentrations remained depressed. Section of the SON during estrus failed to alter the output of either steroid. SON section did not alter blood flow. It is suggested that neural impulses, possibly adrenergic, which reach the ovary via the SON contribute to the maintenance of gonadotropin-supported secretion of ovarian steroids on the day of proestrus. The results are consistent with the view that, in addition to its hormonal regulation, the ovary is directly controlled by the central nervous system (CNS) through specific neural pathways.

Prepubertal ovarian function is finely regulated by direct adrenergic influences. Role of noradrenergic innervation.

In the rat, the main source of adrenergic fibers innervating nonvascular ovarian tissue is the superior ovarian nerve (SON). To determine the influence of the SON on prepubertal ovarian function and, hence, on the time of puberty, several experiments were conducted. Transection of the SON in early juvenile rats (day 24) led to more than 60% depletion in ovarian norepinephrine (NE) content, but affected neither the timing of vaginal opening nor that of first ovulation. SON section, however, produced a 2-fold increase in beta-adrenergic receptor density, with no change in affinity, suggesting that hypersensitivity by denervation had developed. Removal of all adrenergic influences from ovarian granulosa cells by culturing the isolated cells in vitro produced a striking increase in beta-adrenergic receptor number, which was maximal at 72 h. In spite of this elevated receptor content, the beta-adrenergic agonist Zinterol did not induce progesterone release unless the cells were previously exposed for 48 h to a physiological concentration of FSH. Both NE and epinephrine down-regulated the receptors in a dose-related manner, without affecting receptor affinity. To test the hypothesis that denervation of the ovary results in greater steroidal sensitivity to adrenergic stimulation, a model was constructed in which cells were simultaneously exposed to FSH and NE or epinephrine (innervated cells) or exposed only to FSH (denervated cells) for 48 h. The response to adrenergic stimulation was subsequently measured by incubating the cells with Zinterol for 24 h. Zinterol was highly effective in eliciting progesterone release from the denervated cells, but failed to do so in innervated cells. Additionally, the agonist increased cAMP in the former cells, but it was ineffective in the latter, indicating that prior exposure to catecholamines desensitized the adenyl cyclase enzyme coupled to beta-adrenergic receptor sites. The results suggest that during prepubertal maturation, noradrenergic fibers reaching the ovary via the SON may modify ovarian steridogenic sensitivity to catecholamines, by regulating the number of functional beta-adrenergic receptors in the gland. They also indicate that the apparent failure of SON denervation to alter the maturation of ovarian steroidogenesis and the time of puberty may be due to development of compensatory hypersensitivity after the denervation.