RESUMO

Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic-pituitary-ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 µL of saline solution as vehicle or with 0.225 µg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 µL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.

RESUMO

Ovarian functions are modulated by the hypothalamus-pituitary-ovary axis and neural signals. Stress modifies the activity of the sympathetic nervous system. In adult female rats, cold stress results in higher noradrenergic and steroidogenic activity of the ovary, anovulation and the presence of ovarian cysts; however, it is unknown whether this response occurs in prepubertal rats. The purpose of this study was to analyse the effects of cold stress initiated in the prepubertal stage of female rats on ovarian function. Female rats 24 days old were exposed to three, five or eight weeks of cold stress. Autopsies were performed at the end of each stress period. The parameters analysed were the number of ova shed by ovulating animals; the number of ovulating animals; the serum concentrations of progesterone, testosterone, and oestradiol; and the ovarian concentrations of norepinephrine and 3-methoxy-4-hydroxyphenyl-glycol. Our results show that chronic cold stress applied to prepubertal rats did not modify the number of ovulating animals, the total number of ova shed, or progesterone and testosterone concentrations in any of the periods analysed. Oestradiol concentration was lower in the animals exposed to five or eight weeks of stress. The ovarian norepinephrine concentration was higher in the animals exposed to three weeks of stress and was lower at eight weeks of stress. No changes in ovarian morphology were observed. Our data suggest that the changes in noradrenergic activity resulting from chronic cold stress experienced in the prepubertal stage do not modify ovarian architecture or affect the ovulatory response in adulthood.

Assuntos

RESUMO

In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.

Assuntos

RESUMO

In rats with polycystic ovarian syndrome (PCOS) induced by estradiol valerate (EV) injection, sectioning of the vagus nerve in the juvenile stage restores ovulatory function, suggesting that the vagus nerve stimulates the onset and development of PCOS. We analyzed whether in adult rats, the role played by the vagus nerve in PCOS development is associated with the nerve's regulation of noradrenergic activity in the celiac superior mesenteric ganglion (CSMG). Ten-day-old rats were injected with corn oil [vehicle (Vh)] or EV (2 mg). At 76 days of age, rats injected with Vh or EV were subjected to sham surgery or the sectioning of one or both vagus nerves (vagotomy). The animals were sacrificed at 80-82 days of age at vaginal estrus smear. Compared to Vh-treated animals, EV-induced PCOS rats showed a lack of ovulation, the presence of follicular cysts, and a high concentration of testosterone, without changes in noradrenaline concentrations in the CSMG or ovaries. In PCOS rats, sham surgery lowered serum testosterone and noradrenaline concentrations in the CSMG but did not restore ovulation. In animals with PCOS, vagotomy lowered testosterone concentrations to a larger degree than in sham-surgery animals. The ovaries of rats with PCOS and vagotomy showed fresh corpora lutea, indicating ovulation. In EV-treated rats with unilateral vagotomy, the concentration of noradrenaline in the CSMG was similar to that in rats with PCOS and sham surgery, which did not ovulate, while in the ovaries of PCOS rats with left or bilateral vagotomy, the noradrenaline concentration was lower than that in sham-surgery-treated animals. Our results suggest that the vagus nerve regulates PCOS development through a different mechanism than the increase in the noradrenergic activity in the CSMG; however, in ovaries, the restoration of ovulation is associated with a decrease in ovarian noradrenaline.

RESUMO

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.

RESUMO

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.

Assuntos