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

Presently, demyelinating diseases have been reported to affect the reproductive life of patients who suffer from them, but the progression of the alterations is unknown, especially in men. To better understand these effects, it is necessary to perform studies in animal models, such as the male taiep rat, which exhibits progressive demyelination of the central nervous system, altered kisspeptin expression at the hypothalamic level, and decreased luteinizing hormone, which could alter sperm quality and testicular diameter. Thus, the objective of the present study was to analyze the diameter of the seminiferous tubules, the sperm motility, and the testosterone levels of 90-day-old male taiep rats. The obtained results indicate that male taiep rats show an increase in testicular size accompanied by an increase in the diameter of the seminiferous tubules of the left testicle. There was also a decrease in progressive motility in sperm samples from the left epididymis of male taiep rats compared to the control group, with no changes in serum testosterone concentration. Therefore, we conclude that male taiep rats with central demyelination show altered testicular diameter and decreased motility in sperm from the left side. This type of studies serves as a basis for proposing possible reproductive strategies to improve the fertility and testicular function of men with demyelinating diseases of the central nervous system.

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

Ovarian functions decrease with perimenopause. The ovary has extrinsic innervation, but the neural influence on ovarian functions and dysfunction is not well-studied. The present study aimed to biochemically and morphometrically characterize the intrinsic neurons in ovaries from young adult, middle-aged, and senescent Long Evans CII-ZV rats (3, 12, and 15 months old, respectively). Ovaries were extracted from four rats of each age group (n = 12 total), cryopreserved, and processed for immunofluorescence studies with the primary NeuN/ß-tubulin and NeuN/tyrosine hydroxylase (TH) antibodies. The soma area and number of intrinsic neurons in the ovarian stroma, surrounding follicles, corpus luteum, or cyst were evaluated. The intrinsic neurons were grouped in cluster-like shapes in ovarian structures. In senescent rats, the intrinsic neurons were mainly localized in the ovarian stroma and around the cysts. The number of neurons was lower in senescent rats than in young adult rats (p < 0.05), but the soma size was larger than in young adult rats. Immunoreactivity to TH indicated the presence of noradrenergic neurons in the ovary with the same characteristics as NeuN/ß-tubulin, which indicates that they are part of the same neuronal group. Taken together, the findings indicate that the intrinsic neurons may be related to the loss of ovarian functions associated with aging.

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

PURPOSE: 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. METHODS: Cyclic rats were subjected to left, right, or bilateral SON sectioning or to unilateral or bilateral laparotomy at diestrus 1 at 11:00 h. Animals were sacrificed 24 h after surgery. RESULTS: 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. CONCLUSIONS: At 11:00 h 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.

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

BACKGROUND: Polycystic ovary syndrome is characterized by hyperactivity of the ovarian sympathetic nervous system, increases in the content and release of norepinephrine, as well as decreases in the number of ß-adrenoreceptors. In the present study, ß-adrenoreceptors in the ovaries of rats with polycystic ovary syndrome were blocked and analyzed the resultant effects on ovulation, hormone secretion and the enzymes responsible for the synthesis of catecholamines. METHODS: At 60 days of age, vehicle or estradiol valerate-treated rats were injected with propranolol [10- 4 M] into the ovarian bursas on oestrus day. The animals were sacrificed on the next day of oestrus, and the ovulation response, the steroid hormone levels in the serum and the immunoreactivity of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovaries were measured. RESULTS: In animals with the induction of polycystic ovary syndrome and ß-adrenoreceptor blocking, ovulation was restored in more than half of the animals and resulted in decreased hyperandrogenism with respect to the levels observed in the estradiol valerate-treated group. Tyrosine hydroxylase and dopamine ß-hydroxylase were present in the theca cells of the growing follicles and the interstitial gland. Injection of propranolol restored the tyrosine hydroxylase and ovarian dopamine ß-hydroxylase levels in rats with polycystic ovary syndrome induction. CONCLUSIONS: The results suggest that a single injection into the ovarian bursas of propranolol, a nonselective antagonist of ß-adrenoreceptor receptors, decreases the serum testosterone concentration and the formation of ovarian cysts, improving the ovulation rate that accompanies lower levels of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovary.

Assuntos

RESUMO

BACKGROUND: The injection of estradiol valerate in female rats induces polycystic ovary syndrome, which is characterized by polycystic ovaries, anovulation, and hyperandrogenism. These characteristics have been associated with an increase in the ovarian concentration of norepinephrine, which occurs before establishing the polycystic ovary syndrome. The bilateral section of the superior ovarian nerve restores ovarian functions in animals with polycystic ovary syndrome. The superior ovarian nerve provides norepinephrine and vasoactive intestinal peptide to the ovary. An increase in the activity of both neurotransmitters has been associated with the development of polycystic ovary syndrome. The purpose of the present study was analyzed the participation of the noradrenergic nervous system in the development of polycystic ovary syndrome using guanethidine as a pharmacological tool that destroys peripheral noradrenergic nerve fibers. METHODS: Fourteen-day old female rats of the CIIZ-V strain were injected with estradiol valerate or vehicle solution. Rats were randomly allotted to one of three guanethidine treatment groups for denervation: 1) guanethidine treatment at age 7 to 27-days, 2) guanethidine treatment at age 14 to 34- days, and 3) guanethidine treatment at age 70 to 90- days. All animals were sacrificed when presenting vaginal oestrus at age 90 to 94-days. The parameters analyzed were the number of ova shed by ovulating animals, the ovulation rate (i.e., the numbers of ovulating animals/the numbers of used animals), the serum concentration of progesterone, testosterone, oestradiol and the immunoreactivity for tyrosine hydroxylase enzyme. All data were analyzed statistically. A p-value of less than 0.05 was considered significant. RESULTS: Our results show that the elimination of noradrenergic fibers before the establishment of polycystic ovary syndrome prevents two characteristics of the syndrome, blocking of ovulation and hyperandrogenism. We also found that in animals that have already developed polycystic ovary syndrome, sympathetic denervation restores ovulatory capacity, but it was not as efficient in reducing hyperandrogenism. CONCLUSION: The results of the present study suggest that the noradrenergic fibers play a stimulant role in the establishment of polycystic ovary syndrome.

Assuntos

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.