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Objective(s): One of the common heterogeneous reproductive disorders in women of childbearing age is polycystic ovary syndrome (PCOS). It is characterized by lack of fertility due to anovulatory cycles, hyperandrogenemia, polycystic ovaries, hyperinsulinemia, and obesity. Both reproductive anomalies and metabolic disorders are involved in PCOS pathology. Although the role of increased levels of androgens in initiation of PCOS is almost proven, mechanisms of PCOS pathophysiology are not clear. Here we discuss roles of altered metabolic conditions, obesity, and chronic inflammation in PCOS pathophysiology. Materials and Methods: : In this review, we attempted to identify genes related to obesity and chronic inflammation aspects of PCOS and their physiological functions to explain the pathways that are regulated by these genes and can be a prominent function in PCOS predisposition. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results: Obesity and chronic inflammation are not prominent diagnostic features of PCOS, but they play an important role in exacerbating metabolic and hyperandrogenic states. ADIPOQ, FTO TGFβ, and DENND1A as the main obesity- and chronic inflammation-related genes have roles in PCOS pathophysiology. Conclusion: It seems that genes related to obesity pathology in genomic research association, are related to metabolic aspects and body mass index in PCOS patients. Genomes have roles in chronic inflammation, followed by obesity, in the pathogenesis of PCOS. [ABSTRACT FROM AUTHOR]

Background: An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH) secretion is the most characteristics of polycystic ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide (RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods: In the experimental study, female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR) tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results: Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05). Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05). Conclusion: Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of long-term, moderate level noise exposure during crucial periods of rat infants on stereological parameters of medial geniculate body (MGB) and auditory cortex.Materials and Methods: Twenty-four male offspring of 12 pregnant rats were divided into four groups: fetal-to-critical period group, which were exposed to noise from the last 10 days of fetal life till postnatal day (PND) 29; fetal period group that exposed to noise during the last 10 days of fetal life; critical period group, exposed to noise from PND 15 till PND 29, and control group. White noise at 90 dB for 2 h per day was used.Statistical Analysis Used: Variance for variables was performed using Proc GLM followed by mean comparison by Duncan's multiple range test.Results: Numerical density of neurons in MGB of fetal-to-critical period group was lower than control group. Similar results were seen in numerical density of neurons in layers IV and VI of auditory cortex. Furthermore, no significant difference was observed in the volume of auditory cortex among groups, and only MGB volume in fetal-to-critical period group was higher than other groups. Estimated total number of neurons in MGB was not significantly different among groups.Conclusion: It seems necessary to prevent long-term moderate level noise exposure during fetal-to-critical neonatal period. [ABSTRACT FROM AUTHOR]

Objective(s): The effect of litter size and suckling intensity on the expression of KiSS-1 mRNA in the arcuate nucleus (ARC) of rats were evaluated. Materials and Methods: Thirty two pregnant and four non-lactating ovariectomized (as control group) rats were used in this experiment. Lactating rats were allotted to eight equal groups. In three groups, litter size was adjusted to 5, 10, or 15 pups upon parturition and allowed to suckle their pups continuously by 8 days postpartum. In the other three groups, litter size was adjusted to five upon birth; the pups were separated from the dams for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 2.5, 5, or 7.5 min prior to killing the dams. Two groups of lactating rats with either 10 or 15 pups were separated from their pups for 6 hr on day 8 postpartum, after which the pups were allowed to suckle their dams for 5 min before the dams were killed on day 8 postpartum. The ARC was removed and the expression of KiSS-1 mRNA was evaluated, using real-time PCR. Results: The expression of KiSS-1 mRNA in the ARC was decreased as the litter size and intensity of suckling stimulus were increased. The effect of suckling intensity on the expression of KiSS-1 mRNA was more pronounced than that of litter size. Conclusion: Increased litter size and suckling intensity decreased KiSS-1 mRNA expression in the ARC which may contribute to lactation anestrus in rat. [ABSTRACT FROM AUTHOR]

Introduction: Arginine-phenylalanine-amide-related peptide-3 (RFRP-3) is an inhibitor of gonadotropin releasing hormone (GnRH) secretion and an appetizer. Kisspeptin is a stimulator of GnRH and a regulator of energy metabolism. The objectives of the present study were to compare the effect of long term malnutrition on expression of RFRP-3 mRNA in dorsomedial hypothalamic nucleus (DMH) and KiSS-1 mRNA in arcuate nucleus (ARC) of rat hypothalamus. Methods: Sixteen female ovariectomized rats of the Sprague-Dawley strain were randomly allotted into three groups. After 2 weeks recovery period, one group was fed with perfect diet (rat standard feed) and the other group was fed with the half dietary of perfect diet for 14 days. The control group (n=4) were sacrificed 2 weeks after surgery (day 0). Relative expression of RFRP-3 and KiSS-1 mRNAs (compared to the control group) were measured using real-time PCR method in DMH and ARC of hypothalamus, respectively. Results: Mean and SE of relative expression of RFRP-3 mRNA in DMH in the half dietary rats was higher than that of the perfect diet ones (P=0.01). Relative expression of KiSS-1 mRNA in ARC was not different between two groups of rats (P=0.1). Conclusion: Long term malnutrition (2 weeks) increased RFRP-3 mRNA expression in DMH of rats hypothalamus, but had no effect on KiSS-1 mRNA expression in the ARC nucleus of ovariectomized female rats. [ABSTRACT FROM AUTHOR]

Kisspeptin and RFamide-related peptide-3 (RFRP-3) are known to affect GnRH/luteinizing hormone (LH) in several species, including the rat. It has been hypothesized that GnRH/LH changes during the rat estrous cycle may result from changes in the expression of KiSS1 and RFRP-3 genes. Therefore, the present study investigates KiSS1 and RFRP-3 gene expression at the transcriptional level in the rat hypothalamus during the estrous cycle. In the present experimental study, 36 adult female Sprague-Dawley rats (3-4 months old) were used to study the expression of KiSS1 and RFRP-3 mRNA in the hypothalamus during the estrous cycle. Four rats were ovariectomized, whereas the remainder were allotted to four different phases of the estrous cycle (n=8 per estrus phase). Rats were decapitated, and the hypothalami were immediately dissected and frozen in liquid nitrogen. Expressions of KiSS1 and RFRP-3 mRNAs were analyzed by real-time PCR. The expression of KiSS1 mRNA during estrus was lower than other phases of the cycle (p<0.01). Expression of KiSS1 mRNA during the metestrus phase was lower than the proestrus phase (p<0.01). The expression of RFRP-3 mRNA during proestrus was lower than the diestrus phase (p<0.01). Results of the present study showed the role of coordinated expression of KiSS1 and RFRP-3 mRNA in the hypothalamus in the control of the rat estrous cycle. [ABSTRACT FROM AUTHOR]

Objectives: Despite prevalence of polycystic ovary syndrome (PCOS) among childbearing women and development of many animal models for this syndrome, information on its etiology is still scarce. The intrauterine hyperandrogenic environment may underlie changes at the level of hypothalamus, pituitary, ovary organization in female offspring, and PCOS later in life. Letrozole has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, this research aimed to assess the condition in a prenatal letrozole-treated rat model., Materials and Methods: Twenty-eight female rats dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on gestation days 16-18 at doses of 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW)., Results: Prenatal letrozole treatment delayed parturition time and reduced the litter size in pregnant dams ( P <0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, serum testosterone concentration, and reduced estradiol levels ( P <0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, letrozole at 1.25 and 1 mg/kg BW showed increased RFRP and decreased GnRH mRNA expression ( P <0.0001). Letrozole treatment at doses of 1 mg/kg BW and lower was not fetotoxic., Conclusion: It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins- and steroid hormones-related genes., Materials and Methods: Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review., Results: In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSHβ, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG , and their effects in PCOS of human have been confirmed., Conclusion: Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic-pituitary-ovarian axis disturbances, respectively., Competing Interests: There are no conflicts of interest.

Objectives: To benefit from reproduction and deal with challenges in the environmental conditions, animals must adapt internal physiology to maximize the reproduction rate. Maladaptive variations in the neurochemical systems and reproductive system can lead to manifestation of several significant mammalian reprocesses, including mammalian ovarian lifespan. RFamide-related peptide (RFRP, Rfrp), mammalian orthologues of gonadotropin-inhibitory hormone (GnIH), which is a regulator to prevent the gonadotropin-releasing hormone (GnRH) neural activity, is known to be related to reproductive traits. This review aimed to summarize recent five-year observations to outline historic insights and novel perspectives into the functions of RFRPs in coding the mammalian reproductive physiology, especially highlight recent advances in the impact on RFRPs in regulating mammalian ovary lifespan., Materials and Methods: We reviewed the recent five-year important findings of RFRP system involved in mammalian ovary development. Data for this review were collected from Google Scholar and PubMed using the RFRP keyword combined with the keywords related to physiological or pathological reproductive functions., Results: Recent discoveries are focused on three major fronts in research on RFRP role in female reproduction including reproductive functions, energy balance, and stress regulation. The roles of RFRPs in various development phases of mammal reproduction including prepuberty, puberty, estrous cycle, pregnancy, milking, menopause, and/or ovarian diseases have been shown., Conclusion: Overall, these recent advances demonstrate that RFRPs serve as critical mediators in mammalian ovarian development.

Until 2000 it was believed that gonadotropin-releasing hormone (GnRH) was the sole regulator of hypophyseal gonadotropes. In 2000, the discovery of a gonadotropin inhibitory hormone (GnIH) initiated a revolution in the field of reproductive physiology. Identification of GnIH homologues in mammals, the arginine-phenylalanine-amide (RFamide)-related peptides (RFRPs), indicated a similar function. Subsequently, further works conducted in various laboratories worldwide have shown that these neuropeptides inhibit the hypothalamic-hypophyseal axis. This review discusses the role of RFRPs in mammalian reproductive processes.

Background: RFamide-related peptide-3 (RFRP-3) inhibits gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in rats. This study evaluates the effects of litter size and suckling intensity on RFRP mRNA expression in the dorsomedial hypothalamic nucleus (DMH) of rats., Materials and Methods: A total of 32 pregnant and 4 non-lactating ovariectomized (control group) Sprague-Dawley rats were used in this experimental study. Lactating rats were allotted to 8 equal groups. In 3 groups, the litter size was adjusted to 5, 10, or 15 pups upon parturition. Dams were allowed to suckle their pups continuously until 8 days postpartum. In the other 3 groups, the litter size was adjusted to 5 pups following birth. These pups were separated from the dams for 6 hours on day 8 postpartum, after which the pups were allowed to suckle for 2.5, 5, or 7.5 minutes prior to killing the dams. In 2 groups, lactating rats with 10 and 15 pups were separated from their pups for 6 hours on day 8 postpartum. In these groups, the pups were allowed to suckle their dams for 5 minutes before the dams were killed. All rats were killed on day 8 postpartum and the DMH was removed from each rat. We evaluated RFRP mRNA expression using realtime polymerase chain reaction (PCR)., Results: The expression of RFRP mRNA in the DMH increased with increased litter size and suckling intensity compared to the controls. The effect of suckling intensity on the expression of RFRP mRNA was more pronounced compared to the litter size., Conclusion: Increased litter size and suckling intensity stimulated RFRP mRNA expression in the DMH which might contribute to lactation anestrus in rats.

Background: RFamide-related peptide-3 (RFRP-3) and kisspeptin (KiSS-1) are known to respectively inhibit and stimulate gonadotropin releasing hormone (GnRH) and lute- inizing hormone (LH) secretion in rat. The aim of the present study was to evaluate the relative mRNA expression of RFRP-3 and KiSS-1 in the hypothalamus of pregnant rats., Materials and Methods: In a randomized controlled experimental study, the exact preg- nancy day of 18 Sprague-Dawley rats were confirmed using the vaginal smear method and were equally assigned to three groups of days 7, 14 and 21 of pregnancy. Four non- pregnant female rats were ovariectomized and assigned as the control group. All rats were decapitated, and the dorsomedial hypothalamic nucleus (DMH) and the arcuate nucleus (ARC) for detection of KiSS-1 mRNA were separated from their hypothalamus to detect RFRP-3 and KiSS-1 mRNA respectively. Then, their relative expressions were compared between control and pregnant groups using real-time polymerase chain reac- tion (PCR)., Results: The relative expression of RFRP-3 mRNA in DMH did not change significantly during pregnancy (p>0.01). However, the relative expression of KiSS-1 mRNA in ARC was at its highest in day 7 of pregnancy and decreased until day 21 of pregnancy (p<0.01)., Conclusion: Decrease in GnRH and LH secretion during the pregnancy of rat may be controlled by constant expression of RFRP-3 mRNA and reduced expression of KiSS-1 mRNA in hypothalamus.

The aims of the present study were to evaluate luteal activity in Abadeh ecotype goat during summer and winter and also the effect of a single dose kisspeptin-10 injection on the secretion of luteinizing hormone (LH) in female anestrous goats. In the first study, progesterone (P4) concentration in 10 goats in summer (n = 6) and winter (n = 4) were measured every other day. Moreover, in summer group, a male teaser goat was left in the herd on days of sampling for one hour. Goats with P4 concentration ≥1 ng mL(-1), at least two consecutive measurements, were considered with luteal activity. In the second study, the anestrous phase was confirmed by P4 measurement 20 and 10 days before the kisspeptin injection in five female Abadeh ecotype goats (4 to 5 years old). The goats were given a single IV injection of saline (2 mL) as control group and the same goats (1 hr after the last blood sampling) were given kisspeptin (1 μg kg(-1)) as treatment group. The blood samples were collected at -60, -40, -20 and 0 min (before injection), and 10, 20, 30, 40, 50, 60, 80, 100, 120 and 140 min after the injection and LH concentration were measured. A single IV injection of 1 µg kg(-1) of kisspeptin-10 did not stimulate the release of LH in female anestrous goats. In summer, in the presence of teaser goat, luteal activity was seen in all goats. In the absence of male goat in winter, some goats showed luteal activity and others showed anestrus.