scholarly journals Polycystic ovary rat model exposure to 150 kHz intermediate frequency: hypothalamic-pituitary-ovarian axis at the receptor, cellular, tissue, and hormone levels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Stephanie Mohammed ◽  
Venkatesan Sundaram ◽  
Chalapathi R. Adidam Venkata ◽  
Nikolay Zyuzikov
Keyword(s):  
Treatment Option ◽  
Arcuate Nucleus ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Intermediate Frequency ◽  
Cellular Tissue ◽  
Female Rats ◽  
Whole Body ◽  
Polycystic Ovaries ◽  
Invasive Treatment

Abstract Introduction The hypothalamic-pituitary-ovarian (HPO) axis is the principal regulator of the reproductive system. The neurons in the arcuate nucleus of the hypothalamus signal the basophilic cells of the anterior pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH), which bind to the granulosa and theca cells of a follicle in the ovary to promote healthy follicular development. Disruption of this process at any time can lead to polycystic ovaries and, if left untreated, can lead to Polycystic Ovarian Syndrome (PCOS), one of the leading causes of infertility. A novel treatment option using 150 kHz Intermediate Frequency (IF) Electromagnetic Radiation (EMR) has been proposed to monitor the effect of this frequency during cystic development. Methods To prove this, an experiment was conducted to study the effect of whole-body exposure to 150 kHz EMR for 8 weeks at receptor, cellular, tissue and hormonal levels on the HPO axis of 25 young cyclic female rats. Results The results showed that 150 kHz EMR did not affect the histoarchitecture of neurons of arcuate nucleus of the hypothalamus of PCO-induced rats. It was also found that the number of basophilic cells of the pituitary gland was increased and the immunoreactivity of LH and FSH secretion increased. This EMR field also decreased the development of follicular cysts in the ovary and possibly increased the immunoreactivity of the LH and FSH receptors as well on the theca and granulosa cells of follicles in the ovary. Conclusion There are still many limitations to this study. If properly evaluated, the results of this experiment could help develop a new non-invasive treatment option for women with PCOS in the near future.

scholarly journals A New Rat Model Exhibiting Both Ovarian and Metabolic Characteristics of Polycystic Ovary Syndrome

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3781-3791 ◽  
Author(s):  
Louise Mannerås ◽  
Stefan Cajander ◽  
Agneta Holmäng ◽  
Zamira Seleskovic ◽  
Theodore Lystig ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Structural Changes ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Continuous Administration ◽  
Metabolic Characteristics ◽  
Theca Interna

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a “hyperplastic” theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.

scholarly journals Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

2018 ◽  
Author(s):  
Pedro J. Torres ◽  
Bryan S. Ho ◽  
Pablo Arroyo ◽  
Lillian Sau ◽  
Annie Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Treatment Option ◽  
Gut Microbiome ◽  
Polycystic Ovary ◽  
Causal Role ◽  
Rrna Gene ◽  
Potential Treatment ◽  
Polycystic Ovaries ◽  
Microbial Composition ◽  
Metabolic Dysregulation

AbstractPolycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 10% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo/anovulation and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A co-housing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Since mice are coprophagic, co-housing results in repeated, non-invasive inoculation of gut microbes in co-housed mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole-treated mice co-housed with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we observed that the gut microbial composition of letrozole-treated mice co-housed with placebo mice differed from letrozole mice housed together. In addition, our analyses identified several bacterial taxa including Coprobacillus, Dorea and Adlercreutzia associated with the improved PCOS phenotype in letrozole-treated mice co-housed with placebo mice. These results indicate that disruption of the gut microbiome may play a causal role in PCOS and that manipulation of the gut microbiome may be a potential treatment option for PCOS.SignificancePCOS is a common cause of female infertility and ~80% of women with PCOS have metabolic dysregulation that predisposes them to type 2 diabetes and cardiovascular disease. Since treatment options for the metabolic symptoms of PCOS are limited, there is a need to develop novel therapeutic options. The gut microbiome has emerged as an important player in human health and has been shown to play a causal role in obesity. In this study, we found that exposure to a healthy gut microbiome through co-housing protected against the development of reproductive and metabolic dysregulation in a PCOS mouse model. These results suggest that manipulation of the gut microbiome may be a potential treatment option for women with PCOS.

Scanning Electron Microscopy of the Polycystic Ovary in Constant Light Rats

1981 ◽  
Vol 39 ◽  
pp. 538-539
Author(s):  
K. B. Singh ◽  
F. K. Khosho
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Polycystic Ovary ◽  
Three Dimensional ◽  
Continuous Light ◽  
Female Rats ◽  
Constant Light ◽  
Sprague Dawley ◽  
Polycystic Ovaries ◽  
Scanning Electron

Exposure of female rats to continuous light eventually induces persistent estrus (PE), a syndrome which in many respects resembles the human polycystic ovary syndrome. Light microscopic studies on the polycystic ovaries of constant light PE rats have been previously reported. In the present study, we have utilized scanning electron microscopy (SEM) to provide information regarding three-dimensional changes occurring on the surface of the polycystic ovary.Following exposure to continuous light for 50 days, PE was induced in a group of Sprague-Dawley female rats according to the procedure described elsewhere (2). Polycystic ovaries from constant light PE rats and ovaries from controls were fixed in 2.5% glutaraldehyde in 0.1M Na cacodylate buffer, pH 7.3 at room temperature for 24 hours. They were then cut into two equal halves along their long axis and fixed for an additional 3-4 hours. The specimens were processed for SEM studies by a modified OTOTO technique, dehydrated and critical point dried with CO2.

Exposure to 1800 MHz GSM- like radiofrequency electromagnetic field reduces follicular development and overall fertility of female rats

2015 ◽  
Vol 5 (4) ◽  
pp. 127-136
Author(s):  
Ali S. H. Alchalabi ◽  
Erkihun Aklilu ◽  
Abd Rahman Aziz ◽  
F. Malek ◽  
S. H. Ronald ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Follicular Development ◽  
Reproductive Activity ◽  
Female Rats ◽  
Whole Body ◽  
Control Group ◽  
Sprague Dawley ◽  
Activity Impairment ◽  
Sprague Dawley Rats ◽  
Radiofrequency Electromagnetic Field

  In the current study, the effect of 1800 MHz radiofrequency radiation exposure on female rats’ fertility was investigated. The study was conducted on the nine groups of female Sprague-Dawley rats (20 rats/group) with a control group and exposure groups which exposed to EMF 1hr/day and 2hr/day for 15, 30 and 60 days respectively. Animals were whole-body exposed using a GSM-like radiofrequency generator at SAR level 0.048 W/Kg. After the last exposure, rats were divided into two subgroups for fertility evaluation, ovari-an follicle count, and oxidative stress assessment. Prolonged cohabitation day until delivery in exposure groups animals compared to control was ob-served. Moreover, a significant decrease in the number of pups per delivery was observed. Ovarian follicle count showed a dramatic decrease in exposure groups throughout the experiment except the number of atretic follicles was significantly increased compared to control groups. FSH level was signifi-cantly reduced within exposure groups. LH level remained constant except in 2hr. /day group for 60 days. Melatonin levels were significantly lower in ex-posure groups. Glutathione peroxidase activity was reduced in most exposure groups. Malondialdehyde levels were raised significantly in most expo-sure groups compared to the control. Our findings conclude that exposure to electromagnetic field's cause female reproductive activity impairment.

scholarly journals 5α-dihydrotestosterone treatment induces metabolic changes associated with polycystic ovary syndrome without interfering with hypothalamic leptin and glucocorticoid signaling

2016 ◽  
Vol 68 (3) ◽  
pp. 473-481
Author(s):  
Marina Nikolic ◽  
Natasa Velickovic ◽  
Ana Djordjevic ◽  
Biljana Bursac ◽  
Djuro Macut ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Day Treatment ◽  
Reproductive Age ◽  
Female Rats ◽  
Leptin Resistance ◽  
Polycystic Ovaries ◽  
Metabolic Disturbances ◽  
Inflammatory Signaling ◽  
Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogenous disorder, with hyperandrogenism, chronic anovulation and polycystic ovaries as basic characteristics, and associated metabolic syndrome features. Increased secretion of leptin and leptin resistance are common consequences of obesity. Leptin is a hormone with anorexigenic effects in the hypothalamus. Its function in the regulation of energy intake and consumption is antagonized by glucocorticoids. By modulating leptin signaling and inflammatory processes in the hypothalamus, glucocorticoids can contribute to the development of metabolic disturbances associated with central energy disbalance. The aim of the study was to examine the relationship between hypothalamic leptin, glucocorticoid and inflammatory signaling in the development of metabolic disturbances associated with PCOS. The study was conducted on an animal model of PCOS generated by a continual, 90-day treatment of female rats with 5?-dihydrotestosterone (DHT). The model exhibited all key reproductive and metabolic features of the syndrome. mRNA and/or protein levels of the key components of hypothalamic glucocorticoid, leptin and inflammatory pathways, presumably contributing to energy disbalance in DHT-treated female rats, were measured. The results indicated that DHT treatment led to the development of hyperphagia and hyperleptinemia as metabolic features associated with PCOS. However, these metabolic disturbances could not be ascribed to changes in hypothalamic leptin, glucocorticoid or inflammatory signaling pathways in DHT-treated rats.

scholarly journals Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

2016 ◽  
Vol 113 (10) ◽  
pp. 2708-2713 ◽  
Author(s):  
Xiaoxue Yuan ◽  
Tao Hu ◽  
Han Zhao ◽  
Yuanyuan Huang ◽  
Rongcai Ye ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Brown Adipose Tissue ◽  
Polycystic Ovary ◽  
Specific Treatment ◽  
Whole Body ◽  
Sham Operation ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Brown Adipose

Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS.

scholarly journals Hyperactive LH Pulses and Elevated Kisspeptin and NKB Gene Expression in the Arcuate Nucleus of a PCOS Mouse Model

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Lourdes A Esparza ◽  
Danielle Schafer ◽  
Brian S Ho ◽  
Varykina G Thackray ◽  
Alexander S Kauffman
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Arcuate Nucleus ◽  
Polycystic Ovary ◽  
Pulse Frequency ◽  
Polycystic Ovaries ◽  
Lh Pulsatility ◽  
Hypothalamic Arcuate Nucleus ◽  
Technical Advances

Abstract Polycystic ovary syndrome (PCOS), a common reproductive disorder in women, is characterized by hyperandrogenemia, chronic anovulation, cystic ovarian follicles, and luteinizing hormone (LH) hyper-pulsatility, but the pathophysiology isn’t completely understood. We recently reported a novel mouse model of PCOS using chronic letrozole (LET; aromatase inhibitor). Letrozole-treated females demonstrate multiple PCOS-like phenotypes, including polycystic ovaries, anovulation, and elevated circulating testosterone and LH, assayed in “one-off” measures. However, due to technical limitations, in vivo LH pulsatile secretion, which is elevated in PCOS women, was not previously studied, nor were the possible changes in reproductive neurons. Here, we used recent technical advances to examine in vivo LH pulse dynamics of freely moving LET female mice versus control and ovariectomized (OVX) mice. We also determined whether neural gene expression of important reproductive regulators such as kisspeptin, neurokinin B (NKB), and dynorphin, is altered in LET females. Compared to controls, LET females exhibited very rapid, elevated in vivo LH pulsatility, with increased pulse frequency, amplitude, and basal levels, similar to PCOS women. Letrozole-treated mice also had markedly elevated Kiss1, Tac2, and Pdyn expression and increased Kiss1 neuronal activation in the hypothalamic arcuate nucleus. Notably, the hyperactive LH pulses and increased kisspeptin neuron measures of LET mice were not as elevated as OVX females. Our findings indicate that LET mice, like PCOS women, have markedly elevated LH pulsatility, which likely drives increased androgen secretion. Increased hypothalamic kisspeptin and NKB levels may be fundamental contributors to the hyperactive LH pulse secretion in the LET PCOS-like condition and, perhaps, in PCOS women.

scholarly journals Correction to: Neuroendocrine characteristics of induced pluripotent stem cells from polycystic ovary syndrome women

2019 ◽  
Vol 11 (3) ◽  
pp. 227-229
Author(s):  
Zheying Min ◽  
Yue Zhao ◽  
Jing Hang ◽  
Yun Ren ◽  
Tao Tan ◽  
...  
Keyword(s):  
Embryoid Body ◽  
Polycystic Ovary ◽  
Low Frequency ◽  
Follicular Development ◽  
Polycystic Ovaries ◽  
Atp Production ◽  
Follicular Maturation ◽  
Supplementary Material ◽  
Induced Pluripotent ◽  
High Level

In the original publication the Fig. 2 and the Supplementary Material 1 was incorrect. The correct version of Fig. 2 and the Supplementary Material are provided in this correction article. NESTIN should be corrected to PAX6 in Fig. 2C legend and at page 528 and Supplementary Material 1. NANOG should be corrected to PAX6 in Fig. 2C picture. Fig. 2. Differentiation and identification of NSCs from PCOS-derived iPSCs. (A) Schematic procedure of NSCs differentiation from iPSCs. NSC: Neural stem cell; EB: embryoid body. (B) The phenotype of specific differentiated NSCs. Scale bars = 100 µm. (C) Immunofluorescence images of the NSC markers SOX2 and PAX6. Scale bars = 50 µm. ZOOM, scale bars = 25 μm. (D) The mitochondrial respiration function of PCOS- and non-PCOS-derived iPSCs and NSCs. (E) Quantitative analysis of basal oxygen consumption, ATP production, maximal respiration, and proton leak. (F) Proposed neuroendocrine state in normal and PCOS patients. In normal patients, the GnRH pulsatile frequency is critical for steroidogenesis and follicular development. Low frequency pulses prefer FSH, and high frequency pulses favour LH. In PCOS, the increased GnRH release led to a high level of LH pulsatility, impairing the preferential release of FSH and follicular maturation, thus leading to polycystic ovaries. Red: increased; Blue: decreased. Solid arrow: up regulated; Dotted arrow: down regulated.

scholarly journals Enhancement of Melanocortin-4 Receptor (MC4R) and Constancy of Kiss1 mRNAs Expression in the Hypothalamic Arcuate Nucleus in a Model of Polycystic Ovary Syndrome Rat

2018 ◽  
Vol 7 ◽  
pp. e1070
Author(s):  
Mohammad Hossein Nooranizadeh ◽  
Farhad Rahmanifar ◽  
Somayeh Ahmadloo ◽  
Zahra Shaaban ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Arcuate Nucleus ◽  
Polycystic Ovary ◽  
Continuous Light ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
And Control

Background: Hypothalamic Melanocortin-4 Receptor (MC4R) and kiss1/kisspeptin systems play roles in reproductive processes. This study was conducted to evaluate changes in MC4R and kiss1 genes expression in the arcuate nucleus (ARC) of the hypothalamus and its relationship with polycystic ovary syndrome (PCOS) in rats.Materials and Methods: In the current experimental study, 24 female rats were randomly and equally allocated into nulliparous and primiparous groups and then were divided into two subgroups of PCOS and control. PCOS was induced by exposure to continuous light. Sex-related hormones were evaluated by radioimmunoassay or immunoradiometric assay. Expressions of MC4R and kiss1 gene in the ARC of the hypothalamus of the rats were evaluated by real-time PCR. Histomorphometric alterations of ovaries were compared between groups.Results: Number of tertiary follicles and their size and number of atretic follicles in the PCOS subgroups were more than those in the controls (P<0.05) whereas the number of secondary follicles and corpus luteum in the PCOS subgroups were lower than those in the controls (P<0.05). Antrum and total diameters of tertiary follicles in the PCOS subgroups were greater and granulosa layer diameter was lower than those in the controls (P<0.05). The MC4R mRNA expression in the PCOS subgroups was 6.5-fold in nulliparous and 3.5-fold in primiparous groups more than their controls’ pairs (P<0.05). However, parity did not affect the expression of MC4R gene (P>0.05).The kiss1 mRNA expression in the PCOS and control subgroups was not significantly different (P>0.05).Conclusion: Overexpression of MC4R gene after PCOS induction in the ARC of the hypothalamus may link to metabolic disorders of induced PCOS in the rats. However, alteration in the kiss1 mRNA expression after PCOS induction was not observed in the rats. [GMJ.2018;7:e1070]

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

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