Effect of electroacupuncture on the kisspeptin system in a pubertal rat model of polycystic ovary syndrome

2021 ◽  
pp. 096452842097129
Author(s):  
Zhi Wang ◽  
Li Yang ◽  
Hui Dong ◽  
Haoxu Dong ◽  
Ling Cheng ◽  
...  

Objective: To explore the effects and mechanism of action of electroacupuncture (EA) in a rat model of pubertal polycystic ovary syndrome (PCOS). Methods: Female offspring of Sprague-Dawley rats receiving dihydrotestosterone (DHT) during pregnancy (days 16–19), as a model of prenatal androgenization, were divided randomly into three groups: model group (M), EA group, and sham acupuncture (SA) group (n = 8 each). A normal (N) group comprising female offspring of healthy pregnant rats not receiving DHT (n = 8) was added. EA was administered at CV6 and bilateral SP6/ST36 with 2 Hz frequency and 2 mA intensity. SA consisted of superficial needling at different locations without electrical stimulation. Results: EA improved the disturbed estrous cycles, while it could not be concluded that SA was effective in this respect. EA improved ovarian morphology including the number of corpora lutea and area of the ovary, whereas SA did not. However, both EA and SA attenuated the increased luteinizing hormone and decreased estradiol and gonadotropin-releasing hormone levels in the serum of PCOS model rats. Levels of testosterone, follicle-stimulating hormone, and progesterone did not significantly differ between groups. EA and SA alleviated the upregulation of kisspeptin protein and mRNA levels in the hypothalamus and kisspeptin protein level in the arcuate nucleus (ARC). No differences were found between groups in protein or mRNA expression of dynorphin (DYN) or neurokinin B (NKB) in the hypothalamus. Co-expression of kisspeptin, NKB, and DYN were observed in ARC. The GnRH level in the median eminence decreased and could be rescued by EA and SA. Intriguingly, kisspeptin levels in the granulosa cells of the ovary decreased in the model group and could be rescued by EA but not SA. Levels of kisspeptin, NKB, and DYN protein and mRNA in the ovary did not differ between any groups. Conclusion: Both EA and SA appeared to improve symptoms of PCOS at puberty by modulating the kisspeptin system in the hypothalamus. EA also had an effect on ovarian kisspeptin expression and a more comprehensive effect with respect to improving PCOS at puberty than SA.

2014 ◽  
Vol 998-999 ◽  
pp. 260-264
Author(s):  
Fan Wang ◽  
Yan Qing Wu ◽  
Kai Zhuan Xiao ◽  
Zheng Hong Zhang ◽  
Qing Wang ◽  
...  

Polycystic ovary syndrome (PCOS) is a major public health problem in reproductive-aged women worldwide, but the precise pathogenesis of PCOS remains unclear. Our previous study has clarified that hypoxia-inducible factor-1alpha (HIF-1α) mediated endthlin-2 (ET-2) signaling plays an important role in the ovulatory process in rats. Therefore, the present study used PCOS rat model to test the hypothesis that HIF-1α signaling is inhibited in ovaries during PCOS fromation. By the changed of bodyweight, ovarian histology and ovarian weight, PCOS rat model was further confirmed. And then the present study examined the changes of ET-2 and HIF-1α mRNA levels through real-time PCR finding the significant decrease of ET-2 mRNA level in PCOS rat ovaries was found, while HIF-1α mRNA significantly increased. However, by western blot analysis, the present study found HIF-1α protein expression was significantly decreased, which is consistent with ET-2 protein expression implying HIF-1α-medated ET-2 signaling is vital during PCOS formation. Moreover, the result of HIF prolyl hyodroxylase activity analysis found the decrease of HIF-1α protein may be caused through HIF protein degradation by the increased HIF prolyl hyodroxylase activity. Taken together, these results indicate that HIF-1α signaling is inhibited in PCOS rat model through increase of HIF prolyl hyodroxylase activity suggesting HIF-1α signaling plays an important role in the formation of PCOS. This HIF-1α-mediaged ET-2 expression may be on of the important mechanisms regulating PCOS formation in mammalian ovaries in vivo. Keywords: HIF-1α; ET-2; HIF prolyl hyodroxylase acitvity; polycystic ovary syndrome


2019 ◽  
Vol 10 (6) ◽  
pp. 645-658 ◽  
Author(s):  
Giselle Adriana Abruzzese ◽  
Maria Florencia Heber ◽  
Fiorella Campo Verde Arbocco ◽  
Silvana Rocio Ferreira ◽  
Alicia Beatriz Motta

AbstractFetal programming by androgen excess is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS is more than a reproductive disorder, as women with PCOS also show metabolic and other endocrine alterations. Since both ovarian and reproductive functions depend on energy balance, the alterations in metabolism may be related to reproductive alterations. The present study aimed to evaluate the effect of androgen excess during prenatal life on ovarian fuel sensors and its consequences on steroidogenesis. To this end, pregnant rats were hyperandrogenized with testosterone and the following parameters were evaluated in their female offspring: follicular development, PPARG levels, adipokines (including leptin, adiponectin, and chemerin as ovarian fuel sensors), serum gonadotropins (LH and FSH), the mRNA of their ovarian receptors, and the expression of steroidogenic mediators. At 60 days of age, the prenatally hyperandrogenized (PH) female offspring displayed both an irregular ovulatory phenotype and an anovulatory phenotype with altered follicular development and the presence of cysts. Both PH groups showed altered levels of both proteins and mRNA of PPARG and a different expression pattern of the adipokines studied. Although serum gonadotropins were not impaired, there were alterations in the mRNA levels of their ovarian receptors. The steroidogenic mediators Star, Cyp11a1, Cyp17a1, and Cyp19a1 were altered differently in each of the PH groups. We concluded that androgen excess during prenatal life leads to developmental programming effects that affect ovarian fuel sensors and steroidogenesis in a phenotype-specific way.


2020 ◽  
Author(s):  
Zahra Shaaban ◽  
Amin Tamadon ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Amin Derakhshanfar

Abstract Background: Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and 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, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Methods: Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on days 16-18 gestation at doses 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, and 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). Conclusions: Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.


2020 ◽  
Author(s):  
Yidong Xie ◽  
Li Xiao ◽  
Xiaohan Shi ◽  
Yifan Zhao ◽  
Xiaohong Li ◽  
...  

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity. The beneficial effects of metformin on reproduction, metabolism and endocrine, especially with the capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), place it as a good alternative for its widely prescribed, but its association with PCOS offspring remains uncertain. We aim to investigate the impact of metformin on reproductive, endocrine and metabolic characteristics in female offspring born to letrozole-induced PCOS-IR rats.Methods: 45 female wistar rats were implanted with letrozole-continuous-release pellets or placebo, subsequently treated with metformin or vehicle control, then mated with healthy male wistar rats. Estrous cycle, endocrine hormone profile, fasting insulin measurements and glucose tolerance test have been investigated and the expression of INSR in pancreas, FSHR and LHCGR in ovaries have been analyzed with Quantitative Real-time Polymerase Chain Reaction and Western Blotting assay.Results: Decreased conception rate and increased multiple pregnancy rates were found in PCOS-IR rats, which significantly improved after metformin treatment. Metformin significantly decreased the risk of body weight gain and increased INSR expression of pancreas in female F1 offspring in PCOS-IR rats. Decreased FSHR and increased LHCGR expressions in ovary were observed in female F1 rats of PCOS-IR and PCOS-IR+Met group. Nevertheless, there were no significant differences of INSR, FSHR and LHCGR expressions in female F2 offspring of PCOS-IR rats, as well as other PCOS phenotypes.Conclusions: The current study indicates that widespread reproductive, endocrine and metabolic changes in letrozole induced PCOS-IR rat model, but those PCOS phenotypes could not be inherit to offspring generations stably. Metformin may contribute to improve obesity, hyperinsulinemia and insulin resistance of female F1 offspring in PCOS-IR. The results of this study can be used as a theoretical basis for supporting metformin-using in the treatment of PCOS-IR patients.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Yu ◽  
Miao Liu ◽  
Zhenxin Wang ◽  
Te Liu ◽  
Suying Liu ◽  
...  

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear. Methods Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR. Results The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels of CYP11A and HSD17B2 were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst. Conclusion Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related to HSD17B1, CYP19A1 and CYP11A1 expression change in FF exosomes.


2011 ◽  
Vol 38 (2) ◽  
pp. 396-407 ◽  
Author(s):  
Eunkuk Park ◽  
John F. Cockrem ◽  
Kyung-Hoon Han ◽  
Doh-Hee Kim ◽  
Min-Hyung Jung ◽  
...  

2021 ◽  
Author(s):  
Hongliang Li ◽  
Yankai Guo ◽  
Gege Zhang ◽  
Jielin Deng ◽  
Hayley Fischer ◽  
...  

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