Affiliation:
1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Biology, Concordia University, Montreal, QC, Canada
Abstract
Background:
Polycystic ovary syndrome (PCOS), the most prevalent reproductive disorder, is accompanied
by hyperandrogenism (HA), ovulatory dysfunction (OD), and insulin resistance (IR). A number of
reports indicate that adipokines play a vital role in the pathophysiology of PCOS. One of these adipokines is
chemerin, which is engaged in metabolic disorders, especially obesity, diabetes, and PCOS. Based on the data,
the circulating levels of chemerin and the expression of chemokine-like receptor-1 (CMKLR1) in white adipose
tissue (WAT) of women with PCOS are significantly higher than in healthy ones. Currently, several scholars
have emphasized the therapeutic capacities of stem cells, notably mesenchymal stem cells (MSCs), for the treatment
of PCOS.
Objective:
In this study, for the first time, the impacts of 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-
NETA), an antagonist of CMKLR1, adipose-derived stem cells (ADSCs), and their combinations on metabolic
and endocrine aberrancies were assessed in the WAT and ovarian tissues of the letrozole (LET)-induced PCOS
rats.
Methods:
In the current study, 30 Wistar rats were randomly divided into five groups: control (n = 6), LET-induced
PCOS (1.5 mg/kg p.o., n = 6), LET + ADSCs (106 ADSCs i.v., n = 6), LET + α-NETA (10 mg/kg p.o., n
= 6), and LET + ADSCs + α-NETA (n = 6). The blood samples and adipose and ovarian tissues were obtained
to evaluate the effects of ADSCs and α-NETA on hormonal and metabolic parameters in the PCOS rats.
Results:
Our findings showed that the administration of α-NETA, ADSCs, and the combination of both favorably
restored the irregular estrus cycle and considerably modulated the endocrine parameters in PCOS rats. In addition,
these therapeutic factors remarkably regulated steroidogenic and adipogenic gene expressions, as well as
the genes related to glucose metabolism and brown adipose tissue (BAT) markers in these animals.
Conclusion:
These findings indicate that the combination of ADSCs and α-NETA can successfully ameliorate
metabolic and endocrine dysfunction in LET-induced PCOS rats, and this strategy could be a new therapeutic
choice for patients with PCOS.
Funder
Stem Cell Research Center of Tabriz University of Medical Sciences
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Reference57 articles.
1. Escobar-Morreale H.F.; Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018,14(5),270-284
2. Sirmans S.; Pate K.; Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013,6,1-13
3. Azziz R.; Carmina E.; Chen Z.; Dunaif A.; Laven J.S.E.; Legro R.S.; Lizneva D.; Natterson-Horowtiz B.; Teede H.J.; Yildiz B.O.; Polycystic ovary syndrome. Nat Rev Dis Primers 2016,2(1),16057
4. Nestler J.E.; Jakubowicz D.J.; de Vargas A.F.; Brik C.; Quintero N.; Medina F.; Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998,83(6),2001-2005
5. Burt Solorzano C.M.; McCartney C.R.; Blank S.K.; Knudsen K.L.; Marshall J.C.; Hyperandrogenaemia in adolescent girls: Origins of abnormal gonadotropin-releasing hormone secretion. BJOG 2010,117(2),143-149
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献