Title:Alleviative Effects of Adipose Tissue-derived Stem Cells and α-NETA on
Metabolic, Biochemical, and Endocrine Parameters in a Letrozole-induced Rat
Model of PCOS
Volume: 29
Issue: 24
Author(s): Hamid Reza Nejabati*, Sadeneh Nikzad and Leila Roshangar*
Affiliation:
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords:
Polycystic ovary syndrome, AdMSCs, α-NETA, chemerin, CMKLR1, ovulatory dysfunction.
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.
