Immunological detection of Platelet-derived growth factor and Vascular endothelial growth factor in Iraqi women with Polycystic Ovarian Syndrome

 

Zainab Ali Hlail¹, Khalil Ismail Abid Mohammed², Ahmed Sahib Abd-ulamir³,

Mohammed Odah Salman⁴

¹College of Anesthesia Techniques, Al-Farahidi University, Baghdad, Iraq.

²College of Medicine, University of Baghdad, Baghdad, Iraq.

³College of Medicine, Al-Nahrain University, Baghdad, Iraq.

⁴High Institute of infertility Diagnosis and Assisted reproductive technology(ART),

Al-Nahrain University, Baghdad, Iraq.

 

ABSTRACT:

Background: platelet-derived growth factor (PDGF) signaling controls a wide range of the mesenchymal cell origin lineages throughout the development and in the females with the polycystic ovarian syndrome. Vascular endothelial growth factor (VEGF) has an important impact on vascularization of the tissues generally, and in pathogenesis of a wide range of the illnesses. The PCOS has been found related to high VEGFexpression levels. Aims and Objectives: for the detection and studying of immunological effects of PDGF and VEGF in the Iraqi females with the PCOS. Materials and Methods: 250 Iraqi females, aged between 20 and 50 years have been divided to twogroups, which are: study group (n=125, PCOS) and control group (n=125, which mainly consisted from normal females), the samples of the blood have been obtained in 2^ndmenstruate cycle day, VEGF and PDGF concentrations have been estimated for every one of the groups. Results: the PCOS patients have shown a considerable difference in comparison to the other group. The level has been 71.22±65.23Pg/ml and 243± 153.44Pg/ml, for the controls and PCOS patients respectively. In addition to that, the PCOS patients have shown a considerable difference in comparison to the other group. . The level has been 71.22±65.23Pg/ml and 243± 153.44Pg /ml, for the controls and PCOS patients respectively. Conclusions: Increases concentration of PDGF and VEGF in PCOS women related to ovulation lack and that lead to increases the risk of PCOS appearance.

 

 

INTRODUCTION:

The PDGF signaling path-way is responsible for the regulation of several lineages of the mesenchymal cell origins throughout the development years as well as during adulthood. Transcriptional targets of this path-way were found to be needed in a number of the PDGF-dependent procedures, however, the roles of those targets in certain tissue types are just starting to be identified^1,2.

 

In previous study, it has been shown that 5 different target genes of the PDGF are vital for the fertility of the women. The mutations in every one of those 5 different genes result in causing defects in steroid-producing cells in ovaries and changed levels of the hormone productions, which suggest that the pathway of the PDGF regulates the steroid genesis through those genes in the two genders, not the females alone. In addition to that, the conditional mutations of the two receptors of the PDGF have shown a requirement in the steroid-producing cells in several organs, which include ovaries, testes, as well as the adrenal cortex. Which is why, the PDGF signallingcould constitute a typical mechanism in controlling multiple steroidgenic lineages^3,4.

 

VEGF has a significant impact on the vascularization of the tissues. In the females undergoing the assisted reproductive technology, the VEGF has been found as one of key mediators of the other factors for controlling the angiogenesis of the ovaries.^5,6,7

 

VEGF system is made up of the ligands and the receptors in the tissue vascularization as well as the endothelial cell growth^8,9). It has been stated as well to result in the induction of the proliferation of the cells, inhibition of the apoptosis, promotion of the migration of the cells, and induction of blood vessels’ permeabilization. It’s one of the main components of angiogenic factors’ family, including the angiopoetin, placental growth factor, basic fibroblast growth factor and VEGF group (A, B, C, D and E) .^10,11

 

VEGF particularly, is a protein that is encoded by the gene (Gene ID: 7422) which is located in the chromosome 6 and extended on over 16kb (GRCh37/hg19; chr6: 43737946– 43754224). The gene includes 8 exons and encodes for several of the isoforms of VEGF as VEGF-165 and VEGF-145. Earlier researches have stated that there has been a correlation of the VEGFA gene with the PCOS through SNP +9812, +13553, −2578 (rs699947), −460 (rs833061) and +405 and their haplotypes in different origin           populations^{12,13, 14}.

 

In addition to that, the SNPs +405 and −460 have been reported to have a trend toward higher levels of insulin resistance. The impact of some of those SNPs on regulating VEGF gene expression and protein secretion and production has been suggested¹⁵.

 

MATERIALS AND METHODS:

There have been 250 women cases researched, they were aged 20 and 50 years, they have been divided to two equal groups, the first one included PCOS, whereas the second group consisted of normal women and was referred to as the control group. The samples have been obtained in the 2^nd day of the menstrual cycle; VEGF and PDGF have been concentrated with the use of the ELISA approach.

 

RESULTS:

PDGF level has showed significant a considerable in the PCOS patients in comparison with control. The level was 243±153.44 (Pg /ml), 71.22± 65.23Pg /ml for PCOS patients and controls respectively. The level that ranges between 0 and 668Pg/ml, as listed table1.

 

Table1: PDGF levels in PCOS patient’s and controls

Serum PDGF (Pg /ml)	Numbers	Mean	Standard Deviation	P-values
Patients	125	243	153.44	<0.0001
Controls	125	71	65.23

The serum level of the VEGF showed considerable differences between the PCOS patients and controls (P<0.05). The level was 203±148.07 (Pg/ml), 74.16± 83.84Pg/ml in the PCO Sand controls respectively. The level ranges between 0 and 581pg/ml, Table 2.

 

Table 2: VEGF value of PCOS and control groups involved in the study

 

The receiver Operator characteristic curve for PDGF and VEGF is shown in table 3.

 

Table 3: The receiver Operator characteristic curve (ROC) for control and polycystic ovarian syndrome in term of PDGF and VEGF

 

DISCUSSION:

The PCOS can be defined as clinically important not due to the reduced fertility, but also due to the long term cardiovascular and metabolic diseases. The PCOS is typically characterized by the hirsutism, polycystic ovaries, and anovulation. Usually, the PCOS is adversely influenced by obesity, insulin confrontation, and dyslipidemia; in addition to that, it poses a significant risk for the development of metabolic squeal and cardio-vascular, including diabetes and metabolic syndrome. PDGF level had shown significant differences in the patients with PCOS in comparison with control group. The level was 243±153.44 (Pg/ml), 71.22±65.23Pg /ml for PCOS patients and control group respectively. The level was ranged between 0 and 668 Pg/ml.

 

The present study showed high level of PDGF in PCOS patients in comparison with control group (P<0.0001). These results are in disagreement with previous studies which indicated that the level of PDGF decreases in PCOS women ¹⁶, the reason for the difference may be due to the different types of PDGF studied in the studies or because of the day on which the sample was taken. The PDGFs play several vital roles in the normal embryonic development, responses to tissue damage and cellular differentiation. The changes that have been noticed in PDGF are form levels could result in the prevention of the VEGF-induced vascular permeability in PCOS ovaries through the regulation of the levels of the endothelial-cell-junction protein. Restorations of the angiogenic fact or levels could be providing new information about the treatment of PCOS as well as prevention of the ovarian hyperstimulation syndrome in the affected female patients. ^{17, 18}

 

Serum level of the VEGF has shown considerable differences between the PCOS patients and controls (P<0.05). The level has been 203±148.07Pg /ml, 74.16± 83.84Pg/ml in the PCOS and the controls respectively. The level was ranged between 0pg/ml and 581pg/ml.

 

The human VEGF, which has been considered as the most prominent and potent one of the angiogenic factors in the vascular permeability and cyclic angiogenesis, results in the stimulation of the endothelial proliferation, survival and migration. A number of the researches had shown that the increase in the ovarian vascularity is correlated with the increase in the levels of the serum VEGF in PCOS patients.^19,20

 

In a research that has been carried out by Loebig et al, 2010²¹, authors have shown that there is a positive association between concentration of the serum VEGF and a high level of the body mass index (BMI) ranging between 17.6kg/m² and 43.6kg/m² in the controls²¹.

 

The follicle stimulating hormone (FSH) results in the increase of the expression of the VEGF from 9mm to 12mm follicles, and eventually the luteinizing hormone (LH) results in the promotion of the expression of the VEGF from more mature preovulatory follicles. At the selection of the follicles, the FSH- and consequently LH-induced production of VEGF improve the angiogenesis within theca layer, facilitating the rapid growth of the preovulatory follicles.^22,23,24

 

ACKNOWLEDGMENTS:

The authors express their gratefulness to the College of Medicine, Univ. of Baghdad, Iraq and Al-Farahedi University.

 

FUNDING:

There have not been any funding sources.

 

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Accepted on 11.03.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(10):4526-4528.