ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2018, 3(3): 25–29
https://doi.org/10.26693/jmbs03.03.025
Experimental Medicine and Morphology

The Condition of the Rats' Endometrium and Ovaries during Experimental Modeling of the Polycystic Ovary Syndrome in Terms of Constant Cold Exposure

Kuzmina I. Yu., Zhulikova M. V.
Abstract

Polycystic ovary syndrome (PCOS) is characterized by a violation of reproductive and menstrual function and is due to a number of factors. The main factors are: increased production of androgens, insulin resistance and disruption of the regulation of reproduction hormones. The purpose of this work was to study the morphometric parameters of the endometrium and ovary of rats in terms of constant cold exposure (CCE) and experimental PCOS modeling by introducing dehydroepiandrosterone (DHEA). Material and methods. Studies were performed on female Wistar rats (n = 32) of 27-day-old age, weighing 30-40 g. The polycystic process in the ovaries was modeled by daily (for 25 days) subcutaneous administration of DHEA ("Sigma", USA) dissolved in 0.2 ml of purified and sterilized olive oil. The dose of DHEA was 60 mg / kg of body weight. CCE was carried out by daily keeping the animals for 4 hours in a chamber where the light regime and the temperature of + 4° C were maintained. The remaining 20 h animals were in normal conditions of detention. Animals were divided into 4 groups: the 1st group – animals that were exposed to CCE (n = 8); the 2nd group – animals were treated with DHEA (n = 8) with CCE; the 3rd group 3 – animals who were challenged with experimental PCOS by the administration of DHEA (n = 8); the 4th group – intact control (n = 8). On the 26th day the animals were sacrificed, the uterus and ovaries were taken. The organs were weighed and then fixed in 4% paraformaldehyde (PFA, "Sigma") for 4 hours, after that they were transferred for 12 hours to a 25% sucrose solution on phosphate buffered saline. Results and discussion. Results indicate that the exogenous introduction of androgens into the body of experimental animals leads to hyperplasia of the thecal cells as a characteristic feature of PCOS. The obtained data suggest that in terms of cold exposure, the secretion of endogenous androgens by the adrenals is activated, which leads to a slight hyperplasia of the thecal ovarian tissue cells. Endometrium is a mucous membrane lining the uterine cavity, which reacts to cyclic changes in estrogen and progesterone in the menstrual cycle of the ovaries. The follicular (proliferative) phase of the endometrium is associated with the growth of the follicle in the ovary and the increased secretion of estrogens. In PCOS, in the absence of ovulation and regulation through progesterone secreted by the yellow body, the endometrium is constantly exposed to the mitogenic effects of estrogens, which leads to its proliferation. Microscopic examination of uterine tissue in a group of rats with a PCOS model (Group 3) showed an increase in the height of the endometrial epithelium, the number of glands and the thickening of the uterine wall. In the group with PCOS simulation in terms of CCE, as in the group with CCE, these indicators were at the level of intact control. Visually, the histological pattern in the groups of rats with PCOS differed from the other groups and was characterized by an increase in the number of glands and with expansion of their lumens. Conclusions. The introduction of DHEA to young rats during 25 days leads to the appearance of PCOS characteristics symptoms in the ovaries and uterus: thickening of the cells layer, decrease in the number of yellow bodies, the appearance of cysts, thickening of the uterine wall and endometrial hyperplasia. Stimulation of adaptive physiological reactions in terms of prolonged cold effects blocks the development of PCOS signs in rats with the administration of DHEA.

Keywords: morphometric characteristics, rat endometrium, polycystic ovary syndrome, cold exposure

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References
  1. Lebbe M, Woodruff TK. Involvement of androgens in ovarian health and disease. Mol Hum Reprod. 2013 Dec; 19 (12): 828-37. https://www.ncbi.nlm.nih.gov/pubmed/24026057. https://www.ncbi.nlm.nih.gov/pmc/articles/3843026. https://doi.org/10.1093/molehr/gat065
  2. Silfen ME, Denburg MR, Manibo AM, Lobo RA, Jaffe R, Ferin M, Levine LS, Oberfield SE. Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J Clin Endocrinol Metab. 2003 Oct; 88 (10): 4682-8. https://www.ncbi.nlm.nih.gov/pubmed/14557441. https://doi.org/10.1210/jc.2003-030617
  3. Groth SW. Adiponectin and polycystic ovary syndrome. Biol Res Nurs. 2010 Jul; 12 (1): 62-72. https://www.ncbi.nlm.nih.gov/pubmed/20498127. https://www.ncbi.nlm.nih.gov/pmc/articles/3646519. https://doi.org/10.1177/1099800410371824
  4. Yuan X, Hu T, Zhao H, Huang Y, Ye R, Lin J, Zhang C, Zhang H, et al. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. Proc Natl Acad Sci USA. 2016 Mar 8; 113 (10): 2708-13. https://www.ncbi.nlm.nih.gov/pubmed/26903641. https://www.ncbi.nlm.nih.gov/pmc/articles/4790997. https://doi.org/10.1073/pnas.1523236113
  5. Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig. 2016 Apr 1; 26 (1): 25-42. https://www.ncbi.nlm.nih.gov/pubmed/26910750. https://doi.org/10.1515/hmbci-2015-0073
  6. Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010 Nov; 1212: E1-E19. https://www.ncbi.nlm.nih.gov/pubmed/21276002. https://www.ncbi.nlm.nih.gov/pmc/articles/3075414. https://doi.org/10.1111/j.1749-6632.2010.05875.x
  7. van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest. 2013 Aug; 123(8): 3395-403. https://www.ncbi.nlm.nih.gov/pubmed/23867626. https://www.ncbi.nlm.nih.gov/pmc/articles/3726172. https://doi.org/10.1172/JCI68993
  8. Jankovic A, Korac A, Buzadzic B, Otasevic V, Stancic A, Vucetic M, Markelic M, Velickovic K, Golic I, Korac B. Endocrine and metabolic signaling in retroperitoneal white adipose tissue remodeling during cold acclimation. J Obes. 2013; 2013: 937572. https://www.ncbi.nlm.nih.gov/pubmed/23710349. https://www.ncbi.nlm.nih.gov/pmc/articles/3655592. https://doi.org/10.1155/2013/937572
  9. Zhang Y, Hu M, Meng F, Sun X, Xu H, Zhang J, Cui P, Morina N, Li X, et al. Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome. EBioMedicine. 2017 Apr; 18:157-70. https://www.ncbi.nlm.nih.gov/pubmed/28336389. https://www.ncbi.nlm.nih.gov/pmc/articles/5405166. https://doi.org/10.1016/j.ebiom.2017.03.023
  10. Will MA, Palaniappan M, Peegel H, Kayampilly P, Menon KM. Metformin: direct inhibition of rat ovarian theca-interstitial cell proliferation. Fertil Steril. 2012 Jul; 98 (1): 207-14. https://www.ncbi.nlm.nih.gov/pubmed/22608319. https://www.ncbi.nlm.nih.gov/pmc/articles/3389190. https://doi.org/10.1016/j.fertnstert.2012.04.010
  11. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016 Oct; 37 (5): 467-520. https://www.ncbi.nlm.nih.gov/pubmed/27459230. https://www.ncbi.nlm.nih.gov/pmc/articles/5045492. https://doi.org/10.1210/er.2015-1104
  12. Shah B, Parnell L, Milla S, Kessler M, David R. Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol. 2010 Jun; 23 (3): 146-52. https://www.ncbi.nlm.nih.gov/pubmed/19733099. https://doi.org/10.1016/j.jpag.2009.07.002
  13. Mirabolghasemi G, Kamyab Z. Changes of The Uterine Tissue in Rats with Polycystic Ovary Syndrome Induced by Estradiol Valerate. Int J Fertil Steril. 2017 Apr-Jun; 11 (1): 47-55. https://www.ncbi.nlm.nih.gov/pubmed/28367305. https://www.ncbi.nlm.nih.gov/pmc/articles/5215711