Berna DİLBAZ, Betül DÜNDAR, Ümit GÖKTOLGA, Ömer Lütfi TAPISIZ, Burcu GÜNDOĞDU, Kamil Hakan MÜFTÜOĞLU, Serkan Barış MÜLAZIMOĞLU

What is the impact of PPAR-γ agonist-rosiglitazone on ovarian reserve after hysterectomy? An experimental study

Background/aim: To evaluate the effects of hysterectomy on rat ovaries and the possible protective role of peroxisome proliferatoractivated receptor gamma (PPAR-γ) agonist-rosiglitazone against ovarian reserve decrement. Materials and methods: Forty-five adult Wistar albino rats were randomly divided into three groups. Hysterectomy was performed (n = 15) in group 1 [H]; 1 mg/kg/day PPAR-γ agonist/rosiglitazone was used for 50 days after hysterectomy (n = 15) in group 2 [H + R]; a sham operation was performed (n = 15) in group 3 [control, C]. Blood samples were collected for anti-Müllerian hormone (AMH) evaluation in all groups and simultaneous ovarian Doppler examination was performed in [H] and [H + R] groups before and after (50 days) hysterectomy. All animals were sacrificed to obtain ovaries for histological examination. Results: AMH levels were found to be significantly decreased at postoperative day 50 in all groups (P < 0.05). Histopathologic analysis showed that primary, preantral, and antral follicle counts were significantly higher in the [H] group as compared to the [C] and [H + R] groups (P < 0.05). There was no significant difference between the [C] and [H + R] groups in terms of follicle numbers (P > 0.05). In the ovarian Doppler blood flow analysis, all parameters were significantly decreased in group [H] (P < 0.05), but not in the [H + R] group (P > 0.05) on postoperative day 50. Conclusion: Hysterectomy affects the histopathological structure of rat ovaries and PPAR-γ agonist-rosiglitazone improves the ovarian Doppler blood flow parameters.

PDF

___

1. Oldenhave A, Jaszmann LJ, Everaerd WT, Haspels AA. Hysterectomized women with ovarian conservation report more severe climacteric complaints than do normal climacteric women of similar age. American Journal of Obstetrics and Gynecology 1993; 168 (3 Pt 1): 765-771. doi: 10.1016/s0002-9378(12)90816-9
2. Ranney B, Abu-Ghazaleh S. The future function and fortune of ovarian tissue which is retained in vivo during hysterectomy. American Journal of Obstetrics and Gynecology 1977; 128 (6): 626-634. doi: 10.1016/0002-9378(77)90208-3
3. Chalmers C, Lindsay M, Usher D, Warner P, Evans D et al. Hysterectomy and ovarian function: levels of follicle stimulating hormone and incidence of menopausal symptoms are not affected by hysterectomy in women under age 45 years. Climacteric 2002; 5 (4): 366-373.
4. Vuorento T, Maenpaa J, Huhtaniemi I. Follow-up of ovarian endocrine function in premenopausal women after hysterectomy by daily measurements of salivary progesterone. Clinical Endocrinology (Oxf) 1992; 36 (5): 505-510. doi: 10.1111/j.1365- 2265.1992.tb02253.x
5. Hallqvist Everhov A, Bergmark K, Smedby KE, Lindén Hirschberg A, Flöter Rådestad A. Anti-Müllerian hormone in premenopausal women following treatment of uterine cervical cancer. Acta Obstetricia et Gynecologica Scandinavica 2014; 93 (9): 949-953. doi: 10.1111/aogs.12448
6. Moorman PG, Myers ER, Schildkraut JM, Iversen ES, Wang F et al. Effect of hysterectomy with ovarian preservation on ovarian function. Obstetrics and Gynecology 2011; 118 (6): 1271-1279. doi: 10.1097/AOG.0b013e318236fd12
7. Ware J. Measures for a New Era of Health Assessment. In: Stewart ALWJ, editor. Measuring Functioning and Well-Being: The Medical Outcomes Study Approach. Durham, NC: Duke University Press; 1992. pp. 3-11.
8. Mondul AM, Rodriguez C, Jacobs EJ, Calle EE. Age at natural menopause and cause-specific mortality. American Journal of Epidemiology 2005; 162 (11): 1089-1097. doi: 10.1093/aje/ kwi324
9. Wilson LF, Pandeya N, Byles J, Mishra GD. Hysterectomy and perceived physical function in middle-aged Australian women: a 20-year population-based prospective cohort study. Quality of Life Research 2018; 27 (6): 1501-1511. doi: 10.1007/s11136- 018-1812-9
10. Laganà AS, Vitale SG, Nigro A, Sofo V, Salmeri FM et al. Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives. International Journal of Molecular Sciences 2016; 17 (7). doi: 10.3390/ijms17070999
11. Aksakal O, Yilmaz B, Gungor T, Sirvan L, Sut N et al. A randomised controlled trial on melatonin and rosiglitazone for prevention of adhesion formation in a rat uterine horn model. Archives of Gynecology and Obstetrics 2010; 282 (1): 55-61. doi: 10.1007/s00404-009-1240-8
12. Komar CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function--implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reproductive Biology and Endocrinology 2005; 3: 41. doi: 10.1186/1477-7827-3-41
13. Yamakawa K, Hosoi M, Koyama H, Tanaka S, Fukumoto S et al. Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells. Biochemical and Biophysical Research Communications 2000; 271 (3): 571-574. doi: 10.1006/ bbrc.2000.2665
14. Waynforth HB. Experimental and surgical technique in rat. Cambridge, MA, USA: Academic Press; 1992.
15. Tapisiz OL, Gungor T, Aytan H, Zergeroglu S, Mulazimoglu B et al. Does hysterectomy affect ovarian function? Histopathologic evaluation and serum FSH, inhibin A, and inhibin B levels in an experimental rat model. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2008; 140 (1): 61-66. doi: 10.1016/j.ejogrb.2008.04.001
16. Aslan M, Kucukaslan I, Mulazimoglu S, Soyer T, Şenyücel M et al. Quantitative software analysis of ultrasonographic textures in experimental testicular torsion. European Journal of Pediatric Surgery 2013; 23 (2): 134-139. doi: 10.1055/s-0032-1324800
17. Lee DY, Park HJ, Kim BG, Bae DS, Yoon BK et al. Change in the ovarian environment after hysterectomy as assessed by ovarian arterial blood flow indices and serum anti-Mullerian hormone levels. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2010; 151 (1): 82-85. doi: 10.1016/j. ejogrb.2010.02.037
18. Hehenkamp WJ, Volkers NA, Broekmans FJ, de Jong FH, Themmen AP et al. Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy. Human Reproduction 2007; 22 (7): 1996-2005. doi: 10.1093/ humrep/dem105
19. Wang HY, Quan S, Zhang RL, Ye HY, Bi YL et al. Comparison of serum anti-Mullerian hormone levels following hysterectomy and myomectomy for benign gynaecological conditions. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2013; 171 (2): 368-371. doi: 10.1016/j. ejogrb.2013.09.043
20. Atabekoğlu C, Taşkin S, Kahraman K, Gemici A, Taşkin EA et al. The effect of total abdominal hysterectomy on serum antiMullerian hormone levels: a pilot study. Climacteric 2012; 15 (4): 393-397. doi: 10.3109/13697137.2011.642426
21. Visser JA, Durlinger AL, Peters IJ, van den Heuvel ER, Rose UM et al. Increased oocyte degeneration and follicular atresia during the estrous cycle in anti-Mullerian hormone null mice. Endocrinology 2007; 148 (5): 2301-2308. doi: 10.1210/ en.2006-1265
22. Uzumcu M, Kuhn PE, Marano JE, Armenti AE, Passantino L. Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary. The Journal of Endocrinology 2006; 191 (3): 549-558. doi: 10.1677/joe.1.06592
23. Mark-Kappeler CJ, Sen N, Keating AF, Sipes IG, Hoyer PB. Distribution and responsiveness of rat anti-Mullerian hormone during ovarian development and VCD-induced ovotoxicity. Toxicology and Applied Pharmacology 2010; 249 (1): 1-7. doi: 10.1016/j.taap.2010.08.024
24. Baarends WM, Uilenbroek JT, Kramer P, Hoogerbrugge JW, van Leeuwen EC et al. Anti-müllerian hormone and antimüllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology 1995; 136 (11): 4951-4962. doi: 10.1210/ endo.136.11.7588229
25. Souza AZ, Fonseca AM, Izzo VM, Clauzet RM, Salvatore CA. Ovarian histology and function after total abdominal hysterectomy. Obstetrics and Gynecology 1986; 68 (6): 847- 849.
26. Ozdamar S, Ulger H, Sorkun HC, Muderris I. Effects of hysterectomy on ovarian morphology and serum FSH level in rats. Maturitas 2005; 52 (1): 60-64. doi: 10.1016/j. maturitas.2004.12.004
27. Tanaka M, Kumai T, Watanabe M, Matsumoto C, Hirai M et al. Effects of hysterectomy on ovulation and related ovarian functions in regular estrous cycle rats. Life Sciences 1994; 55 (3): 237-243. doi: 10.1016/0024-3205(94)00885-x
28. Pellatt L, Hanna L, Brincat M, Galea R, Brain H et al. Granulosa cell production of anti-Müllerian hormone is increased in polycystic ovaries. Journal of Clinical Endocrinology and Metabolism 2007; 92 (1): 240-245. doi: 10.1210/jc.2006-1582
29. Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications. Human Reproduction Update 2014; 20 (5): 688- 701. doi: 10.1093/humupd/dmu020
30. Tal R, Seifer DB. Ovarian reserve testing: a user’s guide. American Journal of Obstetrics and Gynecology 2017; 217 (2): 129-140. doi: 10.1016/j.ajog.2017.02.027
31. Chan CC, Ng EH, Ho PC. Ovarian changes after abdominal hysterectomy for benign conditions. Journal of the Society for Gynecologic Investigation 2005; 12 (1): 54-57. doi: 10.1016/j. jsgi.2004.07.004
32. Xiangying H, Lili H, Yifu S. The effect of hysterectomy on ovarian blood supply and endocrine function. Climacteric 2006; 9 (4): 283-289. doi: 10.1080/13697130600865774
33. Petri Nahas EA, Pontes A, Nahas-Neto J, Borges VT, Dias R et al. Effect of total abdominal hysterectomy on ovarian blood supply in women of reproductive age. Journal of Ultrasound in Medicine 2005; 24 (2): 169-174. doi: 10.7863/jum.2005.24.2.169
34. Janson PO, Jansson I. The acute effect of hysterectomy on ovarian blood flow. American Journal of Obstetrics and Gynecology 1977; 127 (4): 349-52. doi: 10.1016/0002- 9378(77)90488-4
35. Ahn EH, Bai SW, Song CH, Kim JY, Jeong KA et al. Effect of hysterectomy on conserved ovarian function. Yonsei Medical Journal 2002; 43 (1): 53-58. doi: 10.3349/ymj.2002.43.1.53
36. Chen L, Zhang L, Fang Z, Li C, Yang Y et al. Naoxintong restores collateral blood flow in a murine model of hindlimb ischemia through PPARδ-dependent mechanism. Journal of Ethnopharmacology 2018; 227: 121-130. doi: 10.1016/j. jep.2018.08.032