Stress-associated ovarian damage, infertility, and delay in achieving pregnancy and treatment options.

Daño ovárico, infertilidad y retraso en la concepción relacionados con el estrés y opciones de tratamiento.

• Gulsah Aynaoglu Yildiz Etlik Zubeyde Hanim Maternity and Women’s Health Teaching and Research Hospital, Ankara-Turkey. https://orcid.org/0000-0002-3283-7783
• Omer Erkan Yapca Ataturk University, Erzurum, Turkey. https://orcid.org/0000-0002-5578-0126
• Kemal Dinc Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0003-4955-455X
• Cebrail Gursul Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0001-6521-6169
• Betul Gundogdu Ataturk University, Erzurum, Turkey. https://orcid.org/0000-0002-3786-3286
• Mehmet Aktas Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0003-1931-8353
• Zeynep Suleyman Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0003-0128-7990
• Seval Bulut Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0003-4992-1241
• Halis Suleyman Erzincan Binali Yildirim University, Erzincan, Turkey. https://orcid.org/0000-0002-9239-4099

DOI: https://doi.org/10.54817/IC.v64n4a8

Palabras clave: daño ovárico, sertralina, cerebrolisina, estrés, ratas

Resumen

Muchos tipos de estrés, incluido el estrés psicológico, afectan negativamente a la salud reproductiva. El objetivo de este estudio fue investigar los efectos de la sertralina (un inhibidor selectivo de la recaptación de serotonina), la cerebrolisina (neuroprotector/neurotrófico) y una combinación de ambos contra el daño ovárico, la infertilidad y el retraso del embarazo inducido por el estrés en ratas hembra. Las ratas se dividieron en cinco grupos (n=14/ cada grupo), como sanas (HG), control de estrés (StC), estrés+sertralina (SS), estrés+cerebrolisina (SC) y estrés+sertralina+cerebrolisina (SSC) . Para inducir el estrés, los animales (excepto el HG) se mantuvieron en posición supina con las extremidades anteriores y posteriores (FIM) atadas durante una hora. Luego, se administró sertralina (20 mg/kg) por vía oral al grupo SS. Cerebrolysin (2,5 mL/kg) se inyectó al grupo SC por vía subcutánea. Se administró sertralina+cerebrolisina al grupo SSC con los mismos métodos y dosis. La FIM y la administración de fármacos continuaron durante 30 días. Se sacrificaron seis ratas de cada grupo con anestesia de dosis alta, se extirparon los tejidos de los ovarios derecho e izquierdo y se examinaron bioquímica e histopatológicamente. Las ratas restantes se tomaron para reproducción. La exposición al estrés en ratas provocó un aumento de los niveles de malondialdehído (MDA), factor de necrosis tumoral alfa (TNF-α), interleucina-1β (IL-1β) e interleucina-6 (IL-6) y una disminución del glutatión total (tGSH). El estrés se relacionó con daño histopatológico, infertilidad y retraso en el parto. La combinación de sertralina y cerebrolisina fue la más efectiva para prevenir estos cambios, con sertralina y cerebrolisina solas en segundo y tercer lugar, respectivamente. Los inhibidores selectivos de la recaptación de serotonina (ISRS) y los medicamentos relacionados pueden ser beneficiosos en el tratamiento del daño ovárico relacionado con el estrés, la infertilidad y el retraso en el embarazo.

Citas

Nargund VH. Effects of psychological stress on male fertility. Nat Rev Urol 2015;12:373-382.

Sominsky L, Hodgson DM, McLaughlin EA, Smith R, Wall HM, Spencer SJ. Linking Stress and Infertility: A Novel Role for Ghrelin. Endocr Rev 2017;38:432-467.

Abdel Hafez SMN, Allam F, Elbassuoni E. Sex differences impact the pancreatic response to chronic immobilization stress in rats. Cell Stress Chaperones 2021;26:199- 215.

Mamgain A, Sawyer IL, Timajo DAM, Rizwan MZ, Evans MC, Ancel CM, Inglis MA, Anderson GM. RFamide-related peptide neurons modulate reproductive function and stress responses. J Neurosci 2021;41:474-488.

Damone AL, Joham AE, Loxton D, Earnest A, Teede HJ, Moran LJ. Depression, anxiety and perceived stress in women with and without PCOS: a community-based study. Psychol Med 2019;49:1510-1520.

Lakatos E, Szigeti JF, Ujma PP, Sexty R, Balog P. Anxiety and depression among infertile women: a cross-sectional survey from Hungary. BMC Womens Health 2017;17:48.

Li M, Li C, Yu H, Cai X, Shen X, Sun X, Wang J, Zhang Y, Wang C. Lentivirusmediated interleukin-1β (IL -1β) knockdown in the hippocampus alleviates lipo-polysaccharide (LPS)-induced memory deficits and anxiety and depression-like behaviors in mice. J Neuroinflammation 2017;14:190.

Chukwuebuka NB, Emeka OA, Irukefe OS, Iju WJ, Godsday OU, Temitope OG, Nneamaka EC, Peter AC. Stress-Induced Morphological Changes of Ovarian Histology in Female Wistar Rats. Biomedical & Pharmacology Journal. 2020;13:1625-1643.

Kadioglu B, Gundogdu B, Kurt N, Bilgin AO, Suleyman H, Suleyman Z. The effect of rhodiola rosea root extract on stress induced ovarian damage, infertility and reproductive disorders in female rats. Clinical and Experimental Obstetrics & Gynecology. 2020;47:530-536.

Abdel Salam OM, Mohammed NA, Sleem AA, Farrag AR. The effect of antidepressant drugs on thioacetamide-induced oxidative stress. Eur Rev Med Pharmacol Sci 2013;17:735-744.

Baharav E, Bar M, Taler M, Gil-Ad I, Karp L, Weinberger A, Weizman A. Immunomodulatory effect of sertraline in a rat model of rheumatoid arthritis. Neuroimmunomo-dulation 2012;19:309-318.

Shulyak A, Gorpynchenko I, Drannik G, Poroshina T, Savchenko V, Nurimanov K. The effectiveness of the combination of rectal electrostimulation and an antide pressant in the treatment of chronic abacterial prostatitis. Cent European J Urol 2019;72:66-70.

Hou R, Ye G, Liu Y, Chen X, Pan M, Zhu F, Fu J, Fu T, Liu Q, Gao Z, Baldwin DS, Tang Z. Effects of SSRIs on peripheral in- flammatory cytokines in patients with Generalized Anxiety Disorder. Brain Behav Immun 2019;81:105-110.

El-Marasy SA, El Awdan SA, Hassan A, Ahmed-Farid OA, Ogaly HA. Anti-depressant effect of cerebrolysin in reserpine induced depression in rats: Behavioral, biochemical, molecular and immunohistochemical evidence. Chem Biol Interact 2021;334:109329.

Safarova T, Gavrilova S. The use of neuro protectors in the treatment of late depression. Zhurnal Nevrologii i Psikhiatrii Imeni SS Korsakova 2020;120:46-53.

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-358.

Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192-205.

Cakir B, Kasımay O, Kolgazi M, Ersoy Y, Ercan F, Yegen BC. Stress-induced multiple organ damage in rats is ameliorated by the antioxidant and anxiolytic effects of regular exercise. Cell Biochem Funct 2010;28:469-479.

Islam MT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 2017;39:73-82.

Aynaoglu Yildiz G, Yildiz D, Yapca OE, Suleyman B, Arslan YK, Kurt N, Suleyman H. Effect of diazepam, sertraline and melatonin on the stress-induced reproductive disorders and intrauterine growth restriction in female rats. J Matern Fetal Neonatal Med 2021;34:4103-4109.

Yuceli S, Suleyman B, Yazici GN, Mammadov R, Cankaya M, Kunak CS, Bulut S, Suleyman H, Altuner D. Effect of taxifolin on ischemia/reperfusion-induced oxidative injury of sciatic nerve in rats. Transplant Proc 2021;53:3087-3092.

Gaweł S, Wardas M, Niedworok E, Wardas P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiadomosci lekarskie (Warsaw, Poland: 1960) 2004;57:453-455.

Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009;30:1-12.

Unlubilgin E, Suleyman B, Balci G, Atakan Al R, Cankaya M, Arslan Nayki U, Suleyman H. Prevention of infertility induced by ovarian ischemia reperfusion injury by benidipine in rats: Biochemical, gene expression, histopathological and immunohistochemical evaluation. J Gynecol Obstet Hum Reprod 2017;46:267-273.

Wang XM, Ma ZY, Song N. Inflammatory cytokines IL -6, IL -10, IL -13, TNF-α and peritoneal fluid flora were associated with infertility in patients with endometriosis. Eur Rev Med Pharmacol Sci 2018;22:2513- 2518.

Senashova O, Reddy AP, Cameron JL, Bethea CL. The effect of citalopram on midbrain CRF receptors 1 and 2 in a primate model of stress-induced amenorrhea. Reprod Sc. 2012;19:623-632.

Berent D, Zboralskı K, Macander M. Antioxidant properties of cerebrolysin–an old drug with newly discovered capabilities. The Polish Journal of Aviation Medicine and Psychology. 2014;20:25.

Ince S, Ozer M, Goktug Kadioğlu B, Kuzucu M, Karahan Yilmaz S, Özkaraca M, Gezer A, Suleyman H. The effect of adenosine triphosphate on bevacizumab induced ovarian damage and reproductive dysfunction in rats. Gen Physiol Biophys. 2021;40:71-78.

Ince S, Ozer M, Kadioglu BG, Kuzucu M, Ozkaraca M, Gezer A, Suleyman H, Cetin N. The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats. J Obstet Gynaecol Res. 2021;47:2140-2148.