Histological Sequel Following Exposure to Levonorgestrel on Wistar Rat Ovary
Subject Areas :
Journal of Chemical Health Risks
Efe Ahama
1
,
Igho Emmanuel Odokuma
2
,
Ehizokhale Santos Ehebha
3
,
Oghenesuvwe Princess Enakpoya
4
1 - Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria
2 - Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria
3 - Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria
4 - Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria
Received: 2022-08-07
Accepted : 2023-05-31
Published : 2024-03-01
Keywords:
Ovary,
Histological,
Sequelae,
Levonorgestrel,
Abstract :
The action of sex hormones could be altered through the introduction of exogenous synthetic substances, which have been shown by several studies to possess deleterious sequelae on the ovaries. Reports on the detailed histology following the exposure to Levonorgestrel (L) are scanty and none has espoused the use of progestin-only contraceptives (post-coital pills) on the ovary. The study, therefore, evaluated the histological sequelae following exposure to Levonorgestrel on the Wistar rat ovary. Ethical approval for the study was granted by the Research and Ethics Committee in the Faculty of Basic Medical Sciences of Delta State University, Abraka. Forty Adult female Wistar rats, grouped into A and B were investigated. A, control, consisting of 20 rats, and B, test group, 20 rats. Both groups were further divided into 10 subgroups respectively, with each consisting of 20 rats. Subgrouping was done accordingly into 3rd, 6th, 9th, 12th, 15th 18th, 21st 24th 27th and 30th days respectively. Group A received food and distilled water only while group B rats received 0.025mg kg-1 of (L), food and water. Ovary revealed untoward effects of Levonorgestrel, seen at day 6 to day 30 for routine staining pattern. Also seen is a gradatory staining intensity of brown nuclei for progesterone and estrogen receptors for immunochemical staining pattern. This treatise underscored the deleterious outcomes in female gonads exposed to Levonorgestrel and cytoarchitectural peculiarities in ovaries exposed to either combined or emergency oral contraceptives were well espoused.
References:
Pooja B., Smriti A., 2018. Review Article: Use of Anabolic Steroids among Adults. Int Res J Hum Res Soc Sci. 5(6), 2394 - 4218.
Regidor P.A., 2018 Clinical relevance in present day hormonal contraception. Horm Mol Biol Clin Investig. 37(1), 10.1515/hmbci-2018-0030.
D’Arpe S., Di Feliciantonio M., Candelieri M., Franceschetti S., Piccioni M.G., Bastianelli C., 2016. Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review. Reprod BioMed Online. 33, 436 - 448
Chen S., Dai X., Gao Y., Shen F., Ding J., Chen Q., 2017. The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer. Sci Rep. 7, 16922
Alano A., Hanson L., 2018. Women's perception about contraceptive use benefits towards empowerment. A phenomenological study in Southern Ethiopia. PLos One. 13(9), e0203432.
Shukla A., Jamwal R., Bala J., 2017. Adverse effect of combined oral contraceptive pills. Asian J Pharm Clin Res. 10(1), 17-21.
Wang C., Cao H., 2019. Persisting Regional Disparities in Modern Contraceptive Use and Unmet Need for Contraception among Nigerian Women. Biomed Res Int. 9103928.
Fayehun F., 2017. “Contraceptive use in Nigeria is incredibly low. This could be why”. Online, Accessed from: <https://www.iol.co.za/news/africa/contraceptive-use-in-nigeria-is-incredibly-low-this-could-be-why10502316> 9 June 2019.
Goldstuck N.D., Kluge J., 2017. Fourth Generation Oral Contraception: A new era in safety. Obstet Gynecol Forum. 27(1), 25 - 28.
Batres C., Porcheron A., Kaminski G., Courreges S., Morizot F., Russell R., 2018. Evidence that the hormonal contraceptive pill is associated with cosmetic habits. Front Psychol. 9, 14 - 59.
Bahaa A.A., Khudair Z.W., Mohammed A.A., Majeed S.K., 2015. Toxicological pathology of contraceptive in rat by oral intubation for six months. Adv Life Sci Tech. 32, 2224 - 7181.
Kroll R., Seidman L., Howard B., Ricciotti N., Hsieh J., Weiss H., 2015. A phase 1, multicenter, open-label study to evaluate ovarian follicular activity and hormone levels with an extended regimen combined oral contraceptive with low dose ethinylestradiol supplementation. Eur J Contracept Reprod Health Care. 20, 249 - 258.
Jain R., Mauralidhar S., 2012. Contraceptive methods: Needs, options and utilization. Delhi University, New Delhi, India. J Obstet Gynecol India. 61(6), 626 - 634.
King T.L., Brucker M.C., Kriebs J.M., Fahey J.O., 2013. Varney’s Midwifery, Burlington: Jones and Bartlett Learning. 347 - 348
Jameson J.L., DeGroot L.J., deKretser D.M., Giudice L.C., Grossman A.B., Melmed S., Potts J.T., Weir G.C., Glasier A., 2016. Contraception. In Endocrinology Adult Pediatric; Saunders: Philadelphia, PA, USA. 2297 - 2309.
Schreiber C.A., Barnhart K., 2018. Contraception. In Yen & Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 8th edition. Saunders, W.B., Philadelphia, USA. 962 - 978
Smith-Mccune K., Thomas R., Averbach S., Seidman D., Takeda M., Houshdaran S., Giudice L.C., 2020. Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome, Sci Rep. 10:6888. https://doi.org/10.1038/s41598-020-63798-8
Trussell J., Jordan B., 2006. Mechanism of action of emergency contraceptive pills. Contraception. 74, 87 - 9.
Croxatto H.B., Devoto L., Durand M.E., Larrea F., Nagle C., Ortiz M.E., Vanuman D., Vega M., von Heltzen K., 2001. Mechanism of action of hormonal p used for emergency contraception: A review of the literature. Contraception. 63, 111 -121
Abeer M.H., Magda M.N., Somaya H.M., Fouad M.B., 2006. Effect of Monthly Injectable Contraceptive (Mesigyna) on the Uterus of Adult Female Albino Rat: Histological and Immunohistochemical Study. Egypt J Hosp Med. 22, 80 - 97.
Meresman G.F., Auge L., Baranao R.I., Lombardi E., Tesone M., Sueldo C., 2002. Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril. 77, 1141 - 1147.
Horinzy C., 2019. Acclimating research animal through effective nurturing. Taconic: Model for life. https://tconic.com/taconic-insights/
Bailoo et al., 2018. Effects of cage enrichment on behaviour, welfare and outcome variability in female mice. Front Behav Neurosci. 12, 232.
Festing M.F.W., 2020. How to Reduce the Number of Animals Used in Research by Improving Experimental Design and Statistics, ANZCCART Human Science Fact Sheet T10.
Kim S., Shin S., Yoo Y., Kim N., Kim D., Zhang D., Park J., Yi H., Kim J. 2015. Shin H. Oral toxicity of isotretinoin, misoprostol, methotrexate, mifepristone and levonorgestrel as pregnancy category X medications in female mice. Exp Ther Med. 9, 853 - 859
Adigun M.S., Fasogbon S.A., Ajileye A.B., Arije B.S., 2016. Histo-toxic effect of the drug postinor-2 on the liver of female Wistar rat. European J Biomed Pharm Sci. 3(12), 528 - 530.
Yuanyuan C., Xiaobo S., 2016. Repeated use of mifepristone and levonorgestrel and their effect on the ovarian function in mice J Obstet Gynaecol Res. 42, 11
Christina V., Tushar B., 2020. Levonorgestrel. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK539737/?report=printable
Black K.I., Hussainy S.Y., 2017. Emergency contraception: Oral and intrauterine options. Aust Fam Physician. 46(10), 722 - 726.
Oyem J.C., Chris-Ozoko L.E., Enaohwo M.T., Otabor F.O., Okudayo V.A., Udi O.A., 2021. Antioxidative properties of Ocimum gratissimumalters Lead acetate induced oxidative damage in lymphoid tissues and hematological parameters of adult Wistar rats. Toxicol Rep. 8, 215 - 222
Ahama E.E., Odokuma E. I. 2023. Histomorphological Effects of Oral Nicotine administration on the testes of adult wistar rats. J. Chem. Heal. Ris. 13(2): 291 - 298
Rieger J., Pelckmann L.M., Drewes B., 2021. Preservation and Processing of Intestinal Tissue for the Assessment of Histopathology. Methods Mol Biol. 2223, 267 - 280
Garg S., Marwah N., Chauhan G., Gupta S., Goyal, R., Dahiya, P., Jain, P. Sen, P. 2014. Estrogen and progesterone receptor expression and its Correlation with various Clinicopathological parameter in ovarian tumors. Middle East J Cancer. 5(2), 97 - 103
Tighe C., 2018. Hundreds of patients are claiming the mirena IUD causes a neurological disorder-but experts say more research is needed”. Accessed 6 May 2019 (Rewire News), from: https://rewire.news/article/2018/12/04/hundreds of patients are claiming the mirena iud causes aneurological disorder but experts say more research is needed.
Kristen P.W., Julia V.J., 2008. Evaluation of extended and continuous use oral contraceptives, Ther Clin Risk Manag. 4(5), 905 - 911
Meng C.X., Marions L., Bystrom B., Gemzell-Danielson K., 2010. Effects of oral and vaginal administration of levonorgestrel emergency contraception on markers of endometrial receptivity. Hum Reprod. 25(4), 874 - 883.
Simeon R.M., 2012. Pharmacodynamics for the prescribers, Clinical Pharmacology, Elsevier Ltd. pp. 351 - 356
Massawe A.W., Makundi R.H., Zhang Z., Mhamphi G., Liu M., Li H., Belmain S.R., 2018. Effect of synthetic hormones on reproduction in Mastomys natalensis. J Pest Sci. 91(1), 157 - 168
Christie M.J., 2008. Cellular neuro-adaptations to chronic opioids: tolerance, withdrawal and addiction. Br J Pharmacol. 154, 384 - 396
Urzua U., Chacon C., Espinoza R., Martínez S., Hernandez N., 2018. Parity-Dependent Hemosiderin and Lipofuscin Accumulation in the Reproductively Aged Mouse Ovary. Analytical Cellular Pathology. https://doi.org/10.1155/2018/1289103
Orbo A., 2010. Down-regulated progesterone receptor A and B coinciding with successful treatment of endometrial hyperplasia by the levonorgestrel impregnated intrauterine system. Acta Obstet Gynecol Scand. 89(11), 1438 - 1446.
Munzel T., Daiber A., Gori T., 2011. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. 123, 2132 - 2144.
de Medeiros S.F., 2017. Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome. Reprod Biol Endocrinol. 15(1), 93.
Lindgren P.R., Cajander S., Backstrom T., Gustafsson J., Makela S., Olofsson J.I., 2004. Estrogen and progesterone receptors in ovarian epithelial tumors. Mol Cell Endocrinol. 221, 97 - 104
Sayed N., Kim D.D., Fioramonti X., Iwahashi T., Duran W.N., Beuve A., 2008. Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance. Circ Res. 103, 606 - 614.
Dinh A., Sriprasert I., Williams A.R., Archer D.F., 2015. A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women. Contraception. 91, 360 - 367
Lv X., Shi D., 2011. The Effects of quinestrol as a contraceptive in Mongolian Gerbils (Meriones unguiculatus). Exp Anim. 60(5), 489 - 496.
Chen S., Dai X., Gao Y., Shen F., Ding J., Chen Q., 2017. The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer. Sci Rep. 7, 16922
Eidne K.A., 2003. Heptahelical Receptor Superfamily, Encyclopedia of Hormones, Academic Press. Copyright 2003, Elsevier Science (USA). pp. 241 - 255.
Whiting K.P., Restall C.J., Brain P.F., 2000 Steroid hormone-induced effects on membrane uidity and their potential roles in non-genomic mechanisms. Life Sci. 67, 743 - 757
Naik P.S., 2015. Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study. J Midlife Health. 6, 178 - 183
Goodman L.S., Brunton L.L., Chabner B., Knollmann B.C., 2011. Goodman and Gilman’s pharmacological basis of therapeutics. New York, McGraw-Hill, 12th Edition. Chapter 3. pp. 42 - 71
Kuhn-Velten W.N., Kempfle M.A., 1993. Biochim Biophys Acta. 1145, 185 - 190.
Maqueo M., Rice-Wray E., Calderon J.J., Goldzieher J.W., 1972. Ovarian morphology, after prolonged use of steroid contraceptives. Contraception. 5, 177 - 185
Ohvo-Rekila H., Ramstedt B., Leppimaki P., Slotte J.P., 2002. Cholesterol interactions with phospholipids in membranes. Prog Lipid Res. 41, 66 - 97.
Noguchi T., Kitawaki J., Tamura T., Kim T., Kanno H., Yamamoto T., Okada H., 1993. Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women. J Steroid Biochem Mol Bio. 44(4-6), 657 - 660.
Rodriguez C., Patel A.V., Calle E.E., Jacob E.J., Thun M.J., 2001. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA. 285, 1460 - 1465.
Grundy H.F., 1991. Lecture Notes on Pharmacology. Blackwell Scientific Publications, Carlton, Victoria, Australia (Pty Ltd), 2nd edition. 2, 90 - 94
von Hertzen H., Piaggio G., Ding J., Chen J., Song S., Bártfai G., Ng E., Gemzell Danielson K., Oyunbileg A., Wu S., Cheng W., Ludicke F., Pretnar-Darovec A., Kirkman R., Mittal S., Khomassuridze A., Apter D., Peregoudov A., 2002. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial, Lancet. 360, 1803 - 10
Dupuis C.S., Kim Y.H., 2015. Ultrasonography of adnexal causes of acute pelvic pain in pre-menopausal non-pregnant women. Ultrasonography (Seoul, Korea). 34(4), 258 - 67.
Nusblast A.D., Bright L.J., Turkewitz A.P., 2012. Conservation and innovation in Tetrahymena Membrane Traffic: Proteins Lipids and Compartments. Methods Cell Bio. 109(6), 141 - 175.