Effects of Metformin in High Concentrations on the Fertility of Female Sailfin Molly Poecilia latipinna

Authors

  • Abdul-Ameer M.F. Al-Hachamei Department of Fisheries and Marine Resources, College of Agriculture, the University of Basrah, Iraq.
  • Hussein A. Saud Department of Pathological Analyses, College of Sciences, University of Basrah, Iraq.
  • Sajed S. H. Alnoor Department of Pathological Analyses, College of Sciences, University of Basrah, Iraq.

DOI:

https://doi.org/10.54174/hfpbwr68

Keywords:

FSH, LH, metformin, Poecilia latipinna

Abstract

Metformin is a medicine that is used to treat type 2 diabetes and polycystic ovary syndrome (PCOS). This study investigated the effects of exposing the sailfin molly fish to sub-lethal concentrations of 0.008 mol.L-1 of metformin. The results showed that metformin caused disturbances in the endocrine glands, especially the pituitary hormones (GTHs). Metformin increased the expression of the Fshb and inhibited the Lhb genes in the pituitary gland, which led to higher levels of FSH and lower levels of LH hormones in the blood of fish. These hormonal changes led to irregularities in the ovarian development of female fish, such as an increase in the first stage of primary eggs and a delay in the final stage of embryo production.

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References

Adhish, M., & Manjubala, I. (2023). Effectiveness of zebrafish models in understanding human diseases—A review of models. Heliyon.‏ https://doi.org/10.1016/j.heliyon.2023.e14557

Agius, L., Ford, B. E., & Chachra, S. S. (2020). The metformin mechanism on gluconeogenesis and AMPK activation: the metabolite perspective. International journal of molecular sciences, 21(9), 3240. https://doi.org/10.3390/ijms21093240

Ambrosio-Albuquerque, E. P., Cusioli, L. F., Bergamasco, R., Gigliolli, A. A. S., Lupepsa, L., Paupitz, B. R., Barbieri, P.A., Borin-Carvalho, L.A., & de Brito Portela-Castro, A. L. (2021). Metformin environmental exposure: A systematic review. Environmental Toxicology and Pharmacology, 83, 103588.‏ https://doi.org/10.1016/j.etap.2021.103588

Aungst .Christina, (2022). What Is Metformin Used for, and How Does It Work Exactly? https://www.goodrx.com/metformin/metformin-how-does-it-work-what-does-it-do

Bahamonde, P. A., Munkittrick, K. R., & Martyniuk, C. J. (2013). Intersex in teleost fish: are we distinguishing endocrine disruption from natural phenomena?. General and comparative endocrinology, 192(1), 25-35.‏ http://dx.doi.org/10.1016/j.ygcen.2013.04.005

Bai, B., & Chen, H. (2021). Metformin: A novel weapon against inflammation. Frontiers in pharmacology, 12, 622262.‏ https://doi.org/10.3389/fphar.2021.622262

Bailey, C. J. (2017). Metformin: historical overview. Diabetologia, 60(9), 1566-1576.‏ https://doi.org/10.1007/s00125-017-4318-z

Bailone, R. L., Fukushima, H. C. S., Ventura Fernandes, B. H., De Aguiar, L. K., Corrêa, T., Janke, H., Setti,P.G., Roça, R. De O. & Borra, R. C. (2020). Zebrafish as an alternative animal model in human and animal vaccination research. Laboratory animal research, 36, 1-10.‏ https://doi.org/10.1186/s42826-020-00042-4

Barros, S., Alves, N., Pinheiro, M., Ribeiro, M., Morais, H., Montes, R., Rodil, R., Quintana, J.B., Coimbra, A. M., Santos, M. M., & Neuparth, T. (2022a). Are fish populations at risk? Metformin disrupts zebrafish development and reproductive processes at chronic environmentally relevant concentrations. Environmental Science & Technology, 57(2), 1049-1059 https://doi.org/10.1021/acs.est.2c05719

Barros, S., Ribeiro, M., Coimbra, A. M., Pinheiro, M., Morais, H., Alves, N., Montes, R ., Rodil, R., Quintana, J. B., Santos ,M. M., & Neuparth, T. (2022b). Metformin disrupts Danio rerio metabolism at environmentally relevant concentrations: A full life-cycle study. Science of The Total Environment, 846, 157361. https://doi.org/10.1016/j.scitotenv.2022.157361

Biran, J., & Levavi-Sivan, B. (2018). Endocrine Control of Reproduction Fish. Pp. 362–368. In Skinner, M. K. (Ed.). Encyclopedia of Reproduction. Vol. 6, 2nd ed. Academic Press: Elsevier. http://dx.doi.org/10.1016/B978-0-12-809633-8.20579-7

Blanco, A. M. (2020). Hypothalamic-and pituitary-derived growth and reproductive hormones and the control of energy balance in fish. General and Comparative Endocrinology, 287, 113322.‏ https://doi.org/10.1016/j.ygcen.2019.113322

Cabrita, E., Robles, V., & Herráez, P. (Eds.). (2008). Methods in reproductive aquaculture: marine and freshwater species. CRC press.‏p.p(34-37) https://books.google.iq/books?hl=ar&lr=&id=e5NcUsHvTOwC&oi=fnd&pg=PP1&dq=.+Methods+in+reproductive+aquaculture:+marine+and+freshwater+species&ots=AWQpexKIuK&sig=WMpzFJt5diOfDdTqQN8NWLVJgVk&redir_esc=y#v=onepage&q=.%20Methods%20in%20reproductive%20aquaculture%3A%20marine%20and%20freshwater%20species&f=false

Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy, K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Research Reviews, 40, 31-44.‏ https://doi.org/10.1016/j.arr.2017.08.003

Chen, X., Liu, B., & Lin, D. (2022). Sexual Maturation, Reproductive Habits, and Fecundity of Fish. Biology of Fishery Resources, 113-142.‏ https://doi.org/10.1007/978-981-16-6948-4_5

Cheng, F. F., Liu, Y. L., Du, J., & Lin, J. T. (2022). Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease. Aging and Disease, 13(4), 970-986.‏ https://doi.org/10.14336/ad.2021.1213

Choi, T. Y., Choi, T. I., Lee, Y. R., Choe, S. K., & Kim, C. H. (2021). Zebrafish as an animal model for biomedical research. Experimental & Molecular Medicine, 53(3), 310-317.‏ https://doi.org/10.1038/s12276-021-00571-5

Costa, G. C., & Schlupp, I. (2020). Placing the hybrid origin of the asexual Amazon molly (Poecilia formosa) based on historical climate data. Biological Journal of the Linnean Society, 129(4), 835-843.‏ https://doi.org/10.1093/biolinnean/blaa010

da Trindade, M. T., Kogawa, A. C., & Salgado, H. R. N. (2018). Metformin: a review of characteristics, properties, analytical methods and impact in the green chemistry. Critical reviews in analytical chemistry, 48(1), 66-72. https://doi.org/10.1080/10408347.2017.1374165

Davies, S. (2022). Metformin use and vitamin B12 deficiency: New MHRA guidance. Journal of Diabetes Nursing, 26(5).‏ 259. https://diabetesonthenet.com/journal-diabetes-nursing/metformin-vitamin-b12-deficiency-mhra/

Dewi, R. R., Siallagan, W., & Suryanto, D. (2018). The efficacy of sodium chloride application in the control of fish lice (Argulus sp.) infection on tilapia (Oreochromis niloticus). Acta Aquatica: Aquatic Sciences Journal, 5(1), 4-7. https://doi.org/10.1016/B978-0-12-809633-8.20624-9

Drugs.com (2022), Metformin Side Effects, https://www.drugs.com/sfx/metformin-side-effects.html

Elizalde-Velázquez, G. A., & Gómez-Oliván, L. M. (2020). Occurrence, toxic effects and removal of metformin in the aquatic environments in the world: Recent trends and perspectives. Science of The Total Environment, 702, 134924. https://doi.org/10.1016/j.scitotenv.2019.134924

Faure, M., Bertoldo, M. J., Khoueiry, R., Bongrani, A., Brion, F., Giulivi, C., Dupont, J., & Froment, P. (2018). Metformin in Reproductive Biology. Frontiers in Endocrinology, 9, 393399. https://doi.org/10.3389/fendo.2018.00675

Florida Museum of Natural History, (2023). Poecilia latipinna, DISCOVER FISHES, Available https://www.floridamuseum.ufl.edu/discover-fish/species-profiles/poecilia-latipinna/

Fontaine, E. (2018). Metformin-Induced Mitochondrial Complex I Inhibition: Facts, Uncertainties, and Consequences. Frontiers in Endocrinology, 9, 390473. https://doi.org/10.3389/fendo.2018.00753

Foretz, M., Guigas, B., & Viollet, B. (2019). Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nature Reviews Endocrinology, 15(10), 569-589. https://doi.org/10.1038/s41574-019-0242-2

Genazzani, A. D., Ricchieri, F., & Lanzoni, C. (2010). Use of Metformin in the Treatment of Polycystic Ovary Syndrome. Women’s Health. 6(4), 577–593. https://doi.org/10.2217/WHE.10.43

Gershman, J. (2022). What to Know About Taking Vitamin B12 and Metformin, https://www.goodrx.com/metformin/metformin-and-vitamin-b12

Gonzalez, R., Cooper, J., & Head, D. (2005). Physiological responses to hyper-saline waters in sailfin mollies (Poecilia latipinna). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 142(4), 397-403. https://doi.org/10.1016/j.cbpa.2005.08.008

Guzmán, J. M., Luckenbach, J. A., Yamamoto, Y., & Swanson, P. (2014). Expression profiles of Fsh-regulated ovarian genes during oogenesis in coho salmon. PloS one, 9(12), e114176.‏ https://doi.org/10.1371/journal.pone.0114176

Hashim, H. A. (2016). Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?. Reproductive biomedicine online, 32(1), 44-53.‏ https://doi.org/10.1016/j.rbmo.2015.09.015

Hassler, M. R., Redl, E., Hudson, Q. J., Miller, W. J., & Egger, G. (2016). Basic Epigenetic Mechanisms and Phenomena. Drug Discovery in Cancer Epigenetics, 3-40. https://doi.org/10.1016/B978-0-12-802208-5.00001-1

Hatef, A., & Unniappan, S. (2019). Metabolic hormones and the regulation of spermatogenesis in fishes. Theriogenology, 134, 121-128. https://doi.org/10.1016/j.theriogenology.2019.05.021

Herzig, S., & Shaw, R. J. (2018). AMPK: Guardian of metabolism and mitochondrial homeostasis. Nature Reviews Molecular Cell Biology, 19(2), 121-135. https://doi.org/10.1038/nrm.2017.95

Hollander-Cohen, L., Golan, M., & Levavi-Sivan, B. (2021). Differential regulation of gonadotropins as revealed by transcriptomes of distinct LH and FSH cells of fish pituitary. International Journal of Molecular Sciences, 22(12), 6478.‏ https://doi.org/10.3390/ijms22126478

Huhtala, M. S., Tertti, K., & Rönnemaa, T. (2020). Serum lipids and their association with birth weight in metformin and insulin treated patients with gestational diabetes. diabetes research and clinical practice, 170, 108456 https://doi.org/10.1016/j.diabres.2020.108456

Jiang, S., Tang, T., Sheng, Y., Li, R., & Xu, H. (2022). The Effects of Letrozole and Metformin Combined with Targeted Nursing Care on Ovarian Function, LH, and FSH in Infertile Patients with Polycystic Ovary Syndrome. Journal of Healthcare Engineering, 2022.‏ https://doi.org/10.1155/2022/3712166

Kumar, P., Behera, P., Christina, L., & Kailasam, M. (2021). Sex Hormones and Their Role in Gonad Development and Reproductive Cycle of Fishes. Recent updates in molecular Endocrinology and Reproductive Physiology of Fish: An Imperative step in Aquaculture, 1-22.‏ https://doi.org/10.1007/978-981-15-8369-8_1

Lacouture, A., Lafront, C., Peillex, C., Pelletier, M., & Audet-Walsh, É. (2022). Impacts of endocrine-disrupting chemicals on prostate function and cancer. Environmental Research, 204, 112085.‏ https://doi.org/10.1016/j.envres.2021.112085

Lamming, D. W., Ye, L., Sabatini, D. M., & Baur, J. A. (2013). Rapalogs and mTOR inhibitors as anti-aging therapeutics. The Journal of clinical investigation, 123(3), 980-989.‏ https://doi.org/10.1172/jci64099

Lashen, H. (2010). Role of metformin in the management of polycystic ovary syndrome. Therapeutic advances in endocrinology and metabolism, 1(3), 117-128.‏ https://doi.org/10.1177/2042018810380215

Lauretta, R., Sansone, A., Sansone, M., Romanelli, F., & Appetecchia, M. (2019). Endocrine disrupting chemicals: effects on endocrine glands. Frontiers in endocrinology, 10, 178.‏ | https://doi.org/10.3389/fendo.2019.00178

Lawler, M., (2023). The Possible Benefits of Metformin for Type 2 Diabetes and Other Health Conditions, https://www.everydayhealth.com/type-2-diabetes/metformin-health-benefits-why-they-likely-go-beyond-type-2-diabetes

Lee, J. W., Shin, Y. J., Kim, H., Kim, H., Kim, J., Min, S. A., ... & Park, K. (2019). Metformin-induced endocrine disruption and oxidative stress of Oryzias latipes on two-generational condition. Journal of hazardous materials, 367, 171-181.‏ https://doi.org/10.1016/j.jhazmat.2018.12.084

Lin, W., Yan, Y., Ping, S., Li, P., Li, D., Hu, J., Liu, W., Wen, X., & Ren, Y. (2020). Metformin-induced epigenetic toxicity in zebrafish: experimental and molecular dynamics simulation studies. Environmental science & technology, 55(3), 1672-1681. https://doi.org/10.1021/acs.est.0c06052

Liu, Q., Tong, D., Liu, G., Gao, J., Wang, L. A., Xu, J., Yang, X., Xie, Q., Huang, Y., Pang, J., Wang, L., He, Yong., Zhang, D., Ma, Q., Lan, W., & Jiang, J. (2018). Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration Metformin Inhibits Inflammatory Infiltration in Prostate Cancer. Clinical Cancer Research, 24(22), 5622-5634.‏ https://doi.org/10.1158/1078-0432.CCR-18-0420

Lubzens, E., Young, G., Bobe, J., & Cerdà, J. (2010). Oogenesis in teleosts: how fish eggs are formed. General and comparative endocrinology, 165(3), 367-389. https://doi.org/10.1016/j.ygcen.2009.05.022

Ma, T., Tian, X., Zhang, B., Li, M., Wang, Y., Yang, C., , Wu, J., Wei, X., Qu, Q., Yu, Y., Long, S., Feng, J. W., Li, C., Zhang, C., Xie, C., Wu, Y. Xu, Z., Chen, J., He, Y., Yu, Y., Huang, X., Yao, L., Zhang, L., Zhu, M., & Lin, S. C. (2022). Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature, 603(7899), 159-165. https://doi.org/10.1038/s41586-022-04431-8‏

MacLaren, R. D., Wisniewski, K., & MacLaren, C. (2018). Environmental concentrations of metformin exposure affect aggressive behavior in the Siamese fighting fish, Betta splendens. PLoS One, 13(5), e019725 https://doi.org/10.1371/journal.pone.0197259

Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X. M., Braddock, D. T., Albright, R. A., Prigaro,B.J., . Wood, J. L, Bhanot, S. , . MacDonald, M. J., Jurczak, Mi. J., Camporez, J.P., Lee, H.Yo., Cline, G. W., Samuel, V. T., Kibbey, R.G., Shulman, G. I., Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.M., . Albright, R. A.Braddock, D. T., Prigaro, B. J., Wood, J. L., Bhanot, S., MacDonald, M. J., Jurczak, M. J., Camporez, J.P., Lee, H. Y., . Cline, G. W., Samuel, V. T., Kibbey, R. G.& Shulman, G. I. (2014). Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature, 510(7506), 542-546, https://doi.org/10.1038/nature13270

Mitrašinović-Brulić, M., Buljan, M., & Suljević, D. (2021). Association of LH/FSH ratio with menstrual cycle regularity and clinical features of patients with polycystic ovary syndrome. Middle East Fertility Society Journal, 26(1), 40.‏ https://doi.org/10.1186/s43043-021-00085-0

Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology, 38(1), 23-38.‏ https://doi.org/10.1038/npp.2012.112

Muchlisin, Z. A. (2014). A general overview on some aspects of fish reproduction. Aceh International Journal of Science and Technology, 3(1), 43-52.‏.‏ https://doi.org/10.13170/aijst.3.1.1355

Mudumbi, J. B. N., Ntwampe, S. K. O., Mekuto, L., Matsha, T., & Itoba-Tombo, E. F. (2018). The role of pollutants in type 2 diabetes mellitus (T2DM) and their prospective impact on phytomedicinal treatment strategies. Environmental monitoring and assessment, 190, 1-23.‏ https://doi.org/10.1007/s10661-018-6634-2

Murugan, A. K. (2019). mTOR: Role in cancer, metastasis and drug resistance. In Seminars in cancer biology Vol. 59, pp. 92-111). Academic Press.‏ https://doi.org/10.1016/j.semcancer.2019.07.003

Niemuth, N. J., & Klaper, R. D. (2015). Emerging wastewater contaminant metformin causes intersex and reduced fecundity in fish. Chemosphere, 135, 38-45.‏ https://doi.org/10.1016/j.chemosphere.2015.03.060

Niemuth, N. J., Jordan, R., Crago, J., Blanksma, C., Johnson, R., & Klaper, R. D. (2015). Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish. Environmental toxicology and chemistry, 34(2), 291-296. https://doi.org/10.1002/etc.2793

Phillips, J., Akemann, C., Shields, J. N., Wu, C. C., Meyer, D. N., Baker, B. B., Pitts, D., & Baker, T. R. (2021). Developmental phenotypic and transcriptomic effects of exposure to nanomolar levels of metformin in zebrafish. Environmental toxicology and pharmacology, 87, 103716.‏ https://doi.org/10.1016/j.etap.2021.103716

Planas, D., Pagliuzza, A., Ponte, R., Fert, A., Marchand, L. R., Massanella, M., Gosselin, A., Mehraj,V., Dupuy, F. P., Isnard, S., Goulet, J., Lesage, S., Cohen, E. E. A., Ghali, M. P., Angel, J. B., Chomont, N., Routy, J. P., & Ancuta, P. (2021). LILAC pilot study: effects of metformin on mTOR activation and HIV reservoir persistence during antiretroviral therapy. EBioMedicine, 65, 103270. https://doi.org/10.1016/j.ebiom.2021.103270

Ramos-Júdez, S., Giménez, I., Gumbau-Pous, J., Arnold-Cruañes, L. S., Estévez, A., & Duncan, N. (2022). Recombinant Fish and Lh therapy for spawning induction of previtellogenic and early spermatogenic arrested teleost, the flathead grey mullet (Mugil cephalus). Scientific Reports, 12(1), 6563.‏ https://doi.org/10.1038/s41598-022-10371-0

Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577-1585.‏ https://doi.org/10.1007/s00125-017-4342-z

Rizzo, E., & Bazzoli, N. (2020). Reproduction and embryogenesis. In Biology and physiology of freshwater neotropical fish (pp. 287-313). Academic Press. https://doi.org/10.1016/B978-0-12-815872-2.00013-0

Saadia, Z. (2020). Follicle stimulating hormone (LH: FSH) ratio in polycystic ovary syndrome (PCOS)-obese vs. Non-obese women. Medical Archives, 74(4), 289.‏ https://doi.org/10.5455/medarh.2020.74.289-293

Schaeck, M., Van den Broeck, W., Hermans, K., & Decostere, A. (2013). Fish as research tools: alternatives to in vivo experiments. Alternatives to Laboratory Animals, 41(3), 219-229.‏ https://doi.org/10.1177/026119291304100305

Schaffer, R. (2017). Beyond diabetes, metformin may prove to be a ‘wonder drug, endocrinology. https://www.healio.com/news/ /20170207/beyond-diabetes-metformin-may-prove-to-be-a-wonder-drug,

Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative CT method. Nature protocols, 3(6), 1101-1108. https://doi.org/10.1038/nprot.2008.73

Shakoori, A. R. (2017). Fluorescence in situ hybridization (FISH) and its applications. Chromosome Structure and Aberrations, 343-367.‏ https://doi.org/10.1007/978-81-322-3673-3_16

Shmerling, R. H., (2021). Is metformin a wonder drug? - Harvard Health. https://www.health.harvard.edu/blog/is-metformin-a-wonder-drug-202109222605

Shpakov, A. O. (2021). Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms. Pharmaceuticals, 14(1), 42. https://doi.org/10.3390/ph14010042

Tseng, C. H. (2022). The effect of metformin on male reproductive function and prostate: An updated review. The World Journal of Men's Health, 40(1), 11. https://doi.org/10.5534/wjmh.210001

Tso, L. O., Costello, M. F., Albuquerque, L. E. T., Andriolo, R. B., & Macedo, C. R. (2020). Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, (12).‏ https://doi.org/10.1002/14651858.CD006105.pub4

Vial, G., Detaille, D., & Guigas, B. (2019). Role of mitochondria in the mechanism (s) of action of metformin. Frontiers in endocrinology, 10, 294. https://doi.org/10.3389/fendo.2019.00294

Volkoff, H., & London, S. (2018). Nutrition and reproduction in fish. Pp, 743-748. In Encyclopedia of reproduction. Volume 6, 2nd ed. https://doi.org/10.1016/B978-0-12-809633-8.20624-9

Wang, Y., An, H., Liu, T., Qin, C., Sesaki, H., Guo, S., Radovick, S., Hussain, M., Maheshwari, A., Wondisford, F.E., Rourke, B. O., & He, L. (2019). Metformin improves mitochondrial respiratory activity through activation of AMPK. Cell reports, 29(6), 1511-1523. ‏ https://doi.org/10.1016/j.celrep.2019.09.070

Bridges, H. R., Jones, A. J., Pollak, M. N., & Hirst, J. (2014). Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochemical Journal, 462(3), 475-487.‏

Weichhart, T. (2018). mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology, 64(2), 127-134.‏ https://doi.org/10.1159/000484629

Wu, H., Huang, D., Zhou, H., Sima, X., Wu, Z., Sun, Y., Wu, Z., Wu, Z., Sun, Y., Wang, L., Ruan, Y., Wu, Q., Wu, F., She, T., Chu, Y., Huang, Q., Ning, Z., & Zhang, H. (2022). Metformin: A promising drug for human cancers. Oncology Letters, 24(1), 1-9 https://doi.org/10.3892/ol.2022.13325

Yang, W. K., Hseu, J. R., Tang, C. H., Chung, M. J., Wu, S. M., & Lee, T. H. (2009). Na+/K+-ATPase expression in gills of the euryhaline sailfin molly, Poecilia latipinna, is altered in response to salinity challenge. Journal of Experimental Marine Biology and Ecology, 375(1-2), 41-50. https://doi.org/10.1016/j.jembe.2009.05.004

Ye, J., Luo, D., Xu, X., Sun, M., Su, X., Tian, Z., Zhang, M., & Guan, Q. (2019). Metformin improves fertility in obese males by alleviating oxidative stress-induced blood-testis barrier damage. Oxidative medicine and cellular longevity, 2019. Article ID 9151067. https://doi.org/10.1155/2019/9151067

Yerevanian, A., & Soukas, A. A. (2019). Metformin: mechanisms in human obesity and weight loss. Current obesity reports, 8, 156-164.‏ https://doi.org/10.1007/s13679-019-00335-3

Yilmaz, B., Terekeci, H., Sandal, S., & Kelestimur, F. (2020). Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention. Reviews in endocrine and metabolic disorders, 21, 127-147.‏ https://doi.org/10.1007/s11154-019-09521-z

Zhang, Z., Zhu, B., & Ge, W. (2015). Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN-mediated gene disruption. Molecular Endocrinology, 29(1), 76-98. https://doi.org/10.1210/me.2014-1256

Zohar, Y. (2021). Fish reproductive biology–Reflecting on five decades of fundamental and translational research. General and Comparative Endocrinology, 300, 113544.‏ https://doi.org/10.1016/j.ygcen.2020.113544.

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2024-06-01

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Effects of Metformin in High Concentrations on the Fertility of Female Sailfin Molly Poecilia latipinna. (2024). University of Thi-Qar Journal of Agricultural Research, 13(1), 272-290. https://doi.org/10.54174/hfpbwr68