Sains Malaysiana 53(5)(2024): 1219-1234

http://doi.org/10.17576/jsm-2024-5305-18

 

Effect of Edible Bird Nest Supplementation against Busulfan-Induced Oligospermia in Adult Rats

(Kesan Suplemen Sarang Burung Walit terhadap Oligospermia Teraruh Busulfan pada Tikus Dewasa)

NURUL ATIQAH AZHAR1, KHAIRUL OSMAN2, FARAH HANAN FATHIHAH JAFFAR1, CHUA KIEN HUI1, MOHD FARISYAM MAT ROS1, AINI FARZANA ZULKEFLI1 & SITI FATIMAH IBRAHIM1,*

 

1Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000

Cheras, Kuala Lumpur, Malaysia

2Center for Diagnostics, Therapeutics & Investigations (CODTIS), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

 

Diserahkan: 8 Ogos 2023/Diterima: 29 Mac 2024

 

 

Abstract

WHO estimates that between 48 million couples and 186 million individuals are facing infertility globally. Male infertility contributes to one-third of the problem with oligospermia as a primary underlying cause. Edible bird nest (EBN), a nutritional natural product, has the potential to improve male fertility status. However, the scientific evidence on oligospermia is sparse. Therefore, this study aimed to evaluate the effectiveness of EBN supplementation in busulfan-induced oligospermia of adult rats. Thirty-six eight-week-old Sprague Dawley male rats (N=36) were randomly and equally divided into six groups (n=6): Control, Sham, Busulfan, EBN 250, 500, and 1000 mg/kg/daily. A single dose of 10 mg/kg busulfan was injected intraperitoneally to induce oligospermia. Daily EBN supplementation was administered for 28 consecutive days, started one day following the busulfan injection. Findings showed that sperm concentration, spermatogenesis index scoring, seminiferous tubule diameter, and germ cell height were reduced in busulfan-induced oligospermia. Meanwhile, the apoptosis status was significantly increased. EBN supplementation had significantly increased sperm concentration, spermatogenesis index scoring, germ cell height, and gene expression of p38 and MAPK14. EBN supplementation also reduced apoptosis in the oligospermia group in a dose-dependent manner. In conclusion, daily EBN supplementation has a protective effect in busulfan-induced oligospermia by increasing sperm production, preserving histological features of the testes, reducing apoptosis, and improving gene expression of p38 and MAPK14.

 

Keywords: Edible bird nest; oligospermia; p38; spermatogenesis; sperm concentration

 

 

Abstrak

WHO menganggarkan bahawa antara 48 juta pasangan dan 186 juta individu menghadapi ketidaksuburan di seluruh dunia. Kemandulan lelaki menyumbang kepada satu pertiga daripada masalah ketidaksuburan tersebut dengan oligospermia merupakan punca utama. Sarang burung walit (EBN), produk semula jadi yang mengandungi banyak khasiat, berpotensi untuk meningkatkan status kesuburan lelaki. Walau bagaimanapun, bukti saintifik mengenai oligospermia masih kurang. Oleh itu, kajian ini bertujuan untuk menilai keberkesanan suplementasi EBN terhadap oligospermia teraruh busulfan dalam tikus dewasa. Tiga puluh enam ekor tikus jantan Sprague Dawley (N=36) berumur lapan minggu dibahagikan secara rawak kepada enam kumpulan (n=6): Kawalan, Sham, Busulfan, EBN 250, 500 dan 1000 mg/kg/hari. Suntikan tunggal 10 mg/kg busulfan dilakukan secara intraperitoneal untuk mengaruh oligospermia. Suplementasi EBN diberikan selama 28 hari berturut-turut, bermula sehari selepas suntikan busulfan dilakukan. Hasil kajian menunjukkan kepekatan sperma, skor indeks spermatogenesis, diameter tubul seminiferus dan ketinggian sel germa menurun di dalam kumpulan oligospermia teraruh busulfan. Status apoptosis turut meningkat secara signifikan. Suplementasi EBN telah meningkatkan kepekatan sperma, skor indeks spermatogenesis, ketinggian sel germa serta pengekspresan gen p38 dan MAPK14 secara signifikan. Suplementasi EBN juga menurunkan status apoptosis secara kebergantungan dos. Kesimpulannya, suplementasi EBN harian mempunyai kesan perlindungan terhadap oligospermia teraruh busulfan dengan meningkatkan penghasilan sperma, memelihara ciri histologi testis, mengurangkan apoptosis dan meningkatkan pengekspresan gen p38 dan MAPK14.

 

Kata kunci: Kepekatan sperma; oligospermia; p38; sarang burung walit; spermatogenesis

 

RUJUKAN

Albishtue, A.A., Yimer, N., Zakaria, M.Z.A., Abubakar, A.A. & Almhanawi, B.H. 2019a. Effects of EBN on embryo implantation, plasma concentrations of reproductive hormones, and uterine expressions of genes of PCNA, steroids, growth factors and their receptors in rats. Theriogenology 126: 310-319.

Albishtue, A.A., Yimer, N., Zakaria, M.Z.A., Haron, A.W., Babji, A.S., Abubakar, A.A., Baiee, F.H., Almhanna, H.K. & Almhanawi, B.H. 2019b. The role of edible bird’s nest and mechanism of averting lead acetate toxicity effect on rat uterus. Veterinary World 12(7): 1013-1021.

Aswir, A.R. & Wan Nazaimoon, W. 2011. Effect of edible bird's nest on cell proliferation and tumor necrosis factor-alpha (TNF-α) release in vitro. International Food Research Journal 18(3): 1123-1127.

Babji, A., Nurfatin, M., Etty Syarmila, I. & Masitah, M. 2015. Secrets of edible bird nest. UTAR Agriculture Science Journal 1(1): 32-37.

Barbagallo, F., La Vignera, S., Cannarella, R., Aversa, A., Calogero, A.E. & Condorelli, R.A. 2020. Evaluation of sperm mitochondrial function: A key organelle for sperm motility. Journal of Clinical Medicine 9(2): 363.

Bonney, E.A. 2017. Mapping out p38MAPK. American Journal of Reproductive Immunology 77(5): e12652.

Budin, S.B., Kho, J.H., Lee, J.H., Ramalingam, A., Jubaidi, F.F., Latif, E.S., Zainalabidin, S., Taib, I.S. & Mohamed, J. 2017. Low-dose nicotine exposure induced the oxidative damage of reproductive organs and altered the sperm characteristics of adolescent male rats. The Malaysian Journal of Medical Sciences 24(6): 50-57.

Cannarella, R., Precone, V., Guerri, G., Busetto, G.M., Di Renzo, G.C., Gerli, S., Manara, E., Dautaj, A., Bertelli, M. & Calogero, A.E. 2020. Clinical evaluation of a custom gene panel as a tool for precision male infertility diagnosis by next-generation sequencing. Life (Basel) 10(10): 242.

Careena, S., Sani, D., Tan, S., Lim, C., Hassan, S., Norhafizah, M., Kirby, B.P., Ideris, A., Stanslas, J. & Bin Basri, H. 2018. Effect of edible bird’s nest extract on lipopolysaccharide-induced impairment of learning and memory in wistar rats. Evidence-Based Complementary and Alternative Medicine 2018: 9318789.

Chen, X., Liang, M. & Wang, D. 2018. Progress on the study of the mechanism of busulfan cytotoxicity. Cytotechnology 70: 497-502.

Chyra-Jach, D., Kaletka, Z., Dobrakowski, M., Machoń-Grecka, A., Kasperczyk, S., Bellanti, F., Birkner, E. & Kasperczyk, A. 2020. Levels of macro-and trace elements and select cytokines in the semen of infertile men. Biological Trace Element Research 197: 431-439.

Cuenda, A. & Sanz-Ezquerro, J.J. 2017. P38γ and P38δ: From spectators to key physiological players. Trends in Biochemical Sciences 42(6): 431-442.

Dobutr, T., Kantamala, W., Phimwapi, S., Jangpromma, N., Tippayawat, P., Boonlue, S., Daduang, J., Klaynongsruang, S., Poopornchai, S. & Daduang, S. 2022. The effects of edible bird’s nest on t-lymphocyte proliferation, secondary lymphoid organs, and interleukin-2 production. Journal of Functional Foods 90: 104977.

Falk, T., Yue, X., Zhang, S., Mccourt, A.D., Yee, B.J., Gonzalez, R.T. & Sherman, S.J. 2011. Vascular endothelial growth factor-b is neuroprotective in an in vivo rat model of Parkinson's disease. Neuroscience Letters 496(1): 43-47.

Hamzah, Z., Ibrahim, N.H., Sarojini, J., Hussin, K., Hashim, O. & Lee, B-B. 2013. Nutritional properties of edible bird nest. Journal of Asian Scientific Research 3(6): 600-607.

Hosseini, A.N., Khaki, A., Akbari, G. & Ghaffari, N.M. 2014. The effect of busulfan on body weight, testis weight and MDA enzymes in male rats. International Journal of Women's Health and Reproduction Sciences 2(5): 316-319.

Ibrahim, S.F., Osman, K., Das, S., Othman, A.M., Majid, N.A. & Rahman, M.P.A. 2008. A study of the antioxidant effect of alpha lipoic acids on sperm quality. Clinics 63: 545-550.

Jaffar, F.H.F., Osman, K., Hui, C.K., Zulkefli, A.F. & Ibrahim, S.F. 2021. Edible bird’s nest supplementation improves male reproductive parameters of Sprague Dawley rat. Frontiers in Pharmacology 12: 631402.

Jaffar, F.H.F., Ibrahim, S.F., Ismail, M.I., Nang, C.F. & Faezah, S. 2019. Development of sperm separation system using electrical current for bull. Jurnal Sains Kesihatan Malaysia 17(1): 99-105.

Jiang, S., Xu, Y., Fan, Y., Hu, Y., Zhang, Q. & Su, W. 2022. Busulfan impairs blood–Testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9. Andrology 10(2): 377-391.

Kamaruzaman, K.A. & Noor, M. 2017. Gynura procumbens leaf improves blood glucose level, restores fertility and libido of diabetic-induced male rats. Sains Malaysiana 46(9): 1471-1477.

Khorsandi, L., Daneshi, E., Orazizadeh, M., Absalan, F., Saremy, S. & Jafaee Sough, A. 2017. Ameliorating effect of β-carotene on gene expression alteration in spermatozoon cultured with titanium oxide. Anatomical Sciences Journal 14(1): 1-10.

Kim, S-C., Stice, J.P., Chen, L., Jung, J.S., Gupta, S., Wang, Y., Baumgarten, G., Trial, J. & Knowlton, A.A. 2009. Extracellular heat shock protein 60, cardiac myocytes, and apoptosis. Circulation Research 105(12): 1186-1195.

Lai, D., Wang, F., Yao, X., Zhang, Q., Wu, X. & Xiang, C. 2015. Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure. Journal of Translational Medicine 13: 55.

Lestari, S.W., Aditya, D., Pratama, G., Sumapradja, K. & Margiana, R. 2019. A modification of johnson score as predictive value of sperm retrieval in non-obstructive azoospermia infertile men. AIP Conference Proceedings 2092: 030019.

Li, B., He, X., Zhuang, M., Niu, B., Wu, C., Mu, H., Tang, F., Cui, Y., Liu, W. & Zhao, B. 2018. Melatonin ameliorates busulfan-induced spermatogonial stem cell oxidative apoptosis in mouse testes. Antioxidants & Redox Signaling 28(5): 385-400.

Li, M.W., Mruk, D.D. & Cheng, C.Y. 2009. Mitogen-activated protein kinases in male reproductive function. Trends in Molecular Medicine 15(4): 159-168.

Luo, D., He, Z., Yu, C. & Guan, Q. 2022. Role of p38 MAPK signalling in testis development and male fertility. Oxidative Medicine and Cellular Longevity 2022: 6891897.

Ma, F. & Liu, D. 2012. Sketch of the edible bird's nest and its important bioactivities. Food Research International 48(2): 559-567.

Mao, J., Pennington, K.A., Talton, O.O., Schulz, L.C., Sutovsky, M., Lin, Y. & Sutovsky, P. 2018. In utero and postnatal exposure to high fat, high sucrose diet suppressed testis apoptosis and reduced sperm count. Scientific Reports 8: 7622.

Martins, R.V., Silva, A.M., Duarte, A.P., Socorro, S., Correia, S. & Maia, C.J. 2021. Natural products as protective agents for male fertility. BioChem 1(3): 122-147.

Maurya, N.K. 2019. Role of nutrition and associated factors in oligospermia (low sperm count). Infertility 5: 9.

Mehraein, F., Talebi, R., Jameie, B., Joghataie, M.T. & Madjd, Z. 2011. Neuroprotective effect of exogenous melatonin on dopaminergic neurons of the substantia nigra in ovariectomized rats. Iranian Biomedical Journal 15(1-2): 44-50.

Mendes, T.B., Paccola, C.C., De Oliveira Neves, F.M., Simas, J.N., Da Costa Vaz, A., Cabral, R., Vendramini, V. & Miraglia, S.M. 2016. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty. Reproduction 152(1): 23-35.

Nabi, A., Khalili, M., Halvaei, I. & Roodbari, F. 2014. Prolonged incubation of processed human spermatozoa will increase DNA fragmentation. Andrologia 46(4): 374-379.

Nasimi, P., Tabandeh, M.R. & Roohi, S. 2018. Busulfan-mediated oxidative stress and genotoxicity decrease in sperm of Satureja Khuzestanica essential oil-administered mice. Systems Biology in Reproductive Medicine 64(5): 348-357.

OECD. 2008. Test No. 407: Repeated Dose 28-Day Oral Toxicity Study in Rodents.

Ogunlaja, A. 2020. Fluted pumpkin seeds protect against busulfan-induced oxidative stress and testicular injuries in adult mice. Drug Chem. Toxicol. 45(1): 22-32.

Panahi, M., Keshavarz, S., Rahmanifar, F., Tamadon, A., Mehrabani, D., Karimaghai, N., Sepehrimanesh, M. & Aqababa, H. 2015. Busulfan induced azoospermia: Stereological evaluation of testes in rat. Veterinary Research Forum. 6(4): 273-278.

Pergialiotis, V., Prodromidou, A., Frountzas, M., Korou, L.M., Vlachos, G.D. & Perrea, D. 2016. Diabetes mellitus and functional sperm characteristics: A meta-analysis of observational studies. Journal of Diabetes and Its Complications 30(6): 1167-1176.

Roh, K-B., Lee, J., Kim, Y-S., Park, J., Kim, J-H., Lee, J. & Park, D. 2012. Mechanisms of edible bird's nest extract-induced proliferation of human adipose-derived stem cells. Evidence-Based Complementary and Alternative Medicine 2012: 797520.

Saygin, M., Caliskan, S., Karahan, N., Koyu, A., Gumral, N. & Uguz, A. 2011. Testicular apoptosis and histopathological changes induced by a 2.45 GHz electromagnetic field. Toxicology and Industrial Health 27(5): 455-463.

Sharma, A. 2017. Male infertility; Evidences, risk factors, causes, diagnosis and management in human. Annals of Clinical and Laboratory Research 05(03). doi: 10.21767/2386-5180.1000188

Skurikhin, E., Pakhomova, A., Pershina, O., Ermolaeva, L., Ermakova, N., Krupin, V., Pan, E., Kudryashova, A., Rybalkina, O.Y. & Zhdanov, V. 2017. Regenerative potential of stem and progenitor cells from ischemic testes of C57bl/6 mice in culture and in the model of spermatogenesis suppression caused by busulfan. Bulletin of Experimental Biology and Medicine 162(3): 400-405.

Sohrabipour, S., Jafari, A., Kamalinejad, M., Sarrafnejd, A., Shahrestany, T. & Sadeghipour, H-R. 2013. The role of flaxseed and vitamin E on oxidative stress in prepubertal rats with experimental varicocele: An experimental study. Iranian Journal of Reproductive Medicine 11(6): 459-466.

Sui, X., Kong, N., Ye, L., Han, W., Zhou, J., Zhang, Q., He, C. & Pan, H. 2014. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Letters 344(2): 174-179.

Terazawa, S. & Shimoda, H. 2020. Keratinocyte proliferative and wound healing effects of edible bird’s nest extract on human skin. Int. J. Biomed. Sci. 16: 43-51.

Teves, M.E. & Roldan, E.R. 2022. Sperm bauplan and function and underlying processes of sperm formation and selection. Physiological Reviews 102(1): 7-60.

Vahdati, A., Fathi, A.R., Nasimi, P. & Saki, G. 2015. Busulfan induces apoptotic and cytotoxic effects on testis and epididymal sperm of adult male mouse following low dose treatment. Int. J. Biol. 5: 70-78.

Wang, J. 2018. Neutrophils in tissue injury and repair. Cell and Tissue Research 371: 531-539.

Yew, M.Y., Koh, R.Y., Chye, S.M., Othman, I. & Ng, K.Y. 2014. Edible bird’s nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells. BMC Complementary and Alternative Medicine 14(1): 391.

Yi, S., Feng, Y., Wang, Y. & Ma, F. 2023. Sialylation: Fate decision of mammalian sperm development, fertilization, and male fertility. Biology of Reproduction 109(2): 137-155.

Zainab, H., Nur Hulwani, I., Jeyaraman, S., Kamarudin, H., Othman, H. & Lee, B.B. 2013. Nutritional properties of edible bird nest. Journal of Asian Scientific Research 3(6): 600-607.

Zainal Abidin, F., Hui, C.K., Luan, N.S., Mohd Ramli, E.S., Hun, L.T. & Abd Ghafar, N. 2011. Effects of edible bird's nest (EBN) on cultured rabbit corneal keratocytes. BMC Complementary and Alternative Medicine 11(1): 94-103.

Zeng, Q., Yi, H., Huang, L., An, Q. & Wang, H. 2019. Long-term arsenite exposure induces testicular toxicity by redox imbalance, G2/M cell arrest and apoptosis in mice. Toxicology 411: 122-132.

Zhang, X-D., Chen, M-Y., Gao, Y., Han, W., Liu, D-Y. & Huang, G-N. 2011. The effects of different sperm preparation methods and incubation time on the sperm DNA fragmentation. Human Fertility 14(3): 187-191.

Zhao, R., Li, G., Kong, X-J., Huang, X-Y., Li, W., Zeng, Y-Y. & Lai, X-P. 2016. The improvement effects of edible bird’s nest on proliferation and activation of B lymphocyte and its antagonistic effects on immunosuppression induced by cyclophosphamide. Drug Design, Development and Therapy 10: 371-381.

 

*Pengarang untuk surat-menyurat; email: timi@ukm.edu.my

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

   

sebelumnya