The Effect of Ajwa Dates Fruit Extract on Follicle Stimulating Hormone (FSH), Graafian Follicle and Endometrial Thickness in Female Rats Exposed to Arsenic

Herdhika Ayu Retno Kusumasari


Background: Arsenic exposure in humans can disrupt the reproductive system and reproductive organs in women, which can cause interference hormonal and fertility disorders. The pathogenesis of arsenic causes oxidative damage to the organs and reproductive system due to an imbalance between Reactive Oxygen Species (ROS) and antioxidants in the body. Ajwa dates contain powerful antioxidants that act as scavenger ROS as well as inhibit lipid peroxidase which stop reactions associated with oxidative stress. Objective: This study aims to determine the effect of Ajwa date extract on Follicle Stimulating Hormone (FSH) levels, Graafian follicle and endometrial thickness in female rats exposed to Arsenic Trioxide (As2O3) for 30 days. Methods : Experimental laboratory with 5 treatment groups, negative control group (without arsenic exposure), positive control (3 mg/kg BW arsenic), T1 (arsenic 3 mg/kg BW + date extract 2ml / kg BW), T2 (arsenic 3 mg / kg BW + date extract 4ml / kg BW), and T3 (arsenic 3 mg / kg BW + date extract 8ml / kg body weight). Results: Arsenic exposure significantly reduced FSH levels, Graafian follicle count and endometrial thickness. Conclusion: The administration of Ajwa date extract could significantly provide antioxidant protection in the treatment group with an increase in FSH levels, Graafian follicle count and endometrial thickness.

Full Text:



Arsenic [homepage in the internet] World Health Organization (WHO);2015 [updated 2018 Februari 15; cited 2020 Januari 16].Available from :

Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, et al. Arsenic: Toxicity, oxidative stress and human disease. J Appl Toxicol. 2011;31(2):95–107

Flora SJS. Handbook of arsenic toxicology. Academic Press; 2014.

Substance Priority List | ATSDR [Internet]. Agency for Toxic Substances and Disease Registry. 2017. Available from:

Hart RJ. Physiological aspects of female fertility: Role of the environment, modern lifestyle, and genetics. Physiol Rev. 2016;96(3):873–909.

Sengupta P, Banerjee R, Nath S, Das S, Banerjee S. Metals and female reproductive toxicity. Hum Exp Toxicol. 2015;34(7):679–97

Sun HJ, Xiang P, Luo J, Hong H, Lin H, Li HB, et al. Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine systems in humans: A review. Environ Int [Internet]. 2016;95:61–8. Available from:

Watson WH, Yager JD. Arsenic: Extension of its endocrine disruption potential to interference with estrogen receptor-mediated signaling. Toxicol Sci. 2007;98(1):1–4.

Abdi F, Roozbeh N, Mortazavian AM. Effects of date palm pollen on fertility: Research proposal for a systematic review. BMC Res Notes. 2017;10(1):1–5

Saryono S, Dwi M, Rahmawati E. Effects of Dates Fruit (Phoenix Dactylifera L.) in the Female Reproductive Process. 2018;03(October):1630–3. Available from:

Ahmed A, Arshad MU, Saeed F, Ahmed RS, Chatha SAS. Nutritional probing and HPLC profiling of roasted date pit powder. Pakistan J Nutr. 2016;15(3):229–37

Al-Yahya M, Raish M, AlSaid MS, Ahmad A, Mothana RA, Al-Sohaibani M, et al. ‘Ajwa’ dates (Phoenix dactylifera L.) extract ameliorates isoproterenol-induced cardiomyopathy through downregulation of oxidative, inflammatory and apoptotic molecules in rodent model. Phytomedicine. 2016;23(11):1240–8.

Ben Abdallah F, Dammak I, Mallek Z, Attia H, Hentati B, Ammar-Keskes L. Effects of date seed oil on testicular antioxidant enzymes and epididymal sperm characteristics in male mice. Andrologia. 2009;41(4):229–34.

Al-Rasheed NM, Attia HA, Mohamad RA, Al-rasheed NM, Al-amin MA, Al-onazi A. Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor-??1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats. Hindawi Publ Corp Evidence-Based Complement Altern Med. 2015;Volume 201:19 pages.

Vayalil PK. Antioxidant and antimutagenic properties of aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae). J Agric Food Chem. 2002;50(3):610–7.

Daramola OO, Oyeyemi WA, Beka FU, Ofutet EA. Protective effects of aqueous extract of citrullus lanatus fruit on reproductive functions and antioxidant activities in arsenic-treated male Wistar rats. African J Biomed Res. 2018;21(1):65–72.

Sezer Z, Ekiz Yilmaz T, Gungor ZB, Kalay F, Guzel E. Effects of vitamin E on nicotine-induced lipid peroxidation in rat granulosa cells: Folliculogenesis. Reprod Biol. 2020;20(1):63–74.

Conti M, Chang RJ. Folliculogenesis, Ovulation, and Luteogenesis [Internet]. Seventh Ed. Vols. 2–2, Endocrinology: Adult and Pediatric. Elsevier Inc.; 2015. 2179-2191.e3 p. Available from:

Myers M, Britt KL, Wreford NGM, Ebling FJP, Kerr JB. Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 2004;127(5):569–80.

Chatterjee A, Chatterji U. Arsenic abrogates the estrogen-signaling pathway in the rat uterus. Reprod Biol Endocrinol. 2010;8:1–11

Mehta M, Hundal SS. Effect of sodium arsenite on reproductive organs of female Wistar rats. Arch Environ Occup Heal. 2016;71(1):16–25.

Bodwell JE, Gosse JA, Nomikos AP, Hamilton JW. Arsenic disruption of steroid receptor gene activation: complex Dose− Response effects are shared by several steroid receptors. Chemical research in toxicology. 2006 Dec 18;19(12):1619-29.

Liu C, Zhang X, Deng J, Hecker M, Al-Khedhairy A, Giesy JP, Zhou B. Effects of prochloraz or propylthiouracil on the cross-talk between the HPG, HPA, and HPT axes in zebrafish. Environmental science & technology. 2011 Jan 15;45(2):769-75.

Stafford DE. Altered hypothalamic-pituitary-ovarian axis function in young female athletes. Treatments in Endocrinology. 2005 Jun 1;4(3):147-54.

Marques P, Skorupskaite K, George JT, et al. Physiology of GNRH and Gonadotropin Secretion. [Updated 2018 Jun 19]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000-. Available from:

Sun HJ, Rathinasabapathi B, Wu B, Luo J, Pu LP, Ma LQ. Arsenic and selenium toxicity and their interactive effects in humans. Environment international. 2014 Aug 1;69:148-58.

Cabilla JP, Ronchetti SA, Duvilanski BH. Adverse effects induced by chromium VI, cadmium and arsenic exposure on hypothalamus-pituitary physiology. Biocell. 2016;40(1):15–8.

Ronchetti SA, Bianchi MS, Duvilanski BH, Cabilla JP. In Vivo and in Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland. Int J Toxicol. 2016;35(4):463–75.

Chattopadhyay S, Ghosh D. Role of dietary GSH in the amelioration of sodium arsenite-induced ovarian and uterine disorders. Reprod Toxicol [Internet]. 2010;30(3):481–8. Available from:

Kchaou W, Abbès F, Attia H, Besbes S. In vitro antioxidant activities of three selected dates from Tunisia (Phoenix dactylifera L.). J Chem. 2014;2014.

Khatun S, Maity M, Perveen H, Dash M, Chattopadhyay S. Spirulina platensis ameliorates arsenic-mediated uterine damage and ovarian steroidogenic disorder. Facets. 2018;3(1):736–53.

Yu H, Kuang M, Wang Y, Rodeni S, Wei Q, Wang W, et al. Sodium Arsenite Injection Induces Ovarian Oxidative Stress and Affects Steroidogenesis in Rats. Biol Trace Elem Res. 2019;189(1):186–93

Flora SJS. Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med. 2011;51(2):257–81.

Akram Z, Jalali S, Shami SA, Ahmad L, Batool S, Kalsoom O. Genotoxicity of sodium arsenite and DNA fragmentation in ovarian cells of rat. Toxicol Lett. 2009;190(1):81–5

Moshfegh F, Baharara J, Namvar F, Zafar-Balanezhad S, Amini E, Jafarzadeh L. Effects of date palm pollen on fertility and development of reproductive system in female Balb/C mice. J HerbMed Pharmacol. 2016;5(1):23–8.

Chuan-Rui Zhang, Saleh A. Aldosari, Polana S. P. V. Vidyasagar, Karun M. Nair and MGN. Antioxidant and Anti-in fl ammatory Assays Con fi rm Bioactive Compounds in Ajwa Date Fruit. J Agric Food Chem. 2013;

Bouayed J, Bohn T. Exogenous antioxidants - Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010;3(4):228–37.

Adaay MH, Mattar AG. Effect of Aqueous and Ethanolic Extracts of Tribulus terrestris, Phoenix dactylifera and Nasturtium officinale Mixture on Some Reproductive Parameters in Male Mice. Baghdad Sci J. 2012;9(4):640–50.

Wang A, Holladay SD, Wolf DC, Ahmed SA, Robertson JL. Reproductive and developmental toxicity of arsenic in rodents: A review. Int J Toxicol. 2006;25(5):319–31.

Hidayat H. Perbaikan Kinerja Reproduksi Akibat Pemberian Isoflavon dari Tanaman Kedelai. Bandung: FPMIPA Universitas Pendidikan Indonesia. 2014;

Faradina H, Biologi PS, Sains F, Teknologi DAN, Islam U, Uin N, et al. Efek Fitoestrogen Ekstrak Buah Kurma ( Phoenix dactylifera ) Ruthab Terhadap Tebal Endometrium Mencit ( Mus musculus ) Betina. 2018

Tahvilzadeh M, Hajimahmoodi M, Rahimi R. The Role of Date Palm (Phoenix dactylifera L) Pollen in Fertility: A Comprehensive Review of Current Evidence. J Evidence-Based Complement Altern Med. 2016;21(4):320–4


  • There are currently no refbacks.