Alterations of Kiss 1 receptor, GnRH receptor and nuclear receptors of the hypothalamopituitary-ovarian axis following low dose bisphenol-A exposure in Wistar rats

다국어 초록 (Multilingual Abstract)

Bisphenol A is a chemical used primarily as a monomer in the production of polycarbonate plastics and epoxy resins. It is a synthetic chemical compound that is produced in billions of pounds annually, and tagged as an endocrine disruptor. Bisphenol A is a high production synthetic chemical compound that is used in the production of many consumables and equipments of daily consumption and use by man. Growing interest in possible health threats posed by endocrine disrupting chemicals (bisphenol-A inclusive), as these substances are in our environment, food, and many consumer products. Therefore, this study aims to determine bisphenol-A effects on the hypothalamo-pituitary-ovarian axis, and role of melatonin in this regard. Forty-two Wistar rats were bred, grouped into 7, with each group consisting of 6 rats. Experimental groups were administered low and high doses of bisphenol-A and melatonin, starting from day 19, and was continued for 7 weeks orally. They were left to develop into full adults and were sacrificed on day 120±4 days. Blood samples, hypothalamus, pituitary and ovarian tissues were excised for biochemical and tissue antioxidants assays as well as genetic studies. Results show elevated gonadotropin and androgen levels. There was disruption of reactive oxygen species in the ovarian tissues, as well as alterations in the expression of genes that regulate reproduction at the hypothalamus and pituitary levels. Conclusion of early exposure to bisphenol-A is associated with prolonged duration of disruption of reproductive functions in female Wistar rats, which persist long after cessation of the exposure. Melatonin antioxidant effects give some promising outturns against bisphenol-A induced toxicities.

목차 (Table of Contents)

• Introduction Materials and Methods Results Discussion ORCID Author Contributions Conflicts of Interest Acknowledgements References

참고문헌 (Reference)

1 Balakrishnan N, "Vitamin E modulates the oxidant-antioxidant imbalance of BPA induced oxidative stress in albino rats" 7 : 900-906, 2018

2 Mohammad-Amin Abdollahifar, "Vitamin C restores ovarian follicular reservation in a mouse model of aging" 대한해부학회 52 (52): 196-203, 2019

3 Shankar A, "Urinary bisphenol a levels and measures of obesity: results from the national health and nutrition examination survey 2003-2008" 2012 : 965243-, 2012

4 Lassen TH, "Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality" 122 : 478-484, 2014

5 Melzer D, "Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women" 125 : 1482-1490, 2012

6 Mohamad Zaid SS, "Tualang honey protects against BPA-induced morphological abnormalities and disruption of ERα, ERβ, and C3 mRNA and protein expressions in the uterus of rats" 2015 : 202874-, 2015

7 Lunardi D, "Transcriptomic analysis of bottlenose dolphin (Tursiops truncatus)skin biopsies to assess the effects of emerging contaminants" 114 : 74-79, 2016

8 FAO, "Toxicological and Health Aspects of Bisphenol A Report of Joint FAO/WHO Expert Meeting" WHO 60-, 2011

9 Aydin V, "The effects of antioxidant melatonin on rat ovary neonatal exposure to bisphenol A" 19 : 33-37, 2017

10 Liang H, "The association between exposure to environmental bisphenol A and gonadotropic hormone levels among men" 12 : e0169217-, 2017

11 Kamel AH, "The adverse effects of bisphenol A on male albino rats" 79 : 6-, 2018

12 Elgawish RA, "Protective role of lycopene against metabolic disorders induced by chronic bisphenol A exposure in rats" 27 : 9192-9201, 2020

13 El Morsy EM, "Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats" 39 : 1066-1078, 2020

14 Perera F, "Prenatal bisphenol a exposure and child behavior in an inner-city cohort" 120 : 1190-1194, 2012

15 Jones BA, "Perinatal BPA exposure demasculinizes males in measures of affect but has no effect on water maze learning in adulthood" 61 : 605-610, 2012

16 Schug TT, "PPTOX III: environmental stressors in the developmental origins of disease--evidence and mechanisms" 131 : 343-350, 2013

17 Schwarzbauer J, "Occurrence and alteration of organic contaminants in seepage and leakage water from a waste deposit landfill" 36 : 2275-2287, 2002

18 Khan S, "Mitochondrial dysfunction induced by bisphenol A is a factor of its hepatotoxicity in rats" 31 : 1922-1934, 2016

19 Völkel W, "Metabolism and kinetics of bisphenol A in humans at low doses following oral administration" 15 : 1281-1287, 2002

20 Anderson RA, "Melatonin potentiates testosterone-induced suppression of luteinizing hormone secretion in normal men" 8 : 1819-1822, 1993

21 Othman AI, "Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity" 32 : 1537-1549, 2016

22 Reiter RJ, "Melatonin as an antioxidant: under promises but over delivers" 61 : 253-278, 2016

23 Anjum S, "Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse" 49 : 2849-2854, 2011

24 Wu HJ, "Melatonin ameliorates bisphenol A-induced DNA damage in the germ cells of adult male rats" 752 : 57-67, 2013

25 Chevrier J, "Maternal urinary bisphenol a during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study" 121 : 138-144, 2013

26 Ma S, "Lycopene reduces in utero bisphenol A exposure-induced mortality, benefits hormones, and development of reproductive organs in offspring mice" 25 : 24041-24051, 2018

27 Wang Z, "Low-dose bisphenol A exposure: a seemingly instigating carcinogenic effect on breast cancer" 4 : 1600248-, 2016

28 Vandenberg LN, "Low dose effects of bisphenol A: an integrated review of in vitro, laboratory animal, and epidemiology studies" 1 : e26490-, 2013

29 Hu KL, "Kisspeptin/kisspeptin receptor system in the ovary" 8 : 365-, 2018

30 Berhane TM, "Kinetic sorption of contaminants of emerging concern by a palygorskitemontmorillonite filter medium" 176 : 231-242, 2017

31 Geens T, "Intake of bisphenol A from canned beverages and foods on the Belgian market" 27 : 1627-1637, 2010

32 Gassman NR, "Induction of oxidative stress by bisphenol A and its pleiotropic effects" 58 : 60-71, 2017

33 Richter CA, "In vivo effects of bisphenol A in laboratory rodent studies" 24 : 199-224, 2007

34 Dhagga N, "Histological effects of bisphenol-A on reproductive organs of female Wistar rats" 5 : 152-162, 2017

35 Xiao C, "Hazards of bisphenol A (BPA) exposure: a systematic review of plant toxicology studies" 384 : 121488-, 2020

36 Meczekalski B, "Fertility in women of late reproductive age: the role of serum anti-Müllerian hormone (AMH) levels in its assessment" 39 : 1259-1265, 2016

37 Ziv-Gal A, "Evidence for bisphenol A-induced female infertility: a review (2007-2016)" 106 : 827-856, 2016

38 Maganhin CC, "Effects of melatonin on ovarian follicles" 166 : 178-184, 2013

39 Palanza P, "Effects of developmental exposure to bisphenol A on brain and behavior in mice" 108 : 150-157, 2008

40 Haroun MR, "Effect of vitamin C on bisphenol A induced hepato& nephrotoxicity in albino rats" 16 (16): 57-85, 2016

41 Satya Prasad Venugopal, "Effect of melatonin on the onset of puberty in male juvenile rats" 대한해부학회 52 (52): 286-295, 2019

42 Abecia JA, "Effect of exogenous melatonin on the ovary, the embryo and the establishment of pregnancy in sheep" 2 : 399-404, 2008

43 Helal EGE, "Effect of bisphenol A on the first generation of female rats from both parents treated with the same xenoestrogen" 64 : 389-394, 2016

44 Galloway T, "Daily bisphenol A excretion and associations with sex hormone concentrations:results from the InCHIANTI adult population study" 118 : 1603-1608, 2010

45 Olukole SG, "Chronic exposure of adult male Wistar rats to bisphenol A causes testicular oxidative stress: role of gallic acid" 54 : 14-21, 2020

46 vom Saal FS, "Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure" 24 : 131-138, 2007

47 Prasanth GK, "Bisphenol-A can inhibit the enzymatic activity of human superoxide dismutase" 19 : 268-277, 2013

48 Huo X, "Bisphenol-A and female infertility: a possible role of gene-environment interactions" 12 : 11101-11116, 2015

49 Adeyi AA, "Bisphenol-A (BPA) in foods commonly consumed in Southwest Nigeria and its human health risk" 9 : 17458-, 2019

50 Sharma M, "Bisphenol- A induced oxidative stress and its fertility aspects" 10 : 3519-3531, 2019

51 Almeida S, "Bisphenol A: food exposure and impact on human health" 17 : 1503-1517, 2018

52 Pivonello C, "Bisphenol A: an emerging threat to female fertility" 18 : 22-, 2020

53 Yamamoto T, "Bisphenol A in hazardous waste landfill leachates" 42 : 415-418, 2001

54 Zhou C, "Bisphenol A exposure inhibits germ cell nest breakdown by reducing apoptosis in cultured neonatal mouse ovaries" 57 : 87-99, 2015

55 Grasselli F, "Bisphenol A disrupts granulosa cell function" 39 : 34-39, 2010

56 Peretz J, "Bisphenol A and reproductive health: update of experimental and human evidence, 2007-2013" 122 : 775-786, 2014

57 Ullah A, "Bisphenol A analogues bisphenol B, bisphenol F, and bisphenol S induce oxidative stress, disrupt daily sperm production, and damage DNA in rat spermatozoa: a comparative in vitro and in vivo study" 35 : 294-303, 2019

58 Leem YH, "BPA-toxicity via superoxide anion overload and a deficit in β-catenin signaling in human bone mesenchymal stem cells" 32 : 344-352, 2017

59 Bae S, "Associations of bisphenol A exposure with heart rate variability and blood pressure" 60 : 786-793, 2012

60 vom Saal FS, "An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment" 113 : 926-933, 2005

61 Elwakeel SHB, "Ameliorative effect of melatonin and quercetin against bisphenol A induced reproductive toxicity in male albino mice" 33 : 31-64, 2018

62 Saadeldin IM, "Ameliorative effect of ginseng extract on phthalate and bisphenol A reprotoxicity during pregnancy in rats" 25 : 21205-21215, 2018

63 Kaur S, "Alleviating impact of hydroethanolic Murraya koenigii leaves extract on bisphenol A instigated testicular lethality and apoptosis in mice" 52 : e13504-, 2020