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University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using male albino mice Suhera M. Aburawi 1 , Habiba A. El jaafari 2 , Soad A. Treesh 3 , Abdulssalam M. Abu-Aisha 1 , Faisal S. Alwaer 1 , Reda A. Eltubuly 1 , Medeha Elghedamsi 1 1 , Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy; 2 , Zoology Department, Science Faculty;

University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

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Page 1: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

University Of TripoliFaculty Of Pharmacy

Department Of Pharmacology and Clinical Pharmacy

Selenium effect on infertility induced by formaldehyde using male albino

mice

Suhera M. Aburawi1, Habiba A. El jaafari2, Soad A. Treesh3, Abdulssalam M. Abu-Aisha1, Faisal S. Alwaer1, Reda A. Eltubuly1, Medeha

Elghedamsi1

1, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy; 2, Zoology

Department, Science Faculty; 3, Department of Histology and medical genetics, Faculty of

Medicine - University of Tripoli

Page 2: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Male InfertilityMeans that men are not able to conceive a

child even through they have had frequent.Male Infertility is due to low sperm

production, misshapen or immobile sperm or blockages that prevent the delivery of sperm (McPhee et al., 2012).

is the inability of a sexually active, non-contracepting couple to achieve pregnancy in one year (WHO, 2000).

Infertility is a source of psychological, and sometimes social, stress on parents who desire to have children.

Page 3: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Male Reproductive Toxicity of Formaldehyde

Formaldehyde is an important precursor to many other materials and chemical compounds (Reuss et al., 2002).

The medical uses of formaldehyde are limited, but focused especially on laboratory use (Zahra, 2007).

High dose of formaldehyde resulted in pathological changes in the seminiferous tubules ( STs ) of adult rats and mice (Tang et al., 2003 ).

Page 4: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Selenium

is an essential trace mineral element for human and animals. Is found in soil, rocks and consequently may then accumulate in plants (Yang and Zhou, 1994).

naturally present in some foods, such as : Fish, Shellfish, Red meat, Offal, Chicken, Liver, Garlic, Eggs, Brazil Nuts and Grains (Escott-Stump, 2008).

plays an important role in a number of biological processes (Combs and Combs, 1986).

Page 5: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

act by trapping free oxygen radicals and scavenging and converting free radicals into stable compounds (Sieja and Talerezyk, 2004).

is present in selenoenzymes, such as glutathione peroxidase and thioredoxin reductase, which indirectly reduce certain oxidized molecules and protect DNA and other cellular components from oxidative damage (Valko, et al., 2006).

is essential for sperm function and male fertility. Selenium deficiency has been linked to reproductive problems in rats, mice, chickens, pigs, sheep, and cattle (Combs and

Combs, 1986).

Page 6: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Goal of the work

To investigate the effect of selenium on male infertility induced by formaldehyde using

male albino mice

Page 7: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Treatment groupsN = 8 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6

Group I Water for injection (5ml/day)

Water for injection (5ml/day)

Water for injection (5ml/day)

Water for injection (5ml/day)

Water for injection (5ml/day)

Scoring

Group II Selenium100μg/kg

Selenium100μg/kg

Selenium100μg/kg

Selenium100μg/kg

Selenium100μg/kg

Scoring

Group III

(Peng et al., 2006)

Formaldehyde30 mg/kg

Formaldehyde30 mg/kg

Formaldehyde30 mg/kg

Formaldehyde30 mg/kg

Formaldehyde30 mg/kg

Scoring

Group IV (prophylaxis)

Formaldehyde+ Selenium

Formaldehyde+ Selenium

Formaldehyde+ Selenium

Formaldehyde+ Selenium

Formaldehyde+ Selenium

Scoring

Group V( curative) Formaldehyde Formaldehyde Formaldehyde Formaldehyde Formaldehyde Selenium

Selenium Selenium Selenium Selenium Selenium Scoring

Design of the workSelenium effect on infertility induced by formaldehyde using

male albino mice

Page 8: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Sperm Counting

Counting of mice sperm is done by Hematocytometer slide.

Page 9: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Results and Discussion

Page 10: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

Sp

erm

cou

nt

x 1

0^

6

* a

*, significantly different from SE at p≤0.049a, significantly different from SE at p≤0.063

Page 11: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

0

50

100

150

200

250T

ota

l -

mo

tile

- n

on

mo

tile

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*, a, Significantly different compared to saline at p≤0.05b, c, Significantly different compared to selenium at p≤0.05

a

a

cb

b

c

Page 12: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

0

100

200

300

400

500

600T

ota

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he

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*, Significantly different compared to formaldhyde at p≤0.05a, Significantly different compared to selenium+formaldhyde (prophylaxis) at p≤0.05

* *,a

****

Page 13: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

0

10

20

30

40

50

60

70

80

90

100M

orp

ho

log

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% h

ealt

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perm

co

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*,a*

*, significantly different compared to formaldhyde at p≤0.05a, significantly different from prophylaxis (formald-hyde+selenium at p≤0.05

**

Page 14: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

0

10

20

30

40

50

60

70

80

90

100%

mo

tile

sp

erm

*,a

a

*, significantly different from saline at p≤0.05a, significantly different from formaldhyde at p≤0.05

*,a

Page 15: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using
Page 16: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using
Page 17: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using
Page 18: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using
Page 19: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using
Page 20: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Formaldehyde

In formaldehyde reproductive toxicity, there were more male than female exposure studies.

This may be because effects on male reproduction are more readily observable and require fewer invasive procedures (Duong et al., 2011).

Page 21: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Formaldehyde significantly decreased the activities of superoxide dismutase and glutathione peroxidase (Shi et al., 2012).

Reactive oxygen species-mediated oxidative damage resulting from formaldehyde exposure has been detected in reproductive tissues (Im et al., 2006).

Formaldehyde is genotoxic, inducing:• Chromosomal aberrations (Natarajan et al., 1983). • DNA breakage (Wang et al., 2006a).• DNA-protein crosslinks (Peng et al., 2006; Wang et al., 2006c).• Mediated aberrant DNA methylation

which has been associated with male gametogenic defects (Navarro-Costa et al., 2010).

Page 22: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) are involved in the maturation of spermatogenic cells, testis and spermatozoa and with energy metabolism of spermatozoa.• Formaldehyde decrease the activity of

SDH in mice testicular (Xie et al., 2003). • SDH activity was positively correlated

with sperm cell counts, and negatively correlated with the abnormal rate of sperm heads (Tang et al., 2003).

Page 23: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Formaldehyde exposure decreased serum testosterone levels were in male mice and rats (Chowdhury et al., 1992; Ozen et al., 2005; Zhou et al., 2006), to leading to disruption of male reproductive function.

Formaldehyde treatment activates necrosis factor-κB (NF-κB) (Shi et al., 2012).

Page 24: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Selenium

There is significant positive correlations in selenium concentration between different reproductive organs, (Oldereid et al., 1998)• Testis having the highest concentrations.

In selenium-deficient rats, flagellar disorganization during spermiogenesis and post-testicular sperm development were observed. • loss of male fertility in selenium deficiency

results from the sequential development of sperm defects expressed during both spermiogenesis and maturation in the epididymis (Olson et al., 2004). 

Page 25: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Selenium(Shi et al., 2012)• counteracted formaldehyde-induced

oxidative stress,• ameliorated DNA–protein cross-links and • attenuated the activation of necrosis factor

–κB.

Page 26: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Conclusion

Page 27: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Formaldehyde toxicitySperm count is not changed

Percentage of motile sperm was not changed.

Unhealthy sperm was increased, while healthy sperm was decreased.

Formaldehyde produces degeneration/damage to male mice genital system.

Page 28: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Selenium alone produce the following compared to healthy group Sperm count is increased.Volume of seminal fluid is larger .Percentage of motile sperm is increased.

Selenium has prophylactic and curative effects against formaldehyde-induce genital system toxicity.

Future work

Page 29: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

•Chowdhury AR, Gautam AK, Patel KG, Trivedi HS. (1992). Steroidogenic inhibition in testicular tissue of formaldehyde exposed rats. Indian J Physiol Pharmacol.; 36:162–168. •Combs GF, Combs BS. (1986). The Role of Selenium in Nutrition. London: Academic Press; 206-312.•Duong A., Steinmaus C., McHale C.M., Vaughan C.P., Zhang L., (2011). Mutat Res.; 728(3): 118–138. •Escott-Stump S, ed. Nutrition and Diagnosis-Related Care. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008.•Im H, Oh E, Mun J, Khim JY, Lee E, Kang HS, Kim E, Kim H, Won NH, Kim YH, Jung WW, Sul D. (2006). Evaluation of toxicological monitoring markers using proteomic analysis in rats exposed to formaldehyde. J Proteome Res.; 5:1354–1366.•McPhee SJ, et al. Current Medical Diagnosis & Treatment 2012. 51st ed. New York, N.Y.: The McGraw-Hill Companies. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=1. Accessed July 20, 2012•Natarajan AT, Darroudi F, Bussman CJ, van Kesteren-van Leeuwen AC. (1983). Evaluation of the mutagenicity of formaldehyde in mammalian cytogenetic assays in vivo and vitro. Mutat Res.; 122:355–360. •Navarro-Costa P, Nogueira P, Carvalho M, Leal F, Cordeiro I, Calhaz-Jorge C, Goncalves J, Plancha CE. (2010). Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum Reprod.; 25:2647–2654.•Oldereid NB, Thomassen Y, Purvis K.(1998). Selenium in human male reproductive organs. Hum Reprod.; 13(8): 2172-2176.•Olson G.E., Winfrey V.P., Hill K.E., Burk R.F. (2004). Sequential development of flagellar defects in spermatids and epididymal spermatozoa of selenium-deficient rats. Reproduction. 127 335–342. •Ozen O.A., Akpolat N., Songur A., Kus I., Zararsiz I., Ozacmak V.H., Sarsilmaz M. (2005). Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes: an immunohistochemical study.Toxicol Ind Health.; 21:249–254.•Peng G, Yang X, Zhao W. (2006). Study of DPC Induced by Liquid Formaldehyde in the Liver and Testicles of Mice. J Med Res.; 35:9–12.•Peng G, Yang X, Zhao W. (2006). Study of DPC Induced by Liquid Formaldehyde in the Liver and Testicles of Mice. J Med Res.; 35:9–12.•Reuss G., Disteldorf W., Gamer A.O., Hilt A. (2002) "Formaldehyde" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. Doi:10.1002/14356007.a11_619.•Shi Y-Q, Chen X., Dai J., Jiang Z-F., Li N., Zhang B-Y., Zhang Z-B. (2012 ). Selenium pretreatment attenuates formaldehyde-induced genotoxicity in A549 cell lines. Toxicol Ind Health. November 16, 2012, doi:10.1177/0748233712466129•Sieja K, Talerezyk M. (2004). Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol.; 93:227-320.•Tang M, Xie Y, Yi Y, Wang W. (20003). Effects of formaldehyde on germ cells of male mice. Wei Sheng Yan Jiu.; 32:544–548. •Valko M, Rhodes CJ, Moncol J, et al. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact.;160:1-40.•Wang N, Yang Y, Zhang L, Ye L. (2006c) Reproductive toxicity of formaldehyde on male mice. Community Medical Journal.2006c;4:13–15.•Wang X, Duan L, Li C. (2006a). Study on formaldehyde-induced DNA damage in mice testicular cells. J Environ Health.; 23:128–131.•World Health Organization. WHO Manual for the Standardised Investigation and Diagnosis of the Infertile Couple. Cambridge: Cambridge University Press, 2000•Xie Y, Yi Y, Tang M. (2003). Toxicity of formaldehyde on germ cells of male mice. J Environ Health.; 20:84–85.•Yang G., Zhou R. (1994) Further observations on the human maximum safe dietary selenium intake in a seleniferous area in China. Journal of Trace Elements and Electrolytes in Health and Disease. 8: 159-165.•Zahra T., Parviz T., Simin F., Mehdi T. (2007). Effect of Formaldehyde Injection in Mice on Testis Function. International Journal of Pharmacology, 3: 421-424.DOI: 10.3923/ijp.2007.421.424 URL: http://scialert.net/abstract/?doi=ijp.2007.421.424•Zhou DX, Qiu SD, Zhang J, Wang ZY. (2006). Reproductive toxicity of formaldehyde to adult male rats and the functional mechanism concerned. Sichuan Da Xue Xue Bao Yi Xue Ban.; 37:566–569. 

References

Page 30: University Of Tripoli Faculty Of Pharmacy Department Of Pharmacology and Clinical Pharmacy Selenium effect on infertility induced by formaldehyde using

Thank You…