SCIENTIFIC WRITING PROJECT...Synopsis of Writing Project 5 73. Scientific Writing Projects 2016 Summer Internship 11. Liu CY, Chou YC, Chao JC, Hsu CY, Cha TL, Tsao CW. The Association

71. Scientific Writing Projects Insert Page Summer Mentorship 2016

9th ANNUAL SUMMER MENTORSHIP IN

REPRODUCTIVE MEDICINE

JUNE 13th – JULY 29th, 2016

AMERICAN CENTER FOR REPRODUCTIVE MEDICINE

CLEVELAND CLINIC

SCIENTIFIC WRITING PROJECT

72. Index of Scientific Writing Project 2016 Summer Mentorship

INDEX OF SCIENTIFIC WRITING PROJECTS

PROJECT NO.

WRITING PROJECT TOPIC MENTOR(S) NO. OF

INTERNS DEADLINE

1 ROLE OF HEALTHY DIET IN SPERM

FUNCTION Rakesh Sharma, PhD 4 15-Aug-16

2 IMPACT OF DRUGS ON OOCYTE QUALITY Sajal Gupta, MD 5 15-Aug-16

3 DEFECTS OF MICROTUBULES

ASSOCIATED WITH MALE INFERTILITY Sezgin Ozgur Gunes, PhD 4 21-July-16

4 IMPACT OF ENDOCRINE DISRUPTING

COMPOUNDS ON CAUSING MALE INFERTILITY

Narasimhan Kothandaraman, PhD

4 15-Aug-16

5 PHTHALATES, SEMEN QUALITY AND MALE FERTILITY: AN EVIDENCE BASED REVIEW

Gulfam Ahmad, PhD 5 21-July-16

Synopsis of Writing Project

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73. Scientific Writing Projects 2016 Summer Internship

Rakesh Sharma, Ph.D. Associate Professor, Lerner College of Medicine

Project Staff & Coordinator American Center and Center for Reproductive Medicine

Cleveland Clinic Tel: 216-444-4350

E-mail: [email protected]

1. ROLE OF HEALTHY DIET IN SPERM FUNCTION

Background:

Studies suggest that appropriate nutritional modifications can improve the natural conception rate of

infertile couples. What you eat may have an impact on the quality of the sperm. Paternal nutrition

influences offspring metabolism in mammals. Metabolic gene expression was reported to be altered in

offspring generated via in vitro fertilization (IVF) using sperm obtained from animals consuming a control

or low-protein diet (19 or 10% protein, respectively). Paternal diet can also affect offspring metabolism

via information located in sperm. Higher consumption of a prudent dietary pattern (versus western or

mixed diet) was associated with higher sperm concentration and higher level of testosterone. Sperm

chromatin structure was inversely related to higher consumption of a prudent dietary pattern. So it makes

sense that the food choices could play a significant part in the ability to conceive. A healthy intake of

micronutrients—including vitamin C, E, folate, and zinc—can boost sperm DNA quality in older men.

Studies show that the more antioxidants and micronutrients that are present in the diet, the smaller the

risk for sperm with DNA damage, especially in older men. In fact, men ages 44 and older who ate the most

vitamin C had 20 percent less damage compared to men of the same age who consumed very little vitamin

C. Sub-fertile men who took zinc sulfates daily reported a 74 percent increase in total normal sperm count

after 26 weeks, compared to men who were treated with placebos. Foods rich in omega 3, alpha-linoleic

acid (ALA), fatty acid, lycopene may have beneficial effects on sperm quality.

Foods to be avoided are those rich in saturated fats, canned foods, fruits and vegetables laced with

pesticides. Increasing evidence indicates that offspring metabolic disorders can result from the father’s

diet, but the mechanism remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, show

sperm tRNA-derived small RNAs (tsRNAs), mainly from 5′ tRNA halves and ranging in size from 30 to 34

nucleotides, exhibit changes in expression profiles and RNA modifications. This represents a type of

[email protected]


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paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic

disorder.

Significance:

In this review we will discuss foods to embrace and those to avoid and list other assorted sperm killers to

avoid especially for men who may already be at risk of compromised male fertility health.

Outline:

1. Paternal diet and offspring metabolism

2. Role of transfer RNAs (tRNA) and small RNAs (sRNA) in sperm maturation

3. sRNA biogenesis and its dietary regulation during posttesticular sperm maturation

4. Role of small RNAs (sRNAs) in epigenetics

5. Effect of low protein diet on sRNAs

6. Healthy intake of vitamins in foods (vitamins A, C, E, B12)

7. Essential mineral in diet and sperm health

8. Foods good for the sperm (foods rich in folic acid, lycopene)

9. Super foods to increase sperm count (eggs, spinach, bananas, chocolate)

10. Foods to avoid (canned foods, saturated fats, pesticide laced fruits and vegetables, processed

meat)

11. Drink water and avoid alcohol

12. Diet and declining sperm quality (High fat, low protein diets)

13. Intake of healthy fruit and vegetables and sperm DNA fragmentation

Literature review:

Preliminary literature search has been done using resources of Cleveland Clinic Alumni Library. An

exhaustive literature review needs to be done before the article.

Journal:

To be decided.


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Suggested reading:

Resources of Cleveland Clinic Alumni Library

1. Qi Chen, Menghong Yan, Zhonghong Cao, Xin Li, Yunfang Zhang et al. Sperm tsRNAs contribute to

intergenerational inheritance of an acquired metabolic disorder. Science 31 Dec 2015: DOI:

10.1126/science.aad7977.

2. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW,

Sun F, Song L, Carone BR, Ricci EP, Li XZ, Fauquier L, Moore MJ, Sullivan R, Mello CC, Garber M,

Rando OJ. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in

mammals. Science. 2016; 22;351:391-6.

3. Jurewicz J, Radwan M, Sobala W, Radwan P, Bochenek M, Hanke W. Dietary Patterns and Their

Relationship With Semen Quality. Am J Mens Health. 2016 Jan 27. pii: 1557988315627139. [Epub

ahead of print]

4. Giahi L, Mohammadmoradi S, Javidan A, Sadeghi MR. Nutritional modifications in male infertility:

a systematic review covering 2 decades. Nutr Rev. 2016;74:118-30.

5. Gaskins AJ, Colaci DS, Mendiola J, et al. Dietary patterns and semen quality in young men. Hum

Reprod. 2012;27:2899–2907.

6. Lioret S, McNaughton SA, Crawford D, et al. Parents’ dietary patterns are significantly correlated:

findings from the Melbourne Infant Feeding Activity and Nutrition Trial Program. Brit J Nutr.

2012;108:518–526.

7. Mendiola J, Torres-Cantero AM, Moreno-Grau JM, et al. Food intake and its relationship with

semen quality: a case-control study. Fertil Steril. 2009;91: 812–818.

8. Afeiche MC, Gaskins AJ, Williams PL, et al. Processed meat intake is unfavorably and fish intake

favorably associated with semen quality indicators among men attending a fertility clinic. J Nutr.

2014;144:1091–1098.

9. Esmaeili V, Shahverdi AH, Moghadasian MH, et al. Dietary fatty acids affect semen quality: a

review. Andrology. 2015;3:450–461.

10. Cutillas-Tolín A, Mínguez-Alarcón L, Mendiola J, López-Espín JJ, Jørgensen N, Navarrete-Muñoz EM,

Torres-Cantero AM, Chavarro JE. Mediterranean and western dietary patterns are related to

markers of testicular function among healthy men. Hum Reprod. 2015;30:2945-55.

http://www.ncbi.nlm.nih.gov/pubmed/26721685









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11. Liu CY, Chou YC, Chao JC, Hsu CY, Cha TL, Tsao CW. The Association between Dietary Patterns and

Semen Quality in a General Asian Population of 7282 Males. PLoS One. 2015;28;10(7):

12. Chiu YH, Afeiche MC, Gaskins AJ, Williams PL, Petrozza JC, Tanrikut C, Hauser R, Chavarro JE. Fruit

and vegetable intake and their pesticide residues in relation to semen quality among men from a

fertility clinic. Hum Reprod. 2015;30:1342-51.

Intended audience:

Urologists, Andrologists, Male infertility specialists

Deadline:

July 26, 2016







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Sajal Gupta, MD, TS (ABB) Assistant Professor, Lerner College of Medicine

Supervisor, Andrology Center Assistant Research Coordinator, Center for Reproductive Medicine

Cleveland Clinic Email: [email protected]

Mobile: (216) 312-0826

2. IMPACT OF DRUGS ON OOCYTE QUALITY

Background:

The female reproductive function is directly determined by the ovarian life span. Ovary is a metabolically

active organ and serves as a germ cell reservoir during reproductive life span of female. Ovary has

approximately 0.3 million primordial follicles that contain diplotene arrested oocytes. Pituitary

gonadotropins surge induces steroidogenesis, follicular growth, development, maturation and ovulation

in most of the mammalian species. Environmental changes, lifestyle changes, pathological conditions or

drugs treatment may induce accumulation of ROS leading to OS that may have a negative impact on

oocyte physiology by inducing apoptosis.

Significance:

Reproductive aging is an increasingly pressing problem facing women in modern society, due to delay in

child bearing. The postponement of childbearing, which is a demographic trend in all several countries,

contributes considerably to the increasing proportion of subfertile couples that require assisted

reproductive technology (ART) procedures. Indeed, age of the female partner is one of the most significant

factors influencing the clinical outcomes of ART cycles. Our review examines the enzymatic antioxidants

such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione oxidase and

non-enzymatic antioxidants such

as vitamin C, taurine, hypotaurine, vitamin E, Zn, selenium (Se), betacarotene, and carotene and their

beneficial effects on oocyte quality. Oocyte post-ovualtory aging can be overcome by the peri-ovulatory

putrescine supplementation which is being investigated as e new intervention. It could act as a possible

remedy for reproductive aging. Review also examines the role of calcium channel blockers and anticancer

drugs on oocyte quality. This review is significant in reviewing the literature on current interventions to

improve overall oocyte quality in women.

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Outline:

1. Changes in oocyte quality with reproductive ageing structural changes and underlying

mechanisms

2. Impact of Oxidative stress on oocyte quality

3. Antioxidants; N-Acetyl-Cysteine and l-Carnitine do they have protective effects on oocyte

4. Interventions to improve oocyte maturation in older women by overcoming including Loss of

chromosome cohesion, mitochondrial dysfunction, defective spindles and insufficient histone

deacetylation

5. Periovulatory drug interventions for enhancing oocyte quality

6. Calcium channel blockers: do they prevent premature oocyte ageing

7. Anticancer drugs and their impact on oocytes

8. Conclusions and future research

Literature review:


exhaustive literature review needs to be done before the article

Journal:

To be decided.

Suggested Reading:

Resources of Cleveland Clinic Alumni Library

1. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-

obese women undergoing in vitro fertilization: a pilot study. Rago R, Marcucci I, Leto G,

Caponecchia L, Salacone P, Bonanni P, Fiori C, Sorrenti G, Sebastianelli A. J Biol Regul Homeost

Agents. 2015 Oct-Dec;29(4):913-23.

2. Peroxynitrite deteriorates oocyte quality through disassembly of microtubule organizing centers.

Khan SN, Shaeib F, Thakur M, Jeelani R, Awonuga AO, Goud PT, Abu-Soud HM. Free Radic Biol

Med. 2016 Feb;91:275-80. doi: 10.1016/j.freeradbiomed.2015.12.033. Epub 2015 Dec 31.





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3. Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-

related infertility. Da Broi MG, Navarro PA. Cell Tissue Res. 2016 Apr;364(1):1-7. doi:

10.1007/s00441-015-2339-9. Epub 2015 Dec 19. Review.

4. Developmental competence of immature oocytes aspirated from antral follicles in patients with

gynecological diseases. Safian F, Khalili MA, Karimi-Zarchi M, Mohsenzadeh M, Ashourzadeh S,

Omidi M. Iran J Reprod Med. 2015 Aug;13(8):507-12.

5. The Defensive Role of Cumulus Cells Against Reactive Oxygen Species Insult in Metaphase II

Mouse Oocytes. Shaeib F, Khan SN, Ali I, Thakur M, Saed MG, Dai J, Awonuga AO, Banerjee J, Abu-

Soud HM. Reprod Sci. 2016 Apr;23(4):498-507. doi: 10.1177/1933719115607993. Epub 2015 Oct

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6. Follicular fluid levels of vascular endothelial growth factor and its receptors and pregnancy

outcome of women participating in intracytoplasmic sperm injection cycles. Ntala V,

Asimakopoulos B, Veletza S, Alexandris E, Karachaiou V, Nikolettos N. Clin Exp Obstet Gynecol.

2015;42(4):437-41.

7. N-Acetyl-Cysteine and l-Carnitine Prevent Meiotic Oocyte Damage Induced by Follicular Fluid

From Infertile Women With Mild Endometriosis. Giorgi VS, Da Broi MG, Paz CC, Ferriani RA,

Navarro PA. Reprod Sci. 2016 Mar;23(3):342-51. doi: 10.1177/1933719115602772. Epub 2015

Sep 3.

8. Targeting oocyte maturation to improve fertility in older women. Liu XJ. Cell Tissue Res. 2016

Jan;363(1):57-68. doi: 10.1007/s00441-015-2264-y. Epub 2015 Sep 2.

9. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a

Potent Activator of Granulosa Cells and Improves Oocyte Quality. Mottershead DG, Sugimura S,

Al-Musawi SL, Li JJ, Richani D, White MA, Martin GA, Trotta AP, Ritter LJ, Shi J, Mueller TD, Harrison

CA, Gilchrist RB.

10. Arginine methyltransferases mediate an epigenetic ovarian response to endometriosis. Baumann

C, Olson M, Wang K, Fazleabas A, De La Fuente R. Reproduction. 2015 Oct; 150(4): 297-310. doi:

10.1530/REP-15-0212. Epub 2015 Jul29.Fertil Steril. 2016 Mar; 105(3): 548-59.

11. Aging and the environment affect gamete and embryo potential: can we intervene? Meldrum DR,

Casper RF, Diez-Juan A, Simon C, Domar AD, Frydman R.
















http://www.ncbi.nlm.nih.gov/pubmed/?term=Meldrum%20DR%5BAuthor%5D&cauthor=true&cauthor_uid=26812244

http://www.ncbi.nlm.nih.gov/pubmed/?term=Casper%20RF%5BAuthor%5D&cauthor=true&cauthor_uid=26812244

http://www.ncbi.nlm.nih.gov/pubmed/?term=Diez-Juan%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26812244

http://www.ncbi.nlm.nih.gov/pubmed/?term=Simon%20C%5BAuthor%5D&cauthor=true&cauthor_uid=26812244

http://www.ncbi.nlm.nih.gov/pubmed/?term=Domar%20AD%5BAuthor%5D&cauthor=true&cauthor_uid=26812244

http://www.ncbi.nlm.nih.gov/pubmed/?term=Frydman%20R%5BAuthor%5D&cauthor=true&cauthor_uid=26812244


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Intended audience: reproductive endocrinologists, reproductive biologists and gynecologists

Deadline:

July 26, 2016


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Sezgin Ozgur Gunes, PhD Associate Professor, Ondokuz Mayis University,

Department of Medical Biology Samsun, Turkey

Email: [email protected]

3. DEFECTS OF MICROTUBULES ASSOCIATED WITH MALE INFERTILITY

Background:

Microtubules are tubulin polymers that have function many essential cellular processes including cell

division and migration. In addition, they have roles in sperm head shaping, and sperm motility. Several

defects of the different parts of that compose the microtubules have been described and associated to

human male infertility.

Significance:

Microtubules are associated dynamic changes in cytoskeleton, organelle movement, mitosis, meiosis and

motility during spermatogenesis.

Outline:

1. Background

2. Methods

3. Structure and functions of microtubules

4. Microtubule dynamics

5. Microtubules in Sertoli cells

6. Flagellum formation

7. Conclusions

Literature review:

Preliminary literature searches have been done using resources of Cleveland Clinic Alumni Library. An

exhaustive literature review needs to be done before the article is written.

Journal:

[email protected]


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Review article. Journal to be decided.

Suggested readings:

1. O'Donnell L, O'Bryan MK. Microtubules and spermatogenesis. Semin Cell Dev Biol. 2014

Jun;30:45-54.

2. Terada Y, Schatten G, Hasegawa H, Yaegashi N. Essential roles of the sperm centrosome in human

fertilization: developing the therapy for fertilization failure due to sperm centrosomal

dysfunction. Tohoku J Exp Med. 2010 Apr;220(4):247-58.

3. Terada Y.Human sperm centrosomal function during fertilization, a novel assessment

for male sterility.Hum Cell. 2004 Dec;17(4):181-6.

4. Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner DJ, Okuda H, Whittle B, Jans

DA, Efthymiadis A, McLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O'Bryan MK. LRGUK-1 is

required for basal body and manchette function during spermatogenesis and male fertility.

5. PLoS Genet. 2015 Mar 17;11(3):e1005090

6. Mitchell V, Sigala J, Ballot C, Jumeau F, Barbotin AL, Duhamel A, Rives N, Rigot JM, Escalier D, Peers

MC. Light microscopy morphological characteristics of the sperm flagellum may be related to

axonemal abnormalities. Andrologia. 2015 Mar;47(2):214-20

7. Ben Khelifa M, Coutton C, Zouari R, Karaouzène T, Rendu J, Bidart M, Yassine S, Pierre V, Delaroche

J, Hennebicq S, Grunwald D, Escalier D, Pernet-Gallay K, Jouk PS, Thierry-Mieg N, Touré A, Arnoult

C, Ray PF. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male

infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet. 2014

Jan 2;94(1):95-104.

8. Kuo PL, Chiang HS, Wang YY, Kuo YC, Chen MF, Yu IS, Teng YN, Lin SW, Lin YH.

9. SEPT12-microtubule complexes are required for sperm head and tail formation. Int J Mol Sci. 2013 Nov 7;14(11):22102-16

Intended audience:

Andrologist, gynecologists, reproductive endocrinologists, embryologists and basic scientists

Deadline:

July 26, 2016













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Kothandaraman Narasimhan, PhD American Center and Center for Reproductive Medicine

Cleveland Clinic E-mail: [email protected]

Mobile: (216) 482-5577

4. IMPACT OF ENDOCRINE DISRUPTING COMPOUNDS ON CAUSING MALE INFERTILITY

Background:

Humans are exposed on a daily basis to a wide array of toxic compounds that interfere with vital

functioning of our various biological systems. Endocrine disrupting compounds or commonly called as EDs

as well as androgen disruptors play a major role in the malfunctioning of male reproductive system

subsequently affecting the male fertility. Extensive work has been carried out on animal model systems

on the exposure to these organic compounds. These works were complimented with cell line studies to

study the specific effects these metabolites on pathways associated with male reproductive system. The

primary targets of EDs as well as androgen disruptors molecules including organochlorinated pesticides,

industrial chemicals, and plasticizers with capacity to ligand the androgen receptor are the genes and

proteins involved in the reproductive pathways centered around the androgen receptor since it is the key

molecule that regulates the major events associated with spermatogenesis. The effect of these

compounds have a major impact on the normal male developmental programming during spermiogenesis

as well as subsequent events for the processing of the fully functional spermatozoa. The maximum impact

of these accumulated compounds is observed in the microenvironment environment of the developing

immature as well as the mature spermatozoa. The deleterious effects of these compounds are manifested

in the form of low sperm counts, malignancies associated with the prostate, as well as testicular

dysgenesis syndrome as proved by animal model studies. This review will highlight the evidence for

androgen and ED disrupting chemicals that act through interference with the specific receptors that

perturbs the normal functioning of the male reproductive system leading to male infertility.

Significance:

The current study will help to summarize the latest development on the role of endocrine disrupting

compounds in affecting male infertility. Toxic compounds, pesticides and EDCs and their effect on

spermatogenesis as well as malfunctioning of the male reproductive system will be targeted in the

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proposed assignment. This study will help to understand the close association between the various EDCs,

which we come in contact, and their effect on the fecundity factor of males in the long run.

Outline:

1. Introduction

2. Prevalence of EDs in the environment

3. Classes of EDs associated with male reproductive function

4. Role of EDs/androgen disruptors in male reproduction

5. Primary targets and localization if EDs in male reproductive system

6. Mechanism of action EDs in the malfunctioning of the male reproductive system

7. Invitro and invivo studies related to EDs and fertility

8. Genetic regulation of EDs in mimicking endocrine function associated with male infertility

9. TOXICO genomics and proteomics studies associated with EDs and male infertility

10. Case studies associated with ED related to male infertility

Literature review:


exhaustive literature review needs to be done before the article is prepared.

Journal:

Will be decided later.

Suggested reading:

1. Rengaraj, D., W.S. Kwon, and M.G. Pang, Effects of motor vehicle exhaust on male reproductive

function and associated proteins. J Proteome Res, 2015. 14(1): p. 22-37.

2. Mersha, M.D., et al., Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults. Behav Brain Funct, 2015. 11: p. 27.

3. Kumar, N., S. Srivastava, and P. Roy, Impact of low molecular weight phthalates in inducing reproductive malfunctions in male mice: Special emphasis on Sertoli cell functions. Gen Comp Endocrinol, 2015. 215: p. 36-50.


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4. Menezo, Y., et al., Effect of antioxidants on sperm genetic damage. Adv Exp Med Biol, 2014. 791: p. 173-89.

5. Kranvogl, R., et al., Simultaneous determination of phthalates, their metabolites, alkylphenols and bisphenol A using GC-MS in urine of men with fertility problems. Acta Chim Slov, 2014. 61(1): p. 110-20.

6. Knez, J., Endocrine-disrupting chemicals and male reproductive health. Reprod Biomed Online, 2013. 26(5): p. 440-8.

7. Bonde, J.P., Occupational causes of male infertility. Curr Opin Endocrinol Diabetes Obes, 2013. 20(3): p. 234-9.

8. Gaertner, K., et al., Identification and expression of the ecdysone receptor in the harpacticoid copepod, Amphiascus tenuiremis, in response to fipronil. Ecotoxicol Environ Saf, 2012. 76(2): p. 39-45.

9. Luccio-Camelo, D.C. and G.S. Prins, Disruption of androgen receptor signaling in males by environmental chemicals. J Steroid Biochem Mol Biol, 2011. 127(1-2): p. 74-82.

10. Balabanic, D., M. Rupnik, and A.K. Klemencic, Negative impact of endocrine-disrupting compounds on human reproductive health. Reprod Fertil Dev, 2011. 23(3): p. 403-16.

11. Eertmans, F., et al., Endocrine disruptors: effects on male fertility and screening tools for their assessment. Toxicol In Vitro, 2003. 17(5-6): p. 515-24.

12. Petrelli, G. and A. Mantovani, Environmental risk factors and male fertility and reproduction. Contraception, 2002. 65(4): p. 297-300.

Intended audience:

Andrologists, male infertility specialists, urologists and basic biologists

Deadline:

July 26, 2016


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Gulfam Ahmad, PhD, MCE, MRD, DIU Department of Physiology

University of Health Sciences, Lahore Pakistan

[email protected] Mobile: +966 502807016

5. Phthalates, semen quality and male fertility: an evidence based review

Background

Phthalates are esters of phthalic acid and a class of organic chemicals used as plasticizer to increase the

flexibility of polyvinylchloride (PVC). These are used in large variety of products such as food packaging,

medical devices, medications, toys as well as cosmetics and personal care products (Crinnion, 2010). They

are also commonly used in various mediums to maintain the color and scent (Cadogan and Howick, 1996)

in perfumes, lotion, nail polish, lipsticks and deodorants (Blounet et al., 2000). Among the primary

phthalate compounds diethyl-hexyl phthalate (DEHP) is most commonly used plasticizer worldwide (Lorz

et al., 2003). Other important phthalates products are dibutyl phthalate (DBP), diethyl phthalate (DEP),

butylbenzyl phthalate (BBzP), and di-iso and n-butyl phthalate (DiBP, DnBP) (Koch et al., 2003). In the

body, phthalates are rapidly metabolized to their respective monoesters (Silva et al., 2006). They undergo

a series of phases i.e. phase I hydrolysis and phase II conjugation reactions and are then excreted in feces

and urine (Frederiksen et al., 2007). Both primary and secondary metabolites are biologically active

(Forster et al., 1981; Gray et al., 1986; Richburg et al., 1996; Stroheker et al., 2005). Phthalates have

negative impact on male fertility. The New York Times report (March 21, 2014 1:31 PM). “To study the

impact of everyday chemicals on fertility, federal researchers recently spent four years tracking 501

couples as they tried to have children. One of the findings stood out: while both men and women were

exposed to known toxic chemicals, men seemed much more likely to suffer fertility problems as a result”.

The impact of phthalates starts at testicular level as the hormonal environment is essential for the

developing male gonads and male reproductive tract. In utero as well as in adults phthalates exposure

can interfere with the production or action of hormones which may partially or completely prevent the

masculinization process of the developing fetus and could also compromise the semen quality leading to

fertility issue. The adverse effects of phthalates on male development and reproduction might be

mediated from reactive oxygen species (ROS), that have been shown to induce DNA damage and may

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accelerate the process of germ cell apoptosis, leading to the decline in sperm counts associated with male

infertility. This association seems conceivable, since (i) phthalates have been reported to cause

peroxisome proliferation, a process also featured by an enhanced production of ROS (ii) ROS mediated

female fertility disorders share many pathogenic similarities with the ones on the male.

Significance

This article will review the data published on semen characteristics in response to the exposure to

phthalates and will contribute in the understanding of the role of phthalates in male fertility.

Outline

1. Phthalates as endocrine disrupting chemicals

2. Chemistry of the phthalates metabolites

3. Role of phthalates in testes development

4. Role of phthalates in development of male reproductive tract

5. Phthalates and neonatal exposure

6. Phthalates and semen characteristics

7. Phthalates and male infertility

8. Conclusions

9. Recommendations

Literature review:

Preliminary literature search has been done using Google Scholar, PubMed and the keyword search. An

exhaustive literature review needs to be done before the article is prepared.

Journal:

Will be decided later.

Suggested readings


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1. D.K. Agarwal, S. Eustin, J.C. Lamb, J.R. Reel, W.M. Kluwe. Effects of DEHP on the gonadal

pathophysiology, sperm morphology and reproductive performance in male rats. Envir. Health

Perspect., 65 (1986), pp. 653–659.

2. A. Agarwal, R.A. Saleh, M.A. Bedaiwy. Role of reactive oxygen species in the pathophysiology of

human reproduction. Fertil. Steril., 79 (2003), pp. 829–843.

3. N.J. Barlow, S.L. Phillips, D.G. Wallace, M. Sar, K.W. Gaido, P.M. Foster. Quantitative changes in

gene expression in fetal rat testes following exposure to di(n-butyl) phthalate. Toxicol. Sci., 73

4. (2003), pp. 431–441.

5. C.J. Bowman, N.J. Barlow, K.J. Turner, D.G. Wallace, P.M. Foster. Effects of in utero exposure to

finasteride on androgen-dependent reproductive development in the male rat. Toxicol. Sci., 74

(2003), pp. 393–406

6. Buck Louis GM, Sundaram R, Sweeney AM, Schisterman EF, Maisog J, Kannan K. Urinary bisphenol

A, phthalates, and couple fecundity: the Longitudinal Investigation of Fertility and the

Environment (LIFE) Study. Fertil Steril. 2014 May;101(5):1359-66.

7. N. Bhattacharya, J.M. Dufour, M.N. Vo, J. Okita, R. Okita, K.H. Kim. Differential effects of

phthalates on the testis and the liver. Biol. Reprod., 72 (2005), pp. 745–754.

8. E. Carlsen, A. Giwercman, N. Keiding, N.E. Skakkebaek. Evidence for decreasing quality of semen

during past 50 years. Bmj, 305 (1992), pp. 609–613

9. J.C. Corton, P.J. Lapinskas. Peroxisome proliferator-activated receptors: mediators of phthalate

ester-induced effects in the male reproductive tract? Toxicol Sci. 2005 Jan;83(1):4-17.

10. S.M. Duty, M.J. Silva, D.B. Barr, J.W. Brock, L. Ryan, Z. Chen, R.F. Herrick, D.C. Christiani, R. Hauser.

Phthalate exposure and human semen parameters. Epidemiology, 14 (2003), pp. 269–277.

Intended Audience

This review is of interest to the fertility specialists, reproductive biologists and toxicologists, andrologists.

Deadline:

July 26, 2016

Documents

SCIENTIFIC WRITING PROJECT...Synopsis of Writing Project 5 73. Scientific Writing Projects 2016 Summer Internship 11. Liu CY, Chou YC, Chao JC, Hsu CY, Cha TL, Tsao CW. The Association