Environmental Impacts on Reproductive Health

ISSN 2395-2806

Issue 18 | February, 2016

Environmental Impacts on Reproductive Health

Editor-in-Chief: Prof. N. K. Lohiya Editors: Dr. P. K. Mishra, Dr. R. S. Sharma & Dr. Sunil Kumar

Indian Society for the Study of Reproduction and Fertility ISSRF Executive President Dr. N. K. Lohiya, Jaipur Vice-Presidents Dr. Suneeta Mittal, New Delhi Dr. Sudha Salhan, New Delhi Secretary Dr. R. S. Sharma, New Delhi Joint Secretary Dr. A. H. Bandivadekar, Mumbai Treasurer Dr. A. S. Ansari, Jaipur Members Dr. Nomita Chandhiok, New Delhi Dr. S. G. Dastidar, Kolkata Dr. Sujata Kar, Bhubaneswar Dr. S. S. Majumdar, New Delhi Dr. P. B. Seshagiri, Bangalore Dr. G. Taru Sharma, Bareilly Dr. Dheer Singh, Karnal Co-Opted Members Dr. M. M. Misro, New Delhi Dr. Roya Rozati, Hyderabad Ex-Officio Members Immediate Past President Dr. C. P. Puri, Mumbai

Immediate Past Secretary Dr. Smita Mahale, Mumbai

ISSRF SECRETARIAT Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur - 302 004, INDIA Telephone No.: +91-141-2701809 • Fax No.: +91-141-2701809 E-mail: [email protected] • Website: www.issrf.org Cover Design : Dr. Rupesh K. Srivastava with inputs of Mr. Deepak Jaiswal

Environmental Impacts on Reproductive Health ISSRF

ñdmñÏ` Ed§ n[adma H$ë`mU _§Ìr ^maV gaH$ma Minister of Health & Family Welfare Government of India

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OJV àH$me ZS²>S>m Jagat Prakash Nadda

Message Climate change presents a global public health challenge. Disruptions of physical, biological and ecological systems might have serious health impacts predicted to manifest in many ways that include rapid growth in non-communicable diseases; changes in the prevalence and geographical distribution of food- and waterborne illnesses and other infectious diseases; and threats to reproductive health. Environmental sustainable links to sexual and reproductive health is not new but it has regained momentum within discussions about how to tackle the causes and consequences of climate change. I am sure that release of the 18th Issue of ISSRF Newsletter on “Environmental Impacts on Reproductive Health” during International Conference on Reproductive Health with Emphasis on Occupational, Environmental and Lifestyle Factors & 26th Annual Meeting of the ISSRF at Ahmedabad on February 18, 2016 will be a grand success. I wish ISSRF all the best for its future academic endeavours.

(Jagat Prakash Nadda)

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Message

Dr. Soumya Swaminathan, MD, FASc, FNASc, FAMS Secretary - Department of Health Research & Director General, Indian Council of Medical Research, New Delhi

Public health problems resulting from exposure to biologically contaminated water; inadequate sanitation; indoor smoke; poor food supply; and unsafe use of chemicals and waste disposal, rank among the highest environmental burden of disease worldwide. Promotion of collaborative research among clinicians and scientists in developing and developed countries is critical to addressing health problems in their national contexts. Besides capacity building, such kind of studies might be helpful to implement prevention/intervention and remediation strategies and put in place evidence-based public health policies at the country level. The publication of ISSRF Newsletter (18th edition) on the theme “Environmental Impacts on Reproductive Health” is very well timed when we are debating on issues related to sustainable development, climate change, reducing carbon foot-print and environment and energy access and security. I am hopeful that this publication will be beneficial for scientists, public health executives, program managers and clinicians from the field of reproductive health sciences and medicine. I take this opportunity to convey my best wishes for all success to ISSRF to strengthen its scientific endeavours according to changing realities and needs!

(Soumya Swaminathan) Message

Dr. V. M. Katoch MD, FNASc, FASc, FAMS, FNA Former Secretary, Department of Health Research, Govt. of India and Director General, Indian Council of Medical Research, New Delhi

I am happy to know that the Indian Society for the Study of Reproduction and Fertility (ISSRF) is bringing out the 18th edition of its newsletter dedicated to ‘Environmental Impacts on Reproductive Health’ which will be released during 26th Annual Meeting of ISSRF along with International Conference on Reproductive Health with Emphasis on Occupational, Environmental & Lifestyle Factors (ISSRF-2016) at National Institute of Occupational Health - NIOH (ICMR), Ahmedabad, February 18-20, 2015. Environment has several physical, chemical, biological and social components which have impact on not only human reproductive health but also those of live-stock and other living species. This fact helps us to develop models for improving human reproductive health. Further during the recent years many man made environmental changes mainly due to chemicals, have been feared to have relationships with our endocrine systems thus indirectly thought to have impact on metabolism and reproductive health. It is right time that we start looking at scientific evidences so that life style and policy changes could be recommended with confidence. I am optimistic that publication of this special issue of ISSRF Newsletter and its release at the next conference at Ahmedabad will be another important contribution of ISSRF to Indian people. NIOH (ICMR) is an important national institution focused on occupational & environmental health and is thus a suitable venue for such deliberations. I take this opportunity to convey my best wishes for the success of this important national meeting and international conference.

(V. M. Katoch) 2

ISSRF Newsletter v Issue 18 v February, 2016 ISSRF

List of Contributors From the Desk of the Editor-in-Chief N. K. Lohiya

Is High Salt Intake Making us Infertile are Th17 Cells to Blame ? Rupesh Kumar Srivastava 28

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Environmental Impact on Reproductive Health - Can Biomarkers Offer any Help ? Pradyumna Kumar Mishra 7

An in-vitro System to Assess Teratogenicity of Drugs/Environmental Toxicants Gyanendra Singh and Neeraj Sinha 31

Sanitation, Menstrual Hygiene, and the Social Environment: Seriously Neglected Aspects in the Life Course of Indian Women Bijaya K. Padhi and Pinaki Panigrahi 8

Fluoride Reproductive Toxicity and its Mitigation M. V. Rao

Heat Stress Impairs Follicular DynamicsStrategies for its Management Vikash Chandra and G. Taru Sharma 9

Globalization, Anthropogenic Environmental Change on Human Health and Reproducibility Amlan Kanti Ray and Pramathes Das Mahapatra 36

Environmental Factors and Reproductive Health Krishna Kant, Anil Kumar Tomar and Savita Yadav 11

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In Utero Exposure To Bisphenol - A (BPA) And Its Translational Impacts On Adult Female Reproductive Health - A Narrative Review Christy Lite, Melita Juliet J. and Winkins Santosh 39

Microwave Radiations Exposure Effects on Reproductive System of Male Rats J. Behari 13

Role of Y-chromosomal & Mitochondrial Genes in Male Infertility Asoke Kumar Pal and Prafulla S. Ambulkar 42

Declining Sperm Count and Quality: Can we Rescue? Kiran Singh 15

Health Hazards of Dioxins Ramya Nair, Winkins Santosh and S. Barathi

Polybrominated Diphenyl Ethers: Effect on Male Reproductive Health as Thyroid Hormone Disruptors Debarshi Sarkar and Shio Kumar Singh 19

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Effects of Polychlorinated Biphenyls and Phthalates on Male Reproductive System in Adult and F1 Male Offspring Rats - A Review Arunakaran Jagadeesan 47

Dose Response Relationship Between Radio Frequency Electromagnetic Field and Male Fertility Pattern Kavindra Kumar Kesari 23

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Infrared Radiation : Radiotoxic or Radiohormetic Impact on Male Reproductive Tissues? Hyacinth Highland

Breast Cancer Profile in India and Environmental Risk Factor Anupam Basu

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52 Mobile Phones and Wi-Fi: Looming Threat to Male Reproductive Health Sutapa Mukherjee 73

Lead and Male Reproduction: Impact of Workplace Exposure Nibedita Naha 54

Stress and Egg Quality Shilpa Prasad, Meenakshi Tiwari, Ashutosh N. Pandey, Anima Tripathi, Amritanjali Pandey, Tulsidas G. Shrivastav and Shail K. Chaube 76

Vulnerability of Alcohol - Women Pays More Tolls at Gut Liver Highway ? Subhrajit Biswas 61 Insulin Regulation of Ovarian Function: Lessons from Zebrafish (Danio rerio) Eggs Debabrata Das and Sudipta Maitra 64

Environmental Toxicants and Reproductive Health - an Environmental Perspective Radhey Shyam Sharma, Swagata Karmakar and Vandana Mishra 78

Climate Change Related Multiple Environmental Stressors Impacts on Livestock Reproductive Health and its Amelioration V. Sejian, V.P. Maurya, D. Kumar, G. Taru Sharma and S.M.K. Naqvi 66

Effect of Methyl Parathion on Reproductive Health Guruprasad Kalthur, Ramya Nair and Satish Kumar Adiga

Environmental Toxicants Exert Hazardous Effect on Male Reproduction Anand Katiyar, Poonam Singh and Srikanta Kumar Rath 70

Polycystic Ovary Syndrome: Is it a Consequence of Endocrine Disruption by BPA? Rita Singh, Priya Bhardwaj and Shikha Sagar 85

Valuable comments of the readers will serve as the source of inspiration and also help us to improve upon future newsletters of the Society 4

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From the Desk of the Editor-in-Chief

Prof. N. K. Lohiya, FNASc, FAMS, FIAES, FEMSI President-Indian Society for the Study of Reproduction and Fertility (ISSRF) & Emeritus Medical Scientist, University of Rajasthan, Jaipur On 25 September 2015 at the United Nations Sustainable Development Summit in New York, more than 173 heads of government adopted the historic 2030 Agenda for Sustainable Development. This new Agenda is built around 17 interconnected Sustainable Development Goals (SDGs) which aims to chart a course for eradicating poverty, fight inequality and injustice, and tackle climate change by 2030. Well, the success of this massive political declaration will purely depend on how countries adopt, adapt to and commit to these global goals. Therefore, a global monitoring framework will have to measure the progress towards SDGs taking help of a set of key indicators. For uniform global action-oriented implementation, national policies and priorities that account for different national realities, capacities and levels of development should be taken into consideration integrating economic, social and environmental aspects and their inter-linkages. Sexual and reproductive health and rights are appropriately placed at sustainable development goal (SDG) goal 3 (ensure healthy lives and promote well-being for all at all ages); and SDG goal 5 (achieve gender equality and empower all women and girls). Whereas, target 3.8 (SDG 3), enunciates universal accesses to sexual and reproductive health for all, target 5.9 (SDG 5) articulates that universal access to sexual health and reproductive health rights (SRHR) is fundamental to guarantee sustainable development. The SDGs follow and expand on the millennium development goals (MDGs) and India’s achievement in respect of the health related MDGs was reticent. Barring one of the four health related MDGs, we missed the targets on important parameters like reducing infant mortality, improving maternal health and curb the spread of communicable diseases. Due to a combination of excellent institutional measures, their proper implementation, awareness programmes and increased participation of the states, we were right on track to halt and reversal of HIV/AIDs. Although our effort had been exemplary but inability to achieve the MDGs, provides much scope for improvement. True realization of the SDGs will be fruitful only when decentralization of planning and implementation of reproductive health programmes is coupled with a nuanced outlook towards removal of socio-economic barriers. Global funding on research and development and innovation will be central to achieve these goals, and in particular the SRHR which has been largely overlooked by the SDG indicator development process. We need to understand that substantial burden of poverty-related and neglected issues associated with reproductive health and disease conditions falls overwhelmingly on low- and middle-income countries. Besides improving our understanding of how to best target the tools we already have, new and improved drugs; vaccines; diagnostics; and other critical innovations will be fundamental towards securing the future of risks related to effective implementation of SRHR which has been largely ignored in the post-2015 development agenda. Especially, for a country such as India, there is an urgent need for public health and philanthropic funding to assist monitor investments in, and use of, research to promote health, equity, and development for achieving the SDGs. Despite having better scientific research institutions in our country, research and development and innovation capabilities mark significantly lower if compared with other four major emerging national economies: Brazil, Russia, China and South Africa. Although we are ahead of other peers when it comes to market knowledge, technology and creativity, but we rank poorly when compared to other metrics such as institutional support, human resources, research infrastructure and business sophistication in health sector. India accounts for 17 per cent of the global population and bear 20 per cent global health burden, but our health expenditure stands at approximately 1.2 per cent of its trillion dollar gross domestic products. Our policy-makers must comprehend that issues pertaining to reproductive health are inextricably linked to societal scenarios, and seek to target strengthening healthcare infrastructure, increasing spending which is still dismal for India, developing more incentives to join reproductive health services as well as evolve strategies to serve society on regionspecific issues. Reaching out to the marginalized poor and inaccessible should be fostered by collaborating with NGOs, academia and pharmaceutical companies. There is mounting evidence that environmental impact will have disastrous consequences for people and the planet. Increasingly erratic weather patterns, rising sea levels and extreme events such as cyclones, floods, droughts, desertification, pollution, and heat waves that may be attributed to human activity and the greenhouse gas emissions that 5


have triggered global warming will exacerbate already precarious developmental concerns, and could potentially affect progress on the SDGs. If swift action is not taken to mitigate this human impact, human rights will be adversely affected. Jeopardisation of fundamental requirements in availability of clean air, safe drinking water, adequate sanitation and sufficient food will have profound ramification on universal access to SRHR which is the key for the new developmental era. For effective monitoring of environmental impact on reproductive health-related matters, novel indicators should be integrated into mitigation and adaptation programmes to identify where “explicit vulnerabilities lie, and where prospects for mitigating and adapting can be found”. Climate change per se will have far reaching impacts on biology of reproduction. Many of these changes will negatively influence the fitness, survival and reproductive success of individuals. Therefore, there is an urgent need to recognise and underscore the inter-linkages between climate change and SRHR through supporting research that will evaluate the ill consequences of under-nutrition; lack of access to food; frequent heat waves and fires; more variable rainfall patterns; rising sea levels; and increased risks of flooding; on human reproductive health. We must realize that the reproductive health impact of climate change is expected to affect poorer populations disproportionally. Thankfully recently at Paris, during the UN climate change negotiations COP21 for health, a historic agreement was signed on Saturday 12 December 2015 by Heads of State, Parliamentarians and Civil Society to combat climate change, vital to both protecting and promoting human health. In my opinion, this will also prove to be a defining step towards protecting human reproductive health from severe, pervasive and irreversible environmental damage. Exogenous and endogenous factors that impact reproductive health involve a large number of distinct topics that include molecular toxicology, disease aetiology, developmental origins of disease, genetics, epigenomic modifications, and molecular physiological processes. Therefore, the scope of this current edition of ISSRF newsletter is really vast. On behalf of the Editorial Board I am delighted to announce the publication of 18th edition of ISSRF Newsletter and thank all authors for their valuable contributions. The quality of content published underpins the success of our newsletter and we are committed to ensure editorial excellence as we grow. On behalf of the Executive Committee of ISSRF, I congratulate the Editors of this volume: Dr. Pradyumna Kumar Mishra, Scientist - E & Head, Department of Molecular Biology, National Institute for Research in Environmental Health (ICMR), Bhopal; Dr. Radhey Shyam Sharma, Scientist G & Head, Division of Reproductive Biology and Maternal Health, Indian Council of Medical Research, New Delhi; and Dr. Sunil Kumar, Scientist G & Director-in-Charge, National Institute of Occupational Health (ICMR), Ahmedabad for their outstanding job.

(N. K. Lohiya)

Compliments & Congratulations to Recipients of ISSRF-2016 Awards Labhsetwar Award

Dr. M. S. Chauhan, NDRI, Karnal Dr. Sunil Kumar, NIOH, Ahmedabad Dr. G. Taru Sharma, IVRI, Izatnagar Dr. Pradeep Kumar G, RGCB, Thiruvananthapuram Prof. Savita Yadav, AIIMS, New Delhi Dr. Suresh Yenugu, University of Hyderabad, Hyderabad Dr. Rajesh Kumar Jha, CSIR-CDRI, Lucknow Dr. Sumit Agarwal, NII, New Delhi Prof. Chandana Haldar, BHU, Varanasi Prof. N. K. Lohiya, UOR, Jaipur Dr. Deepali Sundrani, IRSHA, Pune Ms. Swati Prakash Ahir, NIRRH, Mumbai Dr. S. K. Gupta, NII, New Delhi Prof. Suneeta Mittal, FMRI, Gurgaon Prof. (Dr.) Anil Kumar Srivastava, NDRI, Karnal

Founder President Dr. T. C. Anand Kumar Memorial Oration Prof. G. P. Talwar Gold Medal for Middle Career Scientists Prof. G. P. Talwar Young Scientist Awards Prof. L. S. Ramaswami Memorial Oration Prof. N. R. Moudgal Memorial Oration Prof. N. R. Moudgal Young Scientist Awards The Lifetime Achievement Award

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Maximum help to build this conceptual framework has come from both in-vitro and animal studies. Based on cutting-edge technological assessments employed for better molecular understanding, most complex reproductive ailments that include menstrual irregularities, early or delayed puberty, infertility, sub-fertility, early pregnancy loss, foetal death, impaired foetal growth, low birth weight, premature birth, structural or functional birth defects, polycystic ovary syndrome, endometriosis, uterine fibroids, reproductive tract infections, sexually transmitted diseases, and reproductive tract cancers have all been shown to have both genetic and epigenetic component. Given that developmental basis is apparently linked to adult disease outcome, there is a greater need to change our focus from treating diseases after they are detected to prevention. Several thousands of environmental contaminants penetrate daily into our environment and exert various kinds of stress response on reproductive health. Because of diversities in chemical nature, dose- response relationship and factors associated with susceptibility and vulnerability, design of risk assessment strategy is challenging. It is very likely that low and relatively innocuous concentration of contaminants often produce deleterious reproductive health effects, which are hard to be predicted, because measurable outcomes are expressed only after prolonged exposure. When these incipient effects are expressed, it might be too late to take corrective actions or steps to reduce risk. Therefore, it is essential to develop biomarkers that convincingly reflect adverse exposure-response relationship. New biomarkers might offer vital clues for environmental-associated reproductive system diseases and thus facilitate (i) early diagnosis of a disease; (ii) recurrence or progression of a disease; (ii) identification of individuals for disease prevention; (iv) as a potential target for drugs; (v) as a marker for a drug response. In molecular terms, biomarker identification clearly refers to a subset of markers that might be discovered using genomics, epigenomics, transcriptomics, metabolomics, proteomics, or imaging signatures. Delineating the molecular signatures of environmental-associated reproductive illness requires comprehensive knowledge of the entire cascade of events from the release of an environmental contaminant through absorption, actions and damage within the body and the development of disease. Defining the extent and impact of exposure is a central element for understanding a complex disease form. While ascertaining the possible implication of any exogenous moiety, the precise amount that is available (internal dose) after it is absorbed via ingestion, inhalation, in-utero, and dermal routes is only physiologically relevant. Once inside the body, the entity is transformed and either stored or eliminated, traversing through various metabolic pathways. Therefore, before validating a biomarker associated with any kind of environmental exposure (acute/chronic/occupational), it is necessary to discern where in this chemico-biological process the measured index comes from - that is whether it is a biomarker of exposure, susceptibility or effect. A potential biomarker can facilitate better identification of

A Word from the Editor ENVIRONMENTAL IMPACT ON REPRODUCTIVE HEALTH - CAN BIOMARKERS OFFER ANY HELP ? Pradyumna Kumar Mishra National Institute for Research in Environmental Health Indian Council of Medical Research, Bhopal [email protected]

Environmental health is broadly defined as those aspects of human health determined by physical, chemical, biological and social factors in the environment and encompasses the assessment and control of those factors. Within this definition, it is likely that exogenous and endogenous environmental determinants are not only targeted towards preventing disease and creating healthsupportive surroundings, but that affects all forms and stages of human lives. As most humans develop in a predictable fashion, growing from a fertilized egg to foetus, newborn, toddler, child, adolescent, and adult, there is little doubt that environment is a powerful modifier of the human reproduction and development. Exposure to environmental contaminants during the most critical developmental times, such as pre-conception, preimplantation, the foetal period, and early childhood, can trigger functional loss and developmental changes through both genetic and epigenetic modifications, among other mechanisms. While identifying and characterizing the significant consequences of these associated factors on human reproduction and development, two defined cluster of population have been found to be the most affected: (i) susceptible and; (2) vulnerable populations. Whereas, “susceptibility” refers to inherent biological factors, “vulnerability” indicates to population at higher risk due to personal factors. Population with both susceptibility and vulnerability are together referred to as “sensitive” population. Of late, research towards understanding the defined impact of both exo- and/or endogenous environmental determinants on molecular programming has opened a new perspective on the developmental and early life origins of human disease. Now, there are published scientific indications showing that a person’s fertility may even be the result of what her great grandmother was exposed to while she was in-utero. Does this suggest what a woman may be exposed to during her pregnancy can affect the fertility of her children, grandchildren and great grandchildren? Yes, besides change in the DNA sequence, transmission of this altered programming due to exposures during development have been shown to involve epigenetic modifications or changes in gene function. But, whether is it pragmatic to follow large human cohorts for 60 long years to see if they develop diseases based on what they were exposed to before birth ? 7


obstetrics and gynecology defined an Indian woman as one “who micturates once a day, defecates once a week, menstruates once a month, and parturates (delivers a baby) once a year”. I still have goose bumps when I think of that statement. I am saddened today after conducting medical and socio-behavioral research in the Indian community over the last fifteen years. Saddened to see my colleagues and the society at large to have accepted this statement as part of life. As if we do not have any social or moral responsibility to change this. We are males, in a male chauvinist society. I want my female colleagues, the girls in middle and high school not to feel powerless, and rise up to the cause. Not to wait for someone else to take the leadership role to bring about a change. Not to wait for research results to change their lives. Yes, policy makers will need evidence to make prudent investments. But, when a human being is bleeding in front of you, you do not ask for the cause of bleeding, impact of stopped bleeding, and how big will be the impact - you first make sure that you do everything possible to stop the bleeding so that you save the life of the person and then think about the next steps. India is bleeding. Bleeding in many different ways when it comes to reproductive health of girls and women. We do not need doctors, scientists, or politicians to tell a woman what is good for her. She needs to raise her voice and we all who pretend to care for human suffering need to be with her. It is much worse than HIV/AIDS, malaria, diarrhea, under nutrition, obesity, and all the chronic diseases combined. It is the basic right of a woman, the minimal need to support her physiology that supports the maintenance of human race. Menstrual hygiene and management (MHM) is a major public health issue that is poorly addressed and has not received adequate attention in the reproductive health interventions in developing countries including India. Women and girls are particularly vulnerable to poor reproductive health outcomes as a result of multiple sociocultural and economic factors that limit them equal rights with men. Millions of women today have limited access to hygienic menstruation management, and are often forced to adopt a range of unhealthy behaviors [1]. Few recent studies suggest that sanitation and hygiene-related practices contribute to reproductive disease risks in women through complex biological, environmental, and social pathways [2–4]. The practice of good menstrual hygiene reduces the incidence of reproductive tract infection. Good hygienic practices, such as use of sanitary pads and adequate washing of the genital areas, are essential during menstruation period. Women and girls of reproductive age need access to clean and soft absorbent sanitary products which in the long run can protect their health from various infectious and inflammatory conditions. MHM practices vary from country to country and depend on a woman’s socioeconomic status, personal preferences, local traditions and cultural beliefs, and WASH access. MHM practices can be particularly unhygienic and inconvenient for girls and women in poorer settings. In India, 43% to 88% of girls wash and reuse cotton cloths rather than using disposable pads. Sanitization of reusable material is often difficult because

exposure, measure both susceptibility and vulnerability, and increase prediction of outcome. The scientific impact of development and validation of biomarkers in environmental-associated reproductive system diseases is highly significant as it opens the road to the exploitation, using modern-omics technologies, of thousands of biological matrices currently housed in existing bio-banks of several medical institutes. Understanding the intricate relationship between exoand/or endogenous environmental risks within populations, how environmental exposures affect human lives, and how this knowledge can be translated to reduce associated morbidities and enhance quality of life is precisely what, this newsletter aims to address. Recently, a large number of environmental and host risk factors have been identified that are associated with reproductive health risk resulting in dramatic fold increase in number of biomarkers reaching for clinical validation. However, translation of these for use in the population-level screening in such a way as to have a significant impact on clinical practice is still a major challenge. Often, the use of a predictive biomarker has poorer test characteristics when it is validated in two separate populations. If validated in a low disease prevalence setting, the predictive value may be low; on the other hand, in high disease prevalence setting, the same biomarker could have enough potential clinical utility. Therefore, the process of identification and validation for clinical application among the large number of purported biomarkers associated with environmental illness is a critical step in the translation process. Key to this process is to understand the differences between evaluating biomarkers and risk factors for prevention versus disease risk prediction and early detection. A robust indulgence in analysing these differences will be necessary to facilitate the translational process. The challenges are enormous but a cutting-edge tailored approach may help to set priorities for future reproductive health research, monitoring, and surveillance activities and for potential risk assessment or risk management follow-up efforts.

SANITATION, MENSTRUAL HYGIENE, AND THE SOCIAL ENVIRONMENT: SERIOUSLY NEGLECTED ASPECTS IN THE LIFE COURSE OF INDIAN WOMEN Bijaya K. Padhia and Pinaki Panigrahib* a

Center for Environmental and Occupational Health, Asian Institute of Public Health Bhubaneswar b

Center for Global Health and Development College of Public Health, University of Nebraska Medical Center, USA [email protected]

More than 35 years ago I was struck as a young man when my medical school professor in India in the department of 8


expansive studies are also needed to explore whether the impacts of poor MHM are perpetuated by birth outcome to affect offspring life trajectories. Policy makers can address these disparities by (a) Subsidizing the costs of sanitary napkins for economicallydeprived groups; (b) improving awareness of hygienic MHM practices through public and school-based education campaigns, including among boys and men; (c) investing in an adequate, well-maintained sanitation facilities with a water supply, particularly in the urban slums; and (d) providing separate, private toilets with a water supply for women in the work place and educational institutions. References

of poor availability of soap, clean water, and private washing and drying space. A limited body of evidence suggests that unhygienic MHM practices may increase a woman’s susceptibility to urogenital infections, such as BV, or UTIs [1, 3]. Many studies in the US and Europe have demonstrated that clinical history of BV is linked to increased risk of PTB among pregnant women [5, 6]. Basic evidence of a link between individual and contextual environmental factors and birth outcomes is lacking for pregnant women living in developing nations. A recent case-control study by our group demonstrated that BV and UTI was more common in women using reusable cloth for MHM [3]. The difference was more pronounced in those who changed pads less frequently, and washed and dried them under unhygienic conditions. Use of reusable cloths is more common in socioeconomically-deprived women. Poor MHM likely promotes urogenital disease for a number of various causative organisms, including Trichomnonas vaginalis (TV) and Vulvovaginal candidiasis (VVC). These findings imply that poor hygiene, especially MHM practices promote infection with a broad array of organisms and may contribute to far more urogenital disease burden among women than expected. Results of our longitudinal follow-up study provided the first ever evidence that poor sanitation is associated with higher risk of adverse pregnancy outcomes such as PTB and LBW. Additional studies are required to elucidate the biological basis of this association so that appropriate interventions can be designed for this important and nagging public health problem. The conceptual model of pathways between sanitation access, hygiene practices, and health will evolve as data from our studies and those from others emerge. Life course social stage and geography are critical modifiers of the associations between MHM and reproductive health. Poor MHM impacts on health in women can be acute and lasting in nature, and betemporally elevated during critical life course stages. Menstruation, often, is surrounded by multiple beliefs and social taboos. Women and girls could be the victim of psychosocial stress from unhealthy behavioral practices including not attending religious functions, prohibition of visiting temple and not touching menstruating women, avoiding cooking and eating with others during menstruation, avoiding sex during menstruation, avoid swimming or washing the hair during menstruation, avoid eating certain types of food during menstruation, believing that menstrual blood is impure, taking time off during menstruation, restricting menstruating women to seclusion huts. Numerous studies are trying to prove whether or not these practices are scientific. Experiences from our researches reveled that most women who follow menstrual rituals are not concerned with public health perspectives, rather, it is reverence to an age old belief system that they want to be keepers of. Therefore health education and promotion interventions are warranted. Future research goals should incorporate life-course epidemiology strategies and MHM-associated infection to test whether biological effects of MHM mediate the pathways between poor MHM and reproductive health outcomes, and to assess how effects manifest over the life-course. More

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4.

5.

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Sumpter C and Torondel B (2013). A systematic review of the health and social effects of menstrual hygiene management. PLoS ONE; 8: e62004. Sahoo KC, Hulland KR, Caruso BA, et al (2015). Sanitationrelated psychosocial stress: a grounded theory study of women across the life-course in Odisha, India. Soc Sci Med; 139: 80-9. Das P, Baker KK, Dutta A, et al (2015). Menstrual hygiene practices, WASH access and the risk of urogenital infection in women from Odisha, India. PLoS ONE; 10: e0130777. Padhi BK, Baker KK, Dutta A, et al (2015). Risk of adverse pregnancy outcomes among women practicing poor sanitation in rural India: A Population-Based Prospective Cohort Study. PLoS Med; 12: e1001851. Donders GG, Van Calsteren K, Bellen G, et al (2009). Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG; 116: 1315-24. Abramovici A, Lobashevsky E, Cliver SP, et al (2015). Quantitative polymerase chain reaction to assess response to treatment of bacterial vaginosis and risk of preterm birth. Am J Perinatol; 32: 1119-25.

HEAT STRESS IMPAIRS FOLLICULAR DYNAMICS-STRATEGIES FOR ITS MANAGEMENT Vikash Chandra and G. Taru Sharma* Division of Physiology and Climatology ICAR-IVRI, Izatnagar [email protected]

Climate change and food security are two emerging issues faced by almost every nation. Climate change models predict an increase in the number of extreme weather events, including an increase in the severity and duration of heat waves. Effects of global warming may not be adverse everywhere as areas experiencing severe cold may get beneficial effects in terms of production and reproduction, while a relevant increase of drought is expected across the world affecting forage and crop production, thus adversely affecting production and reproduction. High environment temperatures may compromise reproductive efficiency of farm animals in both sexes and hence negatively affect milk, meat, and egg production and the results of animal selection. High-producing animals are more susceptible to heat stress due to their high metabolic heat production. Heat stress adversely affects ovarian follicle development and 9


[6]. Plasma progesterone secretion is also lowered during heat stress [3]. Low plasma progesterone affects steroidogenesis in the dominant follicle and CL and thereby alters reproductive function in the subsequent estrus cycle. Low progesterone may cause aberrant follicular development which may result in abnormal oocyte maturation in the ovulatory follicles. Delayed effect of heat stress on follicle quality may be overcome by mechanical removal of follicles by OPU from ovaries or by stimulating follicle turnover. FSH treatment increases the number of medium-sized follicles in the follicular waves following heat stress and induced an earlier emergence of high-quality oocytes. Stimulation of gonadal function by GnRH improves follicular function, as frequent follicular waves induced during fall increased follicular estradiol content in preovulatory follicles aspirated from previously heatstressed cows [7]. Synchronization with GnRH and PGF2α also improves fertility [8]. The stage of the estrous cycle at the time of the OPU session influences the recovery rate, oocyte quality, and in vitro embryo production (IVP). Conflicting results have been reported regarding the ideal follicular phase to maximize performance of OPU. Greater recovery rates have been reported when the OPU was performed closer to the follicular wave emergence [9], while greater in vitro competence of oocytes was obtained during the early dominance phase [10]. Increased IVP was achieved when FSH was used in four equal doses twice daily beginning at the time of follicular wave emergence. In this case, OPU was performed 24 h after the last FSH treatment [11]. Although new knowledge about animal responses to the environment continues to be developed, managing livestock to reduce the impact of climate remains a challenge. Among the environmental variables affecting livestock, seems to be one of the more intriguing factors making difficult animal reproduction of many world areas. Heat stress affects animal reproductive health in multiple ways and it is long lasting. Understanding the molecular mechanism of thermal effects on follicle, oocytes and embryos may be helpful in designing new strategies for better reproductive health management in changing climate scenario.

compromises oocyte growth by altering progesterone, the secretion of luteinizing hormone (LH) and folliclestimulating hormone (FSH), and dynamics during the estrus cycle [1]. Heat stress has also been associated with impairment of embryo development and increased embryo mortality. Moreover, heat stress may reduce the fertility of dairy cows by poor expression of estrus due to reduced estradiol secretion from the dominant follicle developed in a low-LH environment. Heat stress can sometimes increase adrenocorticotropin secretion, which itself can block estradiol induced estrus behavior. It is also likely that estrus expression is reduced by the physical lethargy experienced by heat-stressed animals. The preovulatory follicle is a key component of the reproductive systems, and impairment of its function during thermal stress may affect other reproductive events, such as secretion of gonadotropins, progesterone, and estradiol and subsequently the development of the corpus luteum (CL) and embryo. Aberrant follicular development is observed in hot season. Reduction in plasma inhibin concentration was detected in heat-stressed lactating dairy cows [2]. The dominance of the large follicle is suppressed during heat stress, and size of subsequent CL is also compromised [3]. In multiparous animals ovulation rate is also reduced [3]. Reduction in follicular dominance during the period of heat stress is associated with a decrease in inhibin secretion by granulosa cells and subsequent alterations in FSH that leads to an increase in the development of large follicles (e.g., nonovulatory follicles and cysts) in cattle [4]. This may happen due to attenuated follicle dominance, but due to elevated ambient temperature, early embryonic losses occur and pregnancy is not sustained. The pool of small antral follicles gets damaged during summer, and as long as these follicles are sustained in the ovaries, fertility will remain low (after effect of summer). Sensitivity of the early growing follicles to heat stress is a likely explanation for the fact that oocyte quality is only gradually restored in the autumn and that restoration of oocyte competence for cleavage in the autumn can be hastened by treatments that increase follicular turnover [5]. It is speculated that fertility may not be restored until all the damaged follicles destined for ovulation have been removed from the ovary that may be the possible explanation of restoration of fertility in the autumn. Actually the follicle is a multi-compartmental structure in terms of biosynthesis of steroids and intrafollicular communication between the oocyte and follicular tissue. Seasonal variations in follicular steroidogenesis may be because of two reasons: first because of low substrate availability due to lowered feed intake which may be said as “indirect effect” and second by alteration in gonadotropin secretion which in turn may affect follicular function. Heat stress can reduce the magnitude of the preovulatory surge of LH and estradiol-17β. There are also direct effects of elevated temperature on nuclear maturation, spindle formation, cortical granule distribution, free radical formation, mitochondrial function, and apoptosis. Estradiol and androstenedione production by granulosa cells and theca cells is decreased due to heat stress, and the theca cells appeared more susceptible to heat stress. Progesterone plays an important role in follicular turnover 10


positions gradually and so as the climate. It was the adaptability which has greater impact on reproductive health in reference to earth’s land mass shifts [1]. Recent decade has seen increase in reproductive defects among humans, both males and females. At critical point of lifespan of any individual, exposure to the surrounding has very significant effects. Exposure to several factors degrading our environment has been linked to reproductive defects, which may affect us as well as our future generations. Pre-counseling and guidance by health care provider can help us to avoid these defects, specifically by reducing the exposure to reproductive toxicants which are known to cause several irregularities in menstrual cycle, early pregnancy loss, fetel death, premature birth, underweight etc. Water, air, soil, dust, food and consumer products are the major contributor of reproductive toxicants and dominant places of exposure are housing societies, communities, schools, markets and offices. The environmental contaminants interfering to normal reproductive health can be best demonstrated by effect of heavy metals, specifically Lead which can reside in bone for decades. Compounds like pesticides and other similar pollutants also interfere and cause many adverse effects on reproductive outcomes. These compounds have shown negative effects on receptor binding capacity, regulatory process and changes in hormone formation process. Reproductive contaminate exposure depends on threshold level of toxicants, timing of exposure and mechanism of effect of toxicants. Phenytoin (an anti seizure drug) causes birth abnormity by defecting fetal and embryonic development without causing mutations in DNA. Some chemicals are responsible to alter DNA structure by causing genetic mutations. Some chemicals like benzene of industrial origin are also mutagen. Other chemicals, like DES (diethylstilbestrol) causes a delayed epigenetic effect in some reproductive hormones i.e. they change the way of expression of genes related to reproductive outcome. In mid of the century it was believed that DES prevents the miscarriage among pregnant women but later it proved wrong and showed that actually it increases the risk of miscarriage. Some researcher showed experimentally that reproductive abnormalities and reproductive tract carcinoma in offsprings of exposed mother even persist after two generations. PCBs (polychlorinated Biphenyles) are the compounds which were once used in electrical appliances in the form of lubricants and coolants which contaminate air water and soil through use, manufacture, disposal and burning. PCBs can’t be degraded naturally and remain in environment for several years. Its persistence can be compared with DTT because it also accumulates in the fishes and other organisms of that particular food chain. Menstrual disturbances among women, men’s infertility and neonate’s reduced birth weight may be the symptoms of PCBs exposure. Pesticides are other aspects of exposure in individual by contaminated drinking water, food residues, occupational pesticidal exposure and applications. They can also expose from weedicides, insecticides, rodent traps, and

References 1.

Chandra V, Sejian V and Sharma GT (2015). Strategies to improve livestock reproduction under the changing climate scenario. In: Sejian V, et al (Eds.), Climate Change Impact on Livestock: Adaptation and Mitigation. © Springer India; 425-39. DOI 10.1007/978-81-322-2265-1_24. 2. Wolfenson D, Thatcher WW, Badinga L, et al (1995). Effect of heat stress on follicular development during the estrus cycle in lactating dairy cattle. Biol Reprod; 52: 1106-13. 3. Chandra V, Hooda OK, Singh G, et al (2007). Effect of heat stress on follicular development and ovarian steroid hormone in black Bengal goats. Indian J Anim Sci; 77(2):139-43. 4. Wolfenson D, Roth Z and Meidan R (2000). Impaired reproduction in heat stressed cattle: basic and applied aspects. Anim Reprod Sci; 60-61: 535-47. 5. Roth Z, Arav A, Bor A, et al (2002). Effect of treatment with FSH or rbST on the quality of oocytes aspirated in the autumn from previously heat stressed cows. J Dairy Sci; 85: 1398-405. 6. de Castro T, Rubianes E, Menchaca A, et al (1999). Ovarian dynamics, serum estradiol and progesterone concentration during the inter-ovulatory interval in goats. Theriogenology; 52: 399411. 7. Roth Z, Bor A, Braw-Tal R, et al (2004). Carry over effect of summer thermal stress on characteristics of the preovulatory follicle of lactating cows. J Therm Biol; 29: 681-5. 8. Friedman E, Voet H, Reznikov D, et al (2011). Induction of successive follicular waves by gonadotropin-releasing hormone and prostaglandin F2α to improve fertility of high producing cows during the summer and autumn. J Dairy Sci; 94: 2393-404. 9. Machatkova M, Krausova K, Jokesova E, et al (2004). Developmental competence of bovine oocytes: effects of follicle size and the phase of follicular wave on in vitro embryo production. Theriogenology; 61: 329-35. 10. Hendriksen PJM, Steenweg WNM, Harkema JC, et al (2004). Effect of different stages of the follicular wave on in vitro developmental competence of bovine oocytes. Theriogenology; 61: 909-20. 11. Rodriguez P, Tribulo A, Ramos M, et al (2010). Comparison of oocyte recovery rates and morphology obtained by OPU after different hormonal treatments in cattle. In: XXVI World Buiatrics Congress, Santiago, Chile.

ENVIRONMENTAL FACTORS AND REPRODUCTIVE HEALTH Krishna Kant, Anil Kumar Tomar and Savita Yadav* Department of Biophysics All India Institute of Medical Sciences New Delhi [email protected]

The earth’s atmosphere and climate have changed gradually from hot to frigid, wet to dry and vice versa during its 4.5 billion years journey to present condition. During this mammals evolved around 250 millions ago. Some part of Pangaea was in seasonal effect and some are under tropical conditions. So some early mammals adapted to reproduce under specific seasons, whilst some can throughout the year irrespective of climatic conditions. Many species may face extinction if they cannot evolve new seasonal strategies. When Pangaea broke up, the land masses shifted their 11


In summary, to sustain a healthy reproductive life, environment plays a greater role. There are several factors rising due to environmental disturbances which cause infertility resulting in high social pressure and medical burden. Thus, not only for reproductive health but for overall health, it is essential to rebuild and protect our natural surroundings. Figure: Common Environmental Factors Influencing our Reproductive Health.

contaminated dust within and near the home. Atrazine, a chemical which act on photosynthetic process to check weeds is associated with decreased egg production in animals and viability of embryo in birds [2]. Ethylene oxide, a chemical used to kill mould, fungi and bacteria is associated to pregnancy loss. Organophosphates are associated with neurological impairments. Dichloropropane (DBCP) acting for reduced male fertility [3]. Methyl mercury is bioaccumulant in fishes and corresponding food chain. Methyl mercury contamination can be carried out from different sources like seafood; coal- fired power plants etc. Airborne mercury is the primary source of accumulation of mercury in wetlands, lakes and ocean. In aquatic ecosystem several bacteria are responsible for change of inorganic mercury to organic methyl mercury. A north European island ‘Faroe’ is reported to having lower IQ level in children whose mother consuming contaminated sea foods during pregnancy [4]. Benzene, a vapour or liquid is aromatic in structure. It is primarily used in paint remover glues and inks. Presently, benzene is used in dye and plastic industry as a precursor. Benzene exposure has been associated to adverse effects on reproduction [5]. Some socio economic status like poverty, income inequality, poor education discrimination/ marginalization during the life span is also contributing to low reproductive behaviour in human society [6]. Low socio economic status indicated by maternal anthropometry (BMI, gestational weight gain and height) smoking, uses of drugs nutritional level, genital tract infection and inflammation, quality and quantity during gestation period, depression and stress, marital support etc [5-7]. Low socio economic status background women are generally having rich fat/calorie food with very less nutritional value is the cause behind greater rate of some APOs where as adequate food supply by women cause more exposure against oxidative stress, allostatic stress, etc [8-13]. Preeclampsia and gestational diabetes are observed in women exposed to air pollution in recent studies [14-18]. Air pollutants such as carbon mono-oxide (CO), sulfur dioxide (SO2), Nitrogen dioxide (NO2), ozone, polycyclic hydrocarbons, particulate matter have been associated with APOs (adverse pregnancy/ prenatal outcome). Particulate matter (PM) is classified according to particle size in atmosphere like coarse fraction (2.5-10um), respirable fraction (