Sunil Kumar

Bio: Sunil Kumar is an academic researcher from National Institute of Occupational Health. The author has contributed to research in topics: Semen quality & Areca. The author has an hindex of 17, co-authored 54 publications receiving 1221 citations.

Occupational exposure associated with reproductive dysfunction.

Abstract: Evidence suggestive of harmful effects of occupational exposure on the reproductive system and related outcomes has gradually accumulated in recent decades, and is further compounded by persistent environmental endocrine disruptive chemicals. These chemicals have been found to interfere with the function of the endocrine system, which is responsible for growth, sexual development and many other essential physiological functions. A number of occupations are being reported to be associated with reproductive dysfunction in males as well as in females. Generally, occupations involving the manufacture/or application of some of the persistent chemicals that are not easily degradable as well as bio-accumulative chemicals, occupations involving intensive exposure to heat and radiation, occupations involving the use of toxic solvents as well as toxic fumes are reported to be associated with reproductive dysfunction. Occupational exposure of males to various persistent chemicals have been reported to have male mediated adverse reproductive outcomes in the form of abortion, reduction in fertility etc. with inconclusive or limited evidence. Nevertheless, there is a need for more well designed studies in order to implicate any individual chemical having such effects as in most occupations workers are exposed to raw, intermediate and finished products and there are also several confounding factors associated with lifestyles responsible for reproductive dysfunction. There is an urgent need to look at indiscriminate use of persistent chemicals especially pesticides and persistent organic pollutants (POP's) as these chemicals enter the food chain also and could be potential for exposure during the critical period of development. It is also necessary to impart information, and to educate about the safe use of these chemicals, as a very sensitive reproduction issue is involved with exposure to these chemicals. Occupational exposures often are higher than environmental exposures, so that epidemiological studies should be conducted on these chemicals, on a priority basis, which are reported to have adverse effects on reproduction in the experimental system.

Cadmium toxicity: effects on human reproduction and fertility.

Abstract: Background Cadmium (Cd) is a non-essential toxic heavy metal, an environmental toxicant, and toxic at a low concentration, and it has no known beneficial role in the human body. Its exposure induces various health impairments including hostile reproductive health. Objective The present review discusses the information on exposure to Cd and human reproductive health impairments including pregnancy or its outcome with respect to environmental and occupational exposure. Methods The present review provides current information on the reproductive toxic potential of Cd in humans. The data were collected using various websites and consulting books, reports, etc. We have included recent data which were published from 2000 onward in this review. Results Cd exposure affects human male reproductive organs/system and deteriorates spermatogenesis, semen quality especially sperm motility and hormonal synthesis/release. Based on experimental and human studies, it also impairs female reproduction and reproductive hormonal balance and affects menstrual cycles. Based on the literature, it might be concluded that exposure to Cd at low doses has adverse effects on both human male and female reproduction and affects pregnancy or its outcome. Further, maternal prenatal Cd exposure might have a differential effect on male and female offspring especially affecting more female offspring. Hence, efforts must be made to prevent exposure to Cd. Conclusion Cd affects both male and female reproduction, impairs hormone synthesis/regulation and deteriorates pregnancy rate or its outcome even at lower doses.

Occupational, environmental and lifestyle factors associated with spontaneous abortion

Abstract: Scientific evidence indicates extreme exposure sensitivity of embryos, fetuses, and infants to the persistent environmental/occupational chemicals directly and or indirectly as compared to the same magnitude of exposure in adults. Paternal/maternal exposure to some of these chemicals might have a effect on the gamete structure and function, which might have significant implication for the adverse effect on pregnancy and their outcome. The available data point that some of the organochlorine chemicals such as dichlorodiphenyl trichloroethane (DDT); metals such as lead, mercury; industrial pollutants such as dioxin, organic solvents, radiations; and some of the lifestyle-associated factors such as tobacco smoking (active and passive) and excessive maternal intake of alcohol had adverse effect on pregnancy outcome. The existing data support the hypothesis that, in general, working women have a higher risk of undesirable reproductive outcomes, even though the data are scanty. Studies are needed to find out the effects of those reproductive toxicants on priority basis which have been proved to be toxic in animal studies as well as data on human related to these chemicals are scanty. There is a need to educate the childbearing women to avoid exposure to the known or suspected risk factors and their employers to take measures to reduce the toxicant levels in workplace.

Effect of chewing a mixture of areca nut and tobacco on periodontal tissues and oral hygiene status.

Abstract: The present study was conducted to clarify the effects of chewing a quid containing areca nut and tobacco on periodontal tissue and oral hygiene status. A total of 365 subjects (168 chewers and 197 non-chewers with a mean age of 32.5 +/- 0.7 and 30.4 +/- 0.8 years, respectively) were enrolled. Clinical data on periodontal tissues, oral hygiene status, as well as information on bleeding from gums, ulcers in the oral cavity, or a burning sensation in the soft tissues, were collected as indicators of the possible presence and extent of periodontal lesions. The results indicated that a significantly higher number of quid-chewers suffered bleeding from the gums, halitosis, difficulty in opening the mouth and swallowing solid food, a burning sensation in the soft tissues, and ulcers in the oral cavity than non-chewers. There was no significant difference between quid-chewers and non-chewers with respect to oral hygiene measures adopted. However, clinical examination using the oral hygiene index score indicated that the oral hygiene status of quid-chewers was significantly deteriorated. The effect of quid-chewing on the periodontium, i.e. the occurrence of periodontal pockets, gingival lesions and gum recession, were significantly higher in quid-chewers than in non-chewers. Age, sex and smoking adjusted odds ratios for quid-chewers against non-chewers using logistic regression analysis indicated that, in general, chewers were at significantly higher risk for various oral complaints and periodontium status. The present data indicate that chewing quid comprising areca nut and tobacco has adverse effects on periodontal tissues, oral hygiene and incidence of oral lesions.

EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

Abstract: The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

The effects of oxidative stress on female reproduction: a review

Abstract: Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.

The Effects of Cadmium Toxicity

Abstract: Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower (Helianthus annuus L.), Indian mustard (Brassica juncea), and river red gum (Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO2 and Al2O3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.

Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

Abstract: Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.