Reproductive toxicity of combined effects of endocrine disruptors on human reproduction.

Confluence of environmental, genetic, and lifestyle variables is responsible for deterioration of human fecundity. Endocrine disruptors or endocrine disrupting chemicals (EDCs) may be found in a variety of foods, water, air, beverages, and tobacco smoke. It has been demonstrated in experimental investigations that a wide range of endocrine disrupting chemicals have negative effects on human reproductive function. However, evidence on the reproductive consequences of human exposure to endocrine disrupting chemicals is sparse and/or conflicting in the scientific literature. The combined toxicological assessment is a practical method for assessing the hazards of cocktails of chemicals, co-existing in the environment. The current review provides a comprehensive overview of studies emphasizing the combined toxicity of endocrine disrupting chemicals on human reproduction. Endocrine disrupting chemicals interact with each other to disrupt the different endocrine axes, resulting in severe gonadal dysfunctions. Transgenerational epigenetic effects have also been induced in germ cells, mostly through DNA methylation and epimutations. Similarly, after acute or chronic exposure to endocrine disrupting chemicals combinations, increased oxidative stress (OS), elevated antioxidant enzymatic activity, disrupted reproductive cycle, and reduced steroidogenesis are often reported consequences. The article also discusses the concentration addition (CA) and independent action (IA) prediction models, which reveal the importance of various synergistic actions of endocrine disrupting chemicals mixtures. More crucially, this evidence-based study addresses the research limitations and information gaps, as well as particularly presents the future research views on combined endocrine disrupting chemicals toxicity on human reproduction.

Optimization of estrogen dosage for uterine receptivity for implantation in post-coital bilaterally ovariectomized mice.

Estrogens and progesterone, in unison and/or separately, synchronize the distinct events of blastocyst development, uterine priming and receptivity induction for implantation. In contrast to high implantation failure rates, the mechanistic concepts regarding the uterine receptivity for implantation still remain elusive. The present study aims to define the minimum estradiol (E2) dose to induce uterine receptivity for successful implantation in post-coitus bilaterally ovariectomized (BLO) progesterone-primed uterus of mice. Post-coital sperm-positive adult female mice were divided into two groups. In both the groups, delayed implantation was induced by BLO on post-coitus Day 4 (D4). Group 1 received 2 mg of progesterone (P4) from D5 until sacrifice, and E2 injection of 3.0, 10.0, 25.0 and 50.0 ng on D7. On D8, all mice of this group were sacrificed except the mice that received second dose of 25.0 ng of E2 on D8 and were sacrificed on D9. Group 2 followed the same doses, but were given simultaneously on D4, and sacrificed on D5. The mice that received second doses of 25.0 ng E2 were sacrificed on D6. The minimum dose of E2 required to induce uterine receptivity for implantation is a single dose of 50.0 ng E2. The uterus remained refractory following short receptive period at E2 doses lower than 50.0 ng, which is just sufficient to establish desired uterine receptivity. However, repeated administration of sub-threshold doses of 25.0 ng of E2 could also not effectively sustain uterine receptivity towards successful implantation.

Polycystic Ovary Syndrome: An Updated Overview Foregrounding Impacts of Ethnicities and Geographic Variations.

Polycystic ovary syndrome (PCOS) is one of the most common heterogeneous conditions of the endocrine reproductive system in women of childbearing age. Hyperandrogenism and oligomenorrhea are the two core characteristics of PCOS, a complicated and multifaceted illness. The condition is also linked to several major side effects, which include type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. There are few facts and statistics available on PCOS prevalence internationally due to the significant degree of geographic and ethnic variance and inconsistency caused by different diagnosis standards. Limited (n = 179) explorations have been made in the context of the prevalence of this complicated illness so far, and out of these, only 55 studies have discussed its association with race and/or ethnicity. However, those studies remain restricted due to the small sample size, biased selection, and the lack of comparative studies. Variations in PCOS prevalence frequency also arise due to different diagnostic criteria, as well as racial and ethnic differences, associated lifestyle factors, and subsequent illnesses that affect the accuracy of the diagnosis. The main objective behind this systematic review is to provide comprehensive epidemiological data on PCOS that is organized geographically. This evidence-based study also provides an overview of the clinical management of PCOS to instigate further research on this complex endocrinological condition and the subsequent development of preventive treatment strategies.

N-acetyl cysteine as a potential regulator of SARS-CoV-2-induced male reproductive disruptions.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has shown its persistent pandemic strength. This viral infectivity, kinetics, and the mechanisms of its actions in human body are still not completely understood. In addition, the infectivity and COVID-19 severity reportedly differ with patient's gender with men being more susceptible to the disease. Thus, different studies have also suggested the adverse impact of COVID-19 on male reproductive functions, mainly emphasizing on high expressions of angiotensin-converting enzyme 2 (ACE2) in the testes that allows the viral entry into the cells. Main body: The N-acetylcysteine (NAC), a potent therapeutic agent of COVID-19, may be effective in reducing the impairing impacts of this disease on male reproductive functions. NAC acts as mucolytic agent by reducing sulfide bonds in the cross-linked glycoprotein matrix in mucus owing to its free sulfhydryl group. Since NAC also breaks the viral disulfide bonds required for the host cell invasion, it may help to prevent direct SARS-CoV-2 invasion into the testicular cells as well. NAC also acts as a potent anti-inflammatory and antioxidant, directly scavenging reactive oxygen species (ROS) and regulating the redox state by maintaining the thiol pool being a precursor of cysteine (an essential substrate for glutathione synthesis). Since it is suggested that male reproductive impairment in COVID-19 patient may be caused by secondary immune responses owing to systemic inflammation and OS, the anti-inflammatory and antioxidant properties of NAC explained above may attribute in protecting the male reproduction functions from these COVID-19-mediated damages. Conclusion: This article explains the mechanisms how NAC treatment for COVID-19 may prevent the infection-mediated disruptions in male reproduction.

Environmental and occupational exposure of metals and female reproductive health.

Untainted environment promotes health, but the last few decades experienced steep upsurge in environmental contaminants posing detrimental physiological impact. The responsible factors mainly include the exponential growth of human population, havoc rise in industrialization, poorly planned urbanization, and slapdash environment management. Environmental degradation can increase the likelihood of human exposure to heavy metals, resulting in health consequences such as reproductive problems. As a result, research into metal-induced causes of reproductive impairment at the genetic, epigenetic, and biochemical levels must be strengthened further. These metals impact upon the female reproduction at all strata of its regulation and functions, be it development, maturation, or endocrine functions, and are linked to an increase in the causes of infertility in women. Chronic exposures to the heavy metals may lead to breast cancer, endometriosis, endometrial cancer, menstrual disorders, and spontaneous abortions, as well as pre-term deliveries, stillbirths. For example, endometriosis, endometrial cancer, and spontaneous abortions are all caused by the metalloestrogen cadmium (Cd); lead (Pb) levels over a certain threshold can cause spontaneous abortion and have a teratogenic impact; toxic amounts of mercury (Hg) have an influence on the menstrual cycle, which can lead to infertility. Impact of environmental exposure to heavy metals on female fertility is therefore a well-known fact. Thus, the underlying mechanisms must be explained and periodically updated, given the growing evidence on the influence of increasing environmental heavy metal load on female fertility. The purpose of this review is to give a concise overview of how heavy metal affects female reproductive health.

Waist-to-height ratio and BMI as predictive markers for insulin resistance in women with PCOS in Kolkata, India.

PURPOSE: Polycystic ovarian syndrome (PCOS) is most commonly presented with insulin resistance (IR). Simple anthropometric indices may serve as surrogate markers of these conditions with population-based cut-off values. The present study suggests the cut-off values of waist-to-height ratio (WHtR) and body mass index (BMI) in early prediction of PCOS and IR in PCOS women based in Kolkata, a major metropolitan city in India. METHODS: This cross-sectional study included 66 women (aged 16-30 years) from Kolkata, India, with confirmed PCOS, using Rotterdam criteria. IR was defined following the homeostasis model assessment (HOMA). Anthropometric and biochemical data were obtained using standard protocol and compared among the PCOS subjects grouped as per IR prevalence, BMI, and WHtR values. The receiver operating characteristics (ROC) curve was applied to evaluate and compare the cut-off values of WHtR and BMI in the prediction of PCOS and IR in women with PCOS. RESULTS: As per ROC analysis, WHtR showed significantly higher AUC in the detection of PCOS and IR in PCOS subjects respectively, than that of BMI. The cut-off values of WHtR and BMI for PCOS were 0.560 and 28.47 respectively, and for IR in PCOS patients, were 0.620 and 29.14 respectively. CONCLUSIONS: The present study suggests a cut-off value of WHtR to be used as an inexpensive and noninvasive screening tool for early prediction of PCOS and IR among PCOS afflicted women based in Kolkata, India and for this prediction, the study also claims WHtR as a better index than BMI.

Do lifestyle practices impede male fertility?

Alongside an increasing prevalence of couple and male infertility, evidence suggests there is a global declining trend in male fertility parameters over the past few decades. This may, at least in part, be explained through detrimental lifestyle practices and exposures. These include alcohol and tobacco consumption, use of recreational drugs (e.g., cannabis, opioids and anabolic steroids), poor nutritional habits, obesity and metabolic syndrome, genital heat stress (e.g., radiation exposure through cell phones and laptops, prolonged periods of sitting, tight-fitting underwear and recurrent hot baths or saunas), exposure to endocrine-disrupting chemicals (e.g., pesticide residue, bisphenol A, phthalates and dioxins) and psychological stress. This review discusses these lifestyle practices and the current evidence associated with male infertility. Furthermore, known mechanisms of action are also discussed for each of these. Common mechanisms associated with a reduction in spermatogenesis and/or steroidogenesis due to unfavourable lifestyle practices include inflammation and oxidative stress locally or systemically. It is recommended that relevant lifestyle practices are investigated in clinical history of male infertility cases, particularly in unexplained or idiopathic male infertility. Appropriate modification of detrimental lifestyle practices is further suggested and recommended in the management of male infertility.

Viral Pandemics of the Last Four Decades: Pathophysiology, Health Impacts and Perspectives.

The twenty-first century has witnessed some of the deadliest viral pandemics with far-reaching consequences. These include the Human Immunodeficiency Virus (HIV) (1981), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002), Influenza A virus subtype H1N1 (A/H1N1) (2009), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012) and Ebola virus (2013) and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2019-present). Age- and gender-based characterizations suggest that SARS-CoV-2 resembles SARS-CoV and MERS-CoV with regard tohigher fatality rates in males, and in the older population with comorbidities. The invasion-mechanism of SARS-CoV-2 and SARS-CoV, involves binding of its spike protein with angiotensin-converting enzyme 2 (ACE2) receptors; MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), whereas H1N1 influenza is equipped with hemagglutinin protein. The viral infections-mediated immunomodulation, and progressive inflammatory state may affect the functions of several other organs. Although no effective commercial vaccine is available for any of the viruses, those against SARS-CoV-2 are being developed at an unprecedented speed. Until now, only Pfizer/BioNTech's vaccine has received temporary authorization from the UK Medicines and Healthcare products Regulatory Agency. Given the frequent emergence of viral pandemics in the 21st century, proper understanding of their characteristics and modes of action are essential to address the immediate and long-term health consequences.

Evidence for decreasing sperm count in African population from 1965 to 2015.

PURPOSE: This meta-analysis, following our previous reports those documented an overall 57% diminution in mean sperm concentration around the globe over past 35 years and 32.5% decline in past 50 years in European population, attempts to report the declining trend of sperm concentrations in African population between 1965 and 2015. METHODS: In the course of retrieval of data following MOOSE guidelines and PRISMA checklist, we found a total of fourteen studies that have been conducted during that period on altering sperm concentration in the African male. RESULTS: Following analysis of the data, a time-dependent decline of sperm concentration (r = -0.597, p = 0.02) and an overall 72.6% decrease in mean sperm concentration was noted in the past 50 years. The major matter of concern is the present mean concentration (20.38×106/ml) is very near to WHO cut-off value of 2010 of 15×106/ml. Several epidemic diseases, genital tract infection, pesticides and heavy metal toxicity, regular consumption of tobacco and alcohol are reported as predominant causative factors. CONCLUSION: This comprehensive, evidence-based meta-analysis and systematic review concisely presents the evidence of decreased sperm concentration in the African male over past 50 years with possible causative factors to serve the scientific research zone related to male reproductive health.