Sulagna Dutta

Men and mice: Relating their ages

Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail.

Gentamicin in Combination with Ascorbic Acid Regulates the severity of Staphylococcus aureus Infection–Induced Septic Arthritis in Mice

To study the effects of gentamicin in combination with ascorbic acid on septic arthritis, mice were infected with Staphylococcus aureus (S. aureus) and treated with gentamicin, which was given at 5 mg/kg after 24 h of infection, followed by ascorbic acid, given at 20 mg/kg body weight after 2 h of gentamicin treatment. Mice were sacrificed at 3, 9, 15 days post‐infection (dpi). Combined treatment of infected mice with gentamicin and ascorbic acid eradicated the bacteria from the blood, spleen and synovial tissue and showed a significant gross reduction in arthritis, reduced serum levels of tumour necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ). S. aureus‐infected mice have demonstrated the disturbed antioxidant status measured in terms of cellular antioxidants like reduced glutathione and antioxidant enzymes such as superoxide dismutase (SOD) and catalase. The same were ameliorated when the animals were co‐treated with gentamicin along with ascorbic acid.

The Disappearing Sperms: Analysis of Reports Published Between 1980 and 2015

Reports regarding the changes in sperm concentration in different counties of the world are inconsistent. Furthermore, the reports that sprung up from specific epidemiological and experimental examinations did not include data of prior studies or geographical variations. The current study, following a previous report of massive fall in semen volume over the past 33 years, attempts to delineate the trend of altering sperm concentrations and factors responsible for this by reviewing article published from 1980 to July 2015 with geographic differences. The current study identified an overall 57% diminution in mean sperm concentration over the past 35 years (r = −.313, p = .0002), which, when analyzed for each geographical region, identified a significant decline in North America, Europe, Asia, and Africa. An increasing trend of sperm concentration was identified only in Australia. The association of male age with such a trend (R2 = .979) is reported. The authors also correlated male fertility with sperm concentration. Thus, this comprehensive, evidence-based literature review aims to concisely and systematically present the available data on sperm concentration from 1980 to 2015, as well as to statistically analyze the same and correlate male health with the declining pattern of sperm count in a single scientific review to serve the scientific research zone related to reproductive health. It points to the threat of male infertility in times ahead.

Decline in sperm count in European men during the past 50 years

Purpose: To investigate whether the sperm concentration of European men is deteriorating over the past 50 years of time. Materials and Methods: We analysed the data published in English language articles in the past 50 years in altering sperm concentration in European men. Results: A time-dependent decline of sperm concentration (r = −0.307, p = 0.02) in the last 50 years and an overall 32.5% decrease in mean sperm concentration was noted. Conclusion: This comprehensive, evidence-based meta-analysis concisely presents the evidence of decreased sperm concentration in European male over the past 50 years to serve the scientific research zone related to male reproductive health.

Rabbits and men: relating their ages

Abstract Rabbit, a member of the Lagomorpha order, is the closest phylogenetic relative to humans, next to primates. It possesses greater acceptability as a laboratory mammal than primates in terms of husbandry, breeding ease, cost effectiveness, and legal ethical conveniences. Moreover, as a laboratory animal, the rabbit also owns its advantages over mice or rats, in terms of phylogenetic resemblance to human, size, blood volume, responsiveness, and other congruences enabling them to better imitate human physiological characteristics in biomedical research. A specific research aspires to effectuate its outcome on a particular human age group, for which it is pivotal to select a laboratory rabbit of exact age, which will correlate with that specific age of a human, which is currently based on mere approximation. This article is the first ever scientific venture, focused to swap this approximation of laboratory rabbit age with accuracy by relating it with that of humans analyzing different phases of life individually. Considering the diminutive lifespan of rabbits compared to humans, the correlation of their age with respect to the entire lifespan, which we found out to be 45.625 days compared to one human year, is not enough. Thereby, like our previous articles that formulated concise relation of age of laboratory rats and mice with human age, in this article also, we aim to aid biomedical research specificity in the selection of laboratory model age, separately correlating different life phases of humans with that of rabbits, the second mostly used mammal in 2016 in the United States.

Thyroid Disorders and Semen Quality

Thyroid hormones and their impacts on male reproduction have been reported in numerous studies in past few decades. They are the crucial players in the regulation of male gonadal developments and reproductive functions. An excess or deficit of thyroid hormones not only alter the testicular functions but also interrupts neuroendocrine axis through the crosstalk between hypothalamic-pituitary-thyroid (HPT) axis and hypothalamic-pituitary-gonadal (HPG) axis. These changes result in decreased testosterone level and altered seminal plasma components which affect semen quality. The reports on the direct effects of thyroid disorders on semen quality are scanty. Thus, this review scrutinizes the available literature and aims to elucidate (a) the normal thyroidal regulations of semen parameters, (b) effects of hypothyroidism on semen quality (c) effects of hyperthyroidism on semen quality, and (d) the possible mechanism of action of thyroid dysfunctions on the alterations of semen quality. This review also highlights the limitations of the studies carried out so far and accentuates the necessity of large-scale human studies and animal studies specifically focusing on the molecular events of thyroid disorder-induced alterations in semen quality.

Functions of follicular and marginal zone B cells in pregnancy

Pregnancy is a physiological condition when immune cells face a dual crisis, as on one hand, the body needs to essentially tolerate semi-allogenic fetus possessing antigens from maternal and paternal sides, while on the other hand the maternal as well as the fetal body must not be adversely affected by infections. This delicate balance between immune tolerance and responses is regulated by an orchestra of immune cells. Various immune regulations by B cells are lately being explored. These include the production of asymmetric antibodies, induced by pregnancy factors, providing protection against maternally derived antipaternal symmetric antibodies at the feto-maternal interface[1] to protect the fetus from immune attack by destructive maternal natural killer cells as well as cytotoxic lymphocytes[2]. Moreover, the regulatory B cells can inhibit pro-inflammatory responses triggered by T cells and pro inflammatory mediators during pregnancy, by secreting interleukin10, a potent anti-inflammatory cytokine[3]. Interleukin-10, secreted by B cells, also suppresses activities of the dendritic cells and keeps them in an immature state as mature dendritic cells would induce T cells which are detrimental to pregnancy sustenance[4]. B cells are the pioneer cells in humoral immunity, being released from the bone marrow and attaining ultimate maturation while they encounter antigen in the secondary lymphoid organs, producing plasma cells and memory cells. In spleen and lymph nodes, the pro B cells develop either into follicular (FO) B cells or marginal zone (MZ) B cells[5]. Once encountering an antigen, FO B cells get activated by T cells and differentiate into high-affinity immunoglobulin G (IgG)-producing plasma cells as well as memory B cells[6,7], providing specific immune defence lasting for about 5 days. On the contrary, the MZ B cells can be more quickly activated without any requirement of T cell signals owing to their preactivated phenotype and strategic localization in the marginal sinus area of lymph node and spleen. The MZ B cells differentiate into short-life plasma cells generating low-affinity antibodies[8], mainly IgM and IgA natural antibodies, which regulate the first wave of an infection. Pregnancy may be maintained by the inhibition of the highly specific FO B cells to restrict rejection of the semi-allogenic fetus by maternal immune responses, and expansion of MZ cells in normal pregnancy to compensate the reduced number of FO B cells in combating infections. In a recent study, female CBAJ mice which were crossed either with DBA/2J male mice had immune-mediated pregnancy disturbances[9], while the CBAJ mice mated with BALB/c male mice showed normal pregnancy outcome. It supported the notion of overall reduced B cell lymphopoiesis in pregnancy irrespective of the pregnancy outcome as all the pregnant mice whether with normal pregnancy or with pregnancy disturbances showed significant reduction in total number of pro and pre B cells, as compared to nonpregnant control mice. But in spite of significant diminution of FO B cells in normal and disturbed pregnancy compared to nonpregnant ones, an expansion of MZ B cells was pronounced only in the pregnant mice with normal pregnancy outcome. In addition, higher IgM in the serum of normal pregnant mice compared to disturbed pregnant group as well as nonpregnant mice, confirm that in normal pregnancy, the immune suppression Asian Pacific Journal of Reproduction 2018; 7(4): 191-192

Sperm counts in Asian men: Reviewing the trend of past 50 years

Objective: To reveal the trend in alterations of sperm counts in Asian men over the past 50 years. Methods: This study reviewed all the published reports to unveil the specific pattern of alterations of sperm concentrations in Asian men from 1965 till 2015. The time-related changes in sperm concentration were studied using linear regression analyses. Results: The present study elucidated the trend using the reports from Carlsen et al (1965-1990) and non-Carlsen studies published until 2015, on fertile Asian men. In the reports of Carlsen et al, no overall declining trend in Asian men (r = 0.509, P = 0.760) was observed during this tenure, but non- Carsen reports showed a significant time-dependent decline of sperm concentration (r = -0.754, P = 0.005) in Asian men. This present review also showed a mild time-dependant decline in sperm concentration (-0.44×106/mL/year, 95% CI: -0.65 to -0.23; r = -0.473, P = 0.040) which accounted for an overall 22.17% decrease in past 50 years. Conclusions: This study brings to the forefront that sperm concentration among Asian men follows a mild declining trend over the period of 50 years, and further studies addressing the causes of this decline are required.

Oxidative stress-induced alterations in seminal plasma antioxidants: Is there any association with keap1 gene methylation in human spermatozoa?

Kelch‐like ECH‐associated protein 1 (keap1)‐nuclear factor‐erythroid 2‐related factor 2 (Nrf2) pathway is one of the master regulators of cellular defence against oxidative stress. Epigenetic alterations like hypermethylation of keap1 gene impair keap1‐Nrf2 system in several oxidative stress–associated diseases. The objective of this study was to evaluate the epigenetic status of keap1 in sperm DNA of normozoospermic subjects, having different levels of reactive oxygen species (ROS) in seminal plasma. Semen samples were obtained from 151 apparently healthy male partners of couples who attended the Avicenna infertility clinic. Samples were categorised into four groups according to their ROS levels: group A (n = 39, ROS < 20 RLU/s per 106 spermatozoa), group B (n = 38, 20 ≤ ROS < 40 RLU/s per 106 spermatozoa), group C (n = 31, 40 ≤ ROS < 60 RLU/s per 106 spermatozoa) and group D; (n = 43, ROS ≥ 60 RLU/s per 106 spermatozoa). Keap1 methylation status was assessed using methylation‐specific PCR along with seminal total antioxidant capacity. The results showed no significant alterations in keap1 methylation in any groups, whereas the total antioxidant capacity enhanced with increasing levels of ROS exposure. These results indicate that keap1 was not methylated during ROS elevation and oxidative stress, suggesting that the cells have adopted other mechanisms to elevate antioxidant level.

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.