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 Carlsenet al(1965-1990) and non-Carlsen studies published until 2015, on fertile Asian men. In the reports of Carlsenet 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.

Obesity, endocrine disruption and male infertility

Obesity has become a global pandemic since the last few decades with prevalence in more than one-third of the population in the United States. Another concurrent global health concern is the declining trend in male fecundity in terms of semen quality. Male infertility etiology is multifactorial with obesity serving as one of the major causatives. An array of research is directed in unveiling the potential mechanism underlying the obesity-induced male subfertility or infertility. Obesity may alter the hormonal milieu of the hypothalamic-pituitary-gonadal axis, its crosstalks with other metabolic hormones, upregulates secretion of adipose tissue-derived hormones and other factors, thus influencing the endocrine regulation of male reproduction. Obesity may also directly impair testicular functions by inducing genetic and epigenetic alterations in spermatozoa, disrupting sperm morphology and functions. Given the complexity of the condition of obesity and the multivariate etiopathology of male subfertility/ infertility, this review is aimed to provide an updated concept on how obesity mediated hormonal modulation may affect male fertility parameters.

Male reproductive hormones and semen quality

Male reproductive functions are mediated by different hormones whose orchestrations remain a major research interest. The 'master' regulator hormonal axis is the hypothalamo-pituitary-gonadal/testicular axis which is led by the pulsatile release of hypothalamic gonadotropin-releasing hormone. This, in turn, stimulates the anterior pituitary trophic hormones, the luteinizing hormone and follicle-stimulating hormone. Luteinizing hormone and follicle-stimulating hormone act upon the testicular cells, the Leydig cells for steroidogenesis and Sertoli cells to aid spermatogenesis, respectively. This primary axis is influenced by an array of other testicular hormones, metabolic hormones, and different regulatory factors. These hormonal crosstalks influence the intricate testicular functions, sexual behavior and semen quality in men. Given the growing concern in the last few decades over the increasing prevalence of male subfertility and/or infertility mostly in terms of deteriorating semen quality, it is required to find its underlying mechanisms. In this regard, the endocrine regulation of testicular functions is of prime importance in the determination of semen quality and sperm functions. This review article aims to present a concise updated overview on the mechanism by which the key hormones integrate the male reproductive functions and maintain the semen quality.

Obestatin in male reproduction and infertility

Obestatin is a 23-amino acid peptide hormone secreted by the stomach and is found in several tissues all over the body, such as the gastric mucosa, spleen, mammary gland, plasma as well as in the testicular Leydig cells. Obestatin seems to operate as part of the integrated gut-brain network acting as an anorectic hormone, reducing food intake and reversing body weight gain. Besides the expressions of obestatin in male reproductive tissues, it is also shown to increase testosterone secretions, thus ameliorating testicular functions. In the present scenario where the increasing prevalence in obesity is considered as one of the major causatives of worldwide declining trend of semen quality, molecules like obestatin playing roles in both metabolic and reproductive functions find importance in management of obesity-induced male infertility or subfertility. The present review article aims to provide updated concepts on obestatin and its mode of actions, and its role in modulation of male reproductive functions.

Thyroid hormones in male reproduction and infertility

Thyroid hormones have been well studied for its relevance to male reproduction in the last few decades. They are considered as essential regulators of male reproductive functions and play vital roles in male gonadal developments. Hyperthyroidism and hypothyroidism both affect testicular functions and influence neuroendocrine regulations over reproductive functionsvia the crosstalk between the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. The alterations in the male reproductive hormonal milieu by thyroid hormones may lead to reduced testosterone levels and deterioration of semen quality. However, there are very few reports on the direct effects of thyroid disorders upon testicular functions and semen quality. This article aims to review the available literature to present a concise updated concept on the regulation of male reproductive functions by the thyroid hormones, and the possible mechanism by which thyroid dysfunctions affects testicular functions.

Leptin and male reproduction

The global scenario reveals that the recent trend of deterioration of male fertility parameters parallels the growing prevalence of obesity. Over the last few decades, substantial research evidence has surfaced that aid understanding of the mechanisms by which body energy homeostasis is associated with reproductive functions. In this regard, leptin, an adipocyte-derived hormone, finds utmost relevance for its versatile physiological functions especially in metabolism as well as in the regulation of reproductive functions. Since leptin receptors are found to be highly expressed in several structures, both centrally and peripherally, it has been hypothesized that leptin may affect reproductive functions either via the hypothalamic-pituitary-gonadal axis or may also directly act upon gonadal tissues. Its roles, particularly during puberty and reproduction, are well documented. However, the exact mechanisms of leptin actions upon the gonadotropin-releasing hormone neurons to induce physiological changes of puberty and reproduction need further research. Leptin is proven as an essential hormone required for normal reproductive functions, but when leptin levels exceed the physiological limit, it may adversely affect the testicular processes. Leptin can serve as a potential link between obesity and male infertility, as it has been shown that poor male reproductive parameters such as low sperm count, testicular oxidative stress, high rate of morphological abnormalities in sperm, positively correlate with increased levels of leptin in obese men. Therefore, the present review article aims to provide a better understanding of the updated views on the functions of leptin and mechanisms of leptin actions on male reproduction.

Ghrelin and male reproduction

Ghrelin is a multifunctional peptide hormone, conventionally known to be secreted by the stomach. The synthesis of ghrelin by the reproductive organs signifies its autocrine and/or paracrine actions upon the gonads. Expression of the functional ghrelin receptor is observed in different levels of the hypothalamic-pituitary-gonadal axis, suggesting its action on hypothalamic secretion of gonadotropin-releasing hormone and the pulsatile secretion of pituitary gonadotropins. It mainly acts to inhibit the secretion of the luteinizing hormone and thereby may also hinder proper testicular functions. This review article aims to provide a concise concept on (a) the characteristics, secretion and mode of actions of ghrelin, and (b) the role of ghrelin as a potential regulator of male reproductive functions. It may act upon the hypothalamic-pituitary-gonadal axis as well as directly regulate key testicular functions such as testosterone secretion, Leydig cell proliferation and expressions of prime functional proteins in the seminiferous tubule. These actions of ghrelin on testicular functions appear to be species-specific. Ghrelin and its versatile biological functions bring to a consensus that further research on ghrelin may establish one of the associations between body energy status with alterations in male reproductive functions.

Orexins and male reproduction

Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.

Adiponectin in male reproduction and infertility

Adiponectin is an adipokine that has the highest plasma concentration among all other adipokines. It is a white adipose tissue secretion essential for the regulation of energy metabolism owing to its antiatherogenic insulin-resistance, and anti-inflammatory properties. Studies have put forth that adiponectin is a potent endocrine regulator with mechanisms relating energy balance with reproductive function in different species, including humans. The two adiponectin receptors, AdipoR1 and AdipoR2 have been found to be expressed in the prime regulatory axis of reproduction, the hypothalamic-pituitary-gonadal axis. The activation of adiponectin receptors has been shown to regulate the secretion and gene expressions of kisspeptin, gonadotropin-releasing hormone and gonadotropins. Adiponectin finds relevance in the regulations of most of the vital testicular functions, such as steroidogenesis, germ cell proliferation and their coordinated apoptosis, as well as in modulation of testicular redox status and oxidative stress. Since metabolic syndrome and their associations with male infertility have been gaining immense research interest, adiponectin seems to be one of the important mediators of metabolic syndrome-induced male reproductive dysfunctions. This article aims to review the patterns of adiponectin expression in the male reproductive tissues and the mechanism by which adiponectin modulates male reproductive functions.

Role of melatonin in male reproduction

Melatonin, conventionally accepted as a pineal gland secretion, is a neuromodulator whose physiological concentrations are regulated by circadian rhythms. Alteration in melatonin levels owing to circadian influences is a major regulator of reproductive functions in animal species that are seasonal breeders. Attributing to its antioxidant properties and capability to cross physiological barriers, such as the blood-brain barrier, the blood-testis barrier as well as having almost no toxicity, melatonin finds high relevance in amelioration of male fertility parameters. Melatonin may affect male reproductive functions by influencing the release of hypothalamic gonadotropin-releasing hormone and pituitary luteinizing hormone, which are among the key hormones in regulation of male reproduction. It may directly act on testicular cells to influence testicular functions. The property of melatonin most essential for testicular functions is its ability to scavenge free radicals, thereby preventing testicular oxidative damage. This article summarizes the updated data on the versatility of melatonin as an endogenous rhythm setter, as an antioxidant molecule and its possible physiological impacts in male reproductive functions.

Functions of follicular and marginal zone B cells in pregnancy

Dear Editor, 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 interleukin-10, 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].

Hormones in male reproduction and fertility

Male factor infertility accounts for about half of overall global infertility cases(1)It involves complex pathophysiological mechanisms(2)Since male reproductive functions are fine-tuned by orchestrated regulation of reproductive hormones, better understanding of male hormonal imbalance and the influence of their crosstalk with metabolic hormones, neuropeptides, and stress markers,etc. will potentiate further research in this direction.

Cytokine landscapes of pregnancy:mapping gestational immune phases

Background Synchronised physiological adaptations occur during pregnancy to achieve systemic,immune and neuroendocrine equilibrium in the mother's body,allowing semiallogenic fetal growth.Main text Depending on the cytokine profile alterations occurring through pregnancy,the latter can be divided into three distinct phases.In the first immunological phase of pregnancy,proinflammatory cytokines promote inflammatory reactions needed for implantation.In the second phase,a possible change from proinflammatory to anti-inflammatory cytokines creates a symbiosis between maternal and fetal components,ensuring fetal development.In the third phase,inflammatory and cytolytic cytokines operate again to reinforce an inflammatory environment for parturition.The article offers a detailed account of immune adaptations during pregnancy and highlights the distinctive cytokine profiles that mark each phase.Conclusion By providing a simplified depiction of pregnancy phases based on cytokine profiles,the article aims to inspire more research in reproductive immunology and improve the management of pregnancy-related inflammation and infection.

Comparative efficacy of ChatGPT 3.5,ChatGPT 4,and other large language models in gynecology and infertility research

Dear Editor,As experts in gynecology and infertility research,we have witnessed the rapid advancement of artificial intelligence(Al)technologies,particularly language models,which have greatly improved their capabilities.In this communication,we aim to compare the proficiency of advanced language models,such as Chat Generative Pre-Trained Transformer(ChatGPT)3.5,ChatGPT 4,and others,in relation to our field.

Impact of industrial revolution 4.0 on reproductive health and infertility management

Fourth Industrial Revolution also known as the Industrial Revolution 4.0(IR 4.0),has brought significant changes and advancements in various industries,including healthcare.1 The integration of advanced technologies such as artificial intelligence(AI),the Internet of Things(IoT),and big data analytics has transformed the way healthcare is delivered and has led to significant benefits for human health.