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Infertility is a common issue. In India, it has doubled in prevalence, raising health issues in both individuals and communities. Couples who are infertile suffer emotionally, socially, and financially. The Indian Society of Assisted Reproduction estimates that there are up to 27.5 million infertile persons living in India, both men and women. Endocrine disruptors, environmental stress, and abnormalities/imbalances in the body’s natural antioxidant defence mechanism all put male fertility at greater risk. Studies on how high altitude affects male fertility are very few. Recent research has shown that oxidative stress from different sources impairs spermatogenesis and causes an imbalance in the level of male hormones. There are two primary causes of oxidative stress: extrinsic and intrinsic, responsible for free-radical generation. There is an internal antioxidant defence mechanism that scavenges the reactive oxygen species, i.e., free radical generation which neutralizes oxidative stress. These antioxidants are important for the protection of cellular integrity. Apart from the antioxidants, various food supplements like melatonin, vitamin C, vitamin E, carotenoids, cysteines, etc., are suitable antioxidants for improving male fertility. Therefore, there is a great need for information on some clinically examined edible phytooxidants, including melatonin, for amelioration of oxidative stress-induced male infertility. This review focuses on the information available as of now about free radical (ROS)-induced reproductive damages in the plains and the high-altitude regions and the role of various antioxidants, including melatonin, in male infertility.

As a transducer of the environmental factors the pineal gland, together with the metabolically active thyroid gland, plays a major role in control of reproduction during different times of the year, in response to the changing environmental conditions of the tropical zone unlike in the temperate zone. Our avian model P. asiatica is a long day breeder. It is reproductively active during summer and quiescent during winter months. In this study we investigated the role of thyroid gland super-imposed by melatonin in the regulation of the annual male reproduction in this bird. The metabolically active thyroid gland presented a functional parallelism with the testicular activity suggesting that thyroid hormone is essential for reproductive activity and related metabolic energy for avian species. Our data also suggest an inhibitory effect of melatonin on thyroid gland function [weight, thyroxine (T3/ T4) level and thymidine kinase activity, THK] both during active and inactive phases of the reproductive cycle. However, this inhibitory effect was less evident during the active phase. The low level of melatonin during the reproductively active phase might be due to long days of summer which prevented the birds from being hyperthyroidic. Therefore, we suggest that the level of melatonin serves as a physiological check to control the seasonal reproductive activities of gonads and thyroid which synergistically play most important physiological roles in energy metabolism of these seasonally breeding bird P. asiatica.

There is lack of basic information about peripheral melatonin level and its relationship with gestational hormones i.e., estrogens and progesterone, in human females. The present study addressed this issue and aimed to find the relationship between the levels of melatonin and estrogen and progesterone during different weeks of gestation, during parturition and during post-partum. The data suggest that there is a definite ratio of melatonin with both the steroids hormons before and during gestation as well as post-partum. An inverse relationship between the levels of estrogen and melatonin was observed in non-pregnant and post-partum women, while a direct relationship was observed during gestation. These two different types of hormonal relationships might be essential for maintenance of pregnancy. The inverse relationship of melatonin with progesterone during parturition may serve as a signal for parturition.

The significance of annual variation in metabolic (thyroxine) and chronobiotic (melatonin) hormones in relation to immune adaptation of the Indian palm squirrel was investigated. The squirrel is summer breeder and, hence, remains healthy during reproductively active phase (Feb - Aug) when melatonin level is low and thyroxine level is high. Our data show that the circulating levels of melatonin (MEL) and thyroxine (T4) have their respective annual rhythms, which are inversely related. Thyroxine level is low during the winter months (Sep-Jan) when metabolic activity of this rodent is also low. During this period melatonin level is high because of the short photoperiod and the squirrels indicate poor reproductive activity, with low gonadal steroids, which could be due to high circulating melatonin. The immune parameters also present an annual rhythmicity, which is parallel with circulating melatonin level, but inversely related to thyroxine level. This suggests that the metabolic hormone, thyroxine, and the chronobiotic hormone, melatonin, might be responsible for maintenance of the immune system to adapt the rodent for the rigors of the seasonal environmental changes.

The pineal gland, the transducer of several environmental cues through its hormone, melatonin, is known to play a critical role in the reproduction of several seasonally breeding mammals. The role of pineal gland in the control of male reproduction is already established beyond doubt. The logical hypothesis that the pineal gland would be involved in the aspects of female reproduction, particularly gestation, embryonic development and fetal growth, has been tested in a few seasonally breeding mammals and this paper reviews the outcome as of now. Evidence for establishment of an inverse relationship before pregnancy followed by moderately high activity with a positive correlation during pregnancy and a sudden increase in pineal activity during parturition has been produced, which suggests that high melatonin level has something to do with parturition or early abortion. The pineal gland perhaps maintains the normal physiology during gestation and post-parturition periods. This is further reflected in the prolactin levels of fetal sheep which is modulated by the photoperiod experienced by the mother during gestation. Maternal photoperiodic exposures during gestation and lactation periods alter the neonatal growth and sexual maturation of the Indian palm squirrel via the maternal transfer of photoperiodic information through the pineal gland, as aspect known as "pineal programming". The primary source of melatonin for the fetus is the maternal pineal gland, which is transferred across the placenta during conception and, later after parturition, through the milk, which suggests that a maternally generated melatonin rhythm would be expressed in fetal cerebrospinal fluid as well as in the circulation. Further, maternal melatonin is necessary for normal somatic growth and postnatal development of reproductive organs of the offspring. Melatonin ultimately affects reproductive activity by modulating hypothalamic neuroendocrine circuits whose activity is necessary for gonadal f

Endogenous melatonin is involved in regulation of reproductive function of the photoperiodic species. A circannual rhythmicity of the pineal gland in relation to reproduction has been observed in a tropical seasonally breeding mammal, Funambulus pennanti. A trade-off relation is known to exist between melatonin and the gonadal steroids. In vitro suppression of splenocyte proliferation by testosterone and the reversal of this effect by melatonin supplementation have already been reported. Melatonin receptors have been detected in the lymphoid tissues by binding of 2-[125I] iodomelatonin to splenocytes and thymocytes. We analyzed the presence of melatonin receptor adopting Western blot technique. We found that MTl receptor protein, one of the variants of melatonin receptor, is expressed in both the thymus and spleen tissue and the expression is suppressed by testosterone treatment. This substantiates the direct immunomodulatory role of melatonin. To find the significance of steroid toxicity at molecular level, particularly testosterone, it is important to study its effect on the expression pattern of these receptors.

Birds in general have not been frequently examined for the immunological influences of melatonin or pineal gland, as it has been potentially noted with the mammals including human being. There are only few reports suggesting that melatonin may play some role in the development and function of the immune system in the birds. The diurnal pattern of the melatonin synthesis is the same In almost all vertebrate groups so far examined, though differences exist in structure or anatomy of the pineal gland and seasonal variation in the peripheral melatonin level. Since functional relationship between neuroendocrine pineal gland and immune systems appears as to be diverse, it is logical that immunomodulatory effects of melatonin may be different in different seasons. The seasonal variation In melatonin level has been proved to improve the status of Immunity in seasonal tropical birds to bear the natural challenges. The level of peripheral melatonin minimizes some inflammatory diseases and sudden death syndrome in some poultry birds. The effect of melatonin also depends upon the phases of the inflammatory reaction/process. Pinealectomy in birds demonstrated functional interrelationship between the development of pineal gland, ontogeny of the melatonin secretion and immune system and/or neuroendocrine network. Bursectomy could influence the diurnal rhythm of melatonin and may abolish the effect of immunization on serum melatonin level. Specificities of avian immune system may be, however, very useful for understanding numerous phylogenetic and evolutionary mysteries. In this way a reciprocal functional connection between the avain immune system and the pineal gland seems to exist, but the mechanisms involved in maintaining the immune status by melatonin in avain group Is still not clear and needs to be elucidated.

Birds in general have not been frequently examined for the immunological influences of melatonin or pineal gland, as it has been potentially noted with the mammals including human being. There are only few reports suggesting that melatonin may play some role in the development and function of the immune system in the birds. The diurnal pattern of the melatonin synthesis is the same In almost all vertebrate groups so far examined, though differences exist in structure or anatomy of the pineal gland and seasonal variation in the peripheral melatonin level. Since functional relationship between neuroendocrine pineal gland and immune systems appears as to be diverse, it is logical that immunomodulatory effects of melatonin may be different in different seasons. The seasonal variation In melatonin level has been proved to improve the status of Immunity in seasonal tropical birds to bear the natural challenges. The level of peripheral melatonin minimizes some inflammatory diseases and sudden death syndrome in some poultry birds. The effect of melatonin also depends upon the phases of the inflammatory reaction/process. Pinealectomy in birds demonstrated functional interrelationship between the development of pineal gland, ontogeny of the melatonin secretion and immune system and/or neuroendocrine network. Bursectomy could influence the diurnal rhythm of melatonin and may abolish the effect of immunization on serum melatonin level. Specificities of avian immune system may be, however, very useful for understanding numerous phylogenetic and evolutionary mysteries. In this way a reciprocal functional connection between the avain immune system and the pineal gland seems to exist, but the mechanisms involved in maintaining the immune status by melatonin in avain group Is still not clear and needs to be elucidated.