Circannual Rhythm Research Articles

Photoperiodic Remodeling of Adiposity and Energy Metabolism in Non-Human Mammals.

Energy homeostasis and metabolism in mammals are strongly influenced by seasonal changes. Variations in photoperiod patterns drive adaptations in body weight and adiposity, reflecting changes in the regulation of food intake and energy expenditure. Humans also show distinct patterns of energy balance depending on the season, being more susceptible to gaining weight during a specific time of the year. Changes in body weight are mainly reflected by the adipose tissue, which is a key metabolic tissue and is highly affected by circannual rhythms. Mostly, in summer-like (long-active) photoperiod, adipocytes adopt a rather anabolic profile, more predisposed to store energy, while food intake increases and energy expenditure is reduced. These metabolic adaptations involve molecular modifications, some of which have been studied during the last years and are summarized in this review. In addition, there is a bidirectional relation between obesity and the seasonal responses, with obesity disrupting some of the seasonal responses observed in healthy mammals, and altered seasonality being highly associated with increased risk of developing obesity. This suggests that changes in photoperiod produce important metabolic alterations in healthy organisms. Biological rhythms impact the regulation of metabolism to different extents, some of which are already known, but further research is needed to fully understand the relationship between energy balance and seasonality.

Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study.

All parameters of human physiology show chronobiological variability. While circadian (cycle length~24h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length>24h) rhythms are largely unexplored. We investigated if cerebrovascular oxygen saturation (StO2) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity. Absolute StO2 and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7±3.6years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data. The GAM analysis revealed (i) a non-linear trend in the StO2 and [tHb] values over the 5-year span, (ii) a circannual (cycle length~12months) rhythm in StO2 at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2μM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length~6months) rhythm in [tHb] at the FL (A: 2.7μM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO2 (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure. We conclude that absolute values of StO2 and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO2 and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Seasonality of reproduction in Bathyergidae is a function of group size: A novel hypothesis (Rodentia)

In the African mole-rat family (Bathyergidae), species show both year-round and seasonal breeding patterns even though all species inhabit regions with varying seasonal rainfall patterns (a well-known selection driver of seasonal breeding). This short review suggests a novel hypothesis explaining why some African mole-rat species breed seasonally and others year-round. Namely, group-living African mole-rat species (with a mean colony size greater than five) exhibit an aseasonal reproduction pattern, as breeders, particularly females, possess year-round high body conditions. This is likely due to access to abundant and high-quality resources (food and water) throughout the year and reduced frequency of engaging in strenuous activities, such as digging, due to the increased efficiency of locating and retrieval of resource as a function of group size. While in the solitary and social species, with mean colony sizes of five or less, there are too few colony members to provide sufficient cooperative care benefits, the breeders show a seasonality to their body condition and thus breeding investment. As such, we hope to start a discussion on how group size could affect circannual breeding rhythms and propose some avenues for future research.

Seasonal variation in effect of anti-PD-1 initiation on overall survival among patients with advanced melanoma.

Melanoma is a highly immunogenic cancer, and circannual rhythms influence the activity of the immune system. We retrospectively collected information on all cases with metastatic melanoma (ocular melanoma excluded) that initiated treatment with BRAF-inhibitor-based therapy (BRAFi) or anti-PD-1 monotherapy (PD-1). Cases were divided in two groups based on treatment initiation in the summer half-year (April to September) or winter half-year (October to March). We collected a total of 1054 (BRAF-i) and 1205 (PD-1) patient cases. Median follow-up was 39.7 (BRAFi) and 47.5 (PD-1) months. We did not observe differences in outcomes across patients who were treated in summer versus winter in the BRAFi cohort. Furthermore, we did not observe significant differences in ORR, CRR, and PFS in the PD-1 cohort. However, in patients with BRAF wild-type disease of the PD-1 cohort, treatment initiation in summer was associated with an improved OS (mOS 39.7 months [summer] versus 21.3 months [winter]; HR 0.70, 95% CI 0.57-0.86, p=.0007). This result remained robust to multivariable proportional hazards adjustment (HR 0.70, 95% CI 0.57-0.87, p=.001). Initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma living in Denmark.

Temporal shifts in avian phenology across the circannual cycle in a rapidly changing climate: A global meta‐analysis

AbstractThe alteration of the timing of biological events is one of the best documented effects of climate change, with overwhelming evidence across taxa. Many studies have investigated the phenology of consumers, especially birds. However, most of these studies have focused on specific phenophases, whereas a global analysis of avian phenological trends during recent climate change across different phases of the circannual cycle is still lacking. Here, we performed a comprehensive meta‐analytic synthesis of the phenological responses (temporal shifts in days year−1) of birds across different phenophases (prebreeding migration, breeding, and postbreeding migration) by summarizing more than 5500 time series from 684 species from five continents during 1811–2018. Our results confirm that avian taxa have advanced prebreeding migration and breeding by ~2–3 days per decade, whereas no significant temporal changes in the timing of postbreeding migration were documented. Advancement in the timing of prebreeding migration and breeding strongly depended on migratory behavior, with the advance being the weakest for long‐distance migrants and the strongest for resident species. Diet generalists and primary consumers tended to advance prebreeding migration timing more than species with different dietary specializations. Increasing body size resulted in a larger advancement in the onset (but not in the mean date) of prebreeding migration and breeding, whereas phenological advances were larger in the northern than in the southern hemisphere. Our synthesis, covering most of the world, highlighted previously unappreciated patterns in avian phenological shifts over time, suggesting that specific life‐history or ecological traits may drive different responses to climate change.

Diapause in Univoltine and Semivoltine Life Cycles.

Although it is generally more adaptive for insects to produce additional generations than to have longer life cycles, some insects produce one or fewer generations per year (univoltine or semivoltine life cycles, respectively). Some insects with the potential to produce multiple generations per year produce a univoltine life cycle in response to environmental conditions. Obligatory univoltine insects have a single long diapause or multiple diapauses in different seasons. Semivoltine insects have multiple diapauses in different years, a prolonged diapause for more than a year, or diapause controlled by a circannual rhythm. Diapause in these insects greatly varies among species both in the physiological mechanism and in the evolutionary background, and there is no general rule defining it. In this review, we survey the physiological control of univoltine and semivoltine insects' diapause and discuss the adaptive significance of the long life cycles. Although constraints such as slow development are sometimes responsible for these life cycles, the benefits of these life cycles can be explained by bet-hedging in many cases. We also discuss the effect of climate warming on these life cycles as a future area of research.

Is Idiopathic Sudden Sensorineural Hearing Loss Seasonal?

To investigate the circannual rhythm (seasonal incidence) of idiopathic sudden sensorineural hearing loss (ISSNHL). Data were retrieved from the medical files of an original cohort of all consecutive patients with ISSNHL in a tertiary medical center between 2012 and 2020. A systematic literature search of "MEDLINE" via "PubMed," "Embase," and "Web of Science" on comparable published cases was performed. A Google Trends analysis of the term [sudden hearing loss] and related terms between 2014 and 2020 was also performed. Most of the published series (9/12) reported the highest ISSNHL incidence in the spring and the lowest in the winter (8/12). In our local series, the incidence during the winter was significantly lower than that for the other seasons by a factor of 0.69 (95% confidence interval, 0.65-0.77; p = 0.041; r = 0.36). Google Trends data showed no significant correlation between the calendric month and the incidence of ISSNHL in any of the analyzed countries ( p = 0.873, r2 = 0.029). The ISSNHL incidence was lowest during the winter season in our cohort and reported for other cohorts worldwide. Google Trends-based model analysis did not determine any circannual rhythm.

Influence of solar activity on water clusters. Annual variations 2015—2019

The variations of solar activity and distribution of solar energy due to the rotation of the Earth around its axis and around the Sun exert a strong influence on water clusters, as a result of which their chemical reactivity in hydrolytic processes can vary in a very wide range. This phenomenon is well manifested in the hydrolysis of the phosphoric acid esters. The 5-year regular investigations (2015—2019) of the hydrolysis of triethylphosphite in acetonitrile show that the rate of this reaction with all other conditions being equal displays diurnal, very large annual variations, and is also modulated by the 11-year cycles of solar activity. Since water is a necessary constituent in all forms of life, the discovered diurnal and annual variations of water clusters’ reactivity may underlie the biological circadian and circannual rhythms. The results obtained also point to the fact that the chemical reactivity of water clusters depends on the geographic latitude, and, in summer and winter, it can be significantly different at the same time in the Northern and Southern hemispheres. At the equator, where there should be no seasonal differences, measurements of the rate of triethylphosphite hydrolysis may become an independent method for assessing the solar activity.

Biological Rhythms, Disorders and their Energetic : A Review

Body rhythms are recurring molecular, hormonal, or psychological phenomena that occur in all living organisms. There are five types of body rhythms such as diurnal, circadian, ultradian, infradian, and circannual rhythms. The present review aims to discuss body rhythms, body rhythms disorders, and their energetics. Diurnal rhythms occur during the day and in resting, or inactivity at night, circadian rhythms complete one cycle in 24 hours and known as midday activity, ultradian are recurrent or repeated cycle in 24 hours, infradian rhythms complete one cycle more than one day, and circannual rhythms complete their cycle in 24 hours or one year. Body rhythms are following disorders like delayed sleep phase syndrome, altered Sleep, phase Shift Work Dysfunction, and circadian rhythm nap defects. Body rhythm control stress, lighten body load, exercise, avoid smoking, restrict sleeping, avoid napping during the day, provide energy for eating, and limit alcohol consumption. Body rhythms play an important role to regulate the body, while disturbance in body rhythms leads to several disorders.

Body Temperature Patterns and Energy Balance Hormones in Free-Living Thirteen-Lined Ground Squirrels (Ictidomys tridecemlineatus) from Different Latitudes.

AbstractThis article examines hormone concentrations and body temperature (Tb) patterns of free-living thirteen-lined ground squirrels (TLGSs) across the majority of their latitudinal range in the United States (from Texas to Minnesota). Free-living TLGSs () were implanted with Tbdata loggers in 2019 before they entered hibernation. Three adult female TLGSs, one each from Oklahoma (low latitude), Iowa (middle latitude), and Minnesota (high latitude), were recaptured in 2020 after the hibernation season. Although this provides an n of 1 for each location and therefore no statistically supported conclusions can be drawn, the hibernation season was longest in the animal from the highest latitude with coldest winter soil temperatures (Minnesota) and shortest in the animal retrapped at the lowest latitude (Oklahoma). Torpor bouts were generally longer when soil temperatures were lower. The Iowa and Minnesota squirrels had a prolonged period of short torpor bouts with Tb near 20°C at the beginning of the hibernation season. Concentrations of the orexigenic hormone ghrelin and the sex hormones estradiol and testosterone were also compared in populations from different latitudes. In general, Minnesota males had higher testosterone than males from other populations, possibly due to a later breeding season relative to other squirrel populations. Animals trapped in early summer had significantly lower concentrations of ghrelin than those captured in midsummer, potentially driving the fat-storing period before the hibernation season. Together, these results suggest latitudinal variation in physiological regulation of circannual rhythms.

Grape-Seed Procyanidin Extract (GSPE) Seasonal-Dependent Modulation of Glucose and Lipid Metabolism in the Liver of Healthy F344 Rats.

Seasonality is gaining attention in the modulation of some physiological and metabolic functions in mammals. Furthermore, the consumption of natural compounds, such as GSPE, is steadily increasing. Consequently, in order to study the interaction of seasonal variations in day length over natural compounds’ molecular effects, we carried out an animal study using photo-sensitive rats which were chronically exposed for 9 weeks to three photoperiods (L6, L18, and L12) in order to mimic the day length of different seasons (winter/summer/and autumn-spring). In parallel, animals were also treated either with GSPE 25 (mg/kg) or vehicle (VH) for 4 weeks. Interestingly, a seasonal-dependent GSPE modulation on the hepatic glucose and lipid metabolism was observed. For example, some metabolic genes from the liver (SREBP-1c, Gk, Acacα) changed their expression due to seasonality. Furthermore, the metabolomic results also indicated a seasonal influence on the GSPE effects associated with glucose-6-phosphate, D-glucose, and D-ribose, among others. These differential effects, which were also reflected in some plasmatic parameters (i.e., glucose and triglycerides) and hormones (corticosterone and melatonin), were also associated with significant changes in the expression of several hepatic circadian clock genes (Bmal1, Cry1, and Nr1d1) and ER stress genes (Atf6, Grp78, and Chop). Our results point out the importance of circannual rhythms in regulating metabolic homeostasis and suggest that seasonal variations (long or short photoperiods) affect hepatic metabolism in rats. Furthermore, they suggest that procyanidin consumption could be useful for the modulation of the photoperiod-dependent changes on glucose and lipid metabolism, whose alterations could be related to metabolic diseases (e.g., diabetes, obesity, and cardiovascular disease). Furthermore, even though the GSPE effect is not restricted to a specific photoperiod, our results suggest a more significant effect in the L18 condition.

Seasonal changes of internet searching suggest circannual rhythmicity of primary headache disorders.

To investigate whether web searching for headache disorders presents some circannual rhythm. Studies support the influence of seasonal rhythms in primary headache disorders such as cluster headache (CH) and episodic migraine. We investigated whether internet users' searching for headaches reflect these circannual rhythms. This was an internet-based study using the Google Trends (Google) platform. The 10-year interest across four related topics (headache, migraine, tension-type headache [TTH], and CH) in 31 European countries was scanned. Significant differences between months were found for the topics "headache" and "migraine." Interest in the former was superior in February (median for all countries, 61 [25th-75th percentile, 45-80]), October (61 [44-75]), and November (61 [45-76]). The lowest search volumes for headache appeared in July (52 [37-66]) (p<0.001). Migraine was searched most commonly in November (56 [40-73]) and rarely in June (46.5 [31-64]) (p<0.001). Differences were observed for the topic of headache in Northern Europe (p=0.001) and for headache and migraine in Central Europe (p<0.001 and p=0.016 respectively) but not in the southern region. TTH and CH were apparently less searched and no evident trends regarding them were present (median, 22 [0-44] for TTH and 15 [0-33] for CH; direct popularity comparison: headache 56 [44-63], migraine 16 [12-24], TTH 2 [1-2], and CH 2 [1-2]; between-month differences, p=0.168 and p=0.081 respectively). Public attention on headache-related topics on the internet is distributed according to a significant trend of increased searching around spring and autumn. It suggests that a large number of patients may experience some level of seasonal variation in their headaches. Assessment of whether those temporal changes are present in clinical practice is necessary.

Peripheral circadian gene activity is altered during hibernation in the thirteen-lined ground squirrel

Many small mammals living in seasonally cold environments rely on hibernation, utilizing strong metabolic rate suppression and a slow consumption of adipose reserves to survive the winter months. The circannual rhythm of hibernation is well known but less is known about the role of the circadian clock while animals are in torpor for weeks at a time. We hypothesized that due to strong global suppression of transcription and translation in the torpid state, that circadian clock activity would likewise be suppressed in peripheral tissues during hibernation. However, the present study indicates that peripheral circadian clock activity persists during torpor. Using 13-lined ground squirrels (Ictidomys tridecemlineatus) as the model, this study analyzed transcript and protein responses by clock components, comparing euthermic control animals with squirrels in deep torpor for >3 days (subcutaneous body temperature 5–8 °C). The data show tissue specific responses by mRNA transcript levels: (a) no significant changes in transcript abundance in liver of control versus torpid squirrels, (b) a strong increase in Nr1d1 levels in white adipose during torpor, and (c) five significant transcript changes in skeletal muscle during torpor (increased Bmal1, Clock, Cry1 and Nr1d1 but decreased Per1). Levels of core clock proteins (BMAL1, CRY2, PER2, and casein kinases CK1δ and CK1ε) were also assessed across five time points of the torpor/arousal cycle showing both tissue- and time-dependent changes in clock proteins that were most prominent in liver and white adipose and indicating that peripheral clocks are still active in tissues over the torpor/arousal cycle.

Trastorno por Déficit de Atención con Hiperactividad: Ritmo Circanual en el Mes de Nacimiento

Attention Deficit Hyperactivity Disorder: Circannual Rhythm in the Month of Birth. We studied the existence of circanual rhythm in the month of birth in participants with attention deficit hyperactivity disorder (ADHD) and analyzed the association between months of birth and ADHD. We analyzed 10,978 participants (1,778 ADHD/9,200 non-ADHD), aged 3 to 18 years. A consecutive sample of first visits to mental health between 1992 and 2021 is used. Participants with ADHD exhibit a significant circannual rhythm in the months of birth, with an acrophase in October. Being born in the last quarter of the year significantly increases the probability of being diagnosed with ADHD, controlling for the effect of sex and age. As the months of the year go by, there is a significant increasing linear trend of being diagnosed with ADHD, which is not observed neither in general population nor in cases without ADHD. Caution is necessary in diagnosis and treatment of children born in the last months of year, who, due to their greater immaturity compared to the other children in class, could be misdiagnosed and treated as ADHD.

Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals.

BackgroundThe study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of pleiotropic genes is involved in the synthesis (AANAT, ASMT) and signaling (MTNR1A, MTNR1B) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin.MethodsWe examined AANAT, ASMT, MTNR1A and MTNR1B in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact.ResultsWe report that crocodylians retain intact melatonin genes and express AANAT and ASMT in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes.ConclusionsThe losses of melatonin synthesis and signaling date to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species.

Seasonality and climatic control of reproduction in wild-caught female Lesser Egyptian jerboa (Jaculus jaculus) from central Saudi Arabia

In arid regions, unpredictable rainfall patterns and extreme temperature variation occurs; this poses severe constraints on reproduction in small mammals. In the present study, the gonad morphometrics, gonadal histology and endocrine profiles of the female Lesser Egyptian jerboas (Jaculus jaculus) were studied over one year in a wild population from central Saudi Arabia. An unusual rainfall pattern occurred during this study period, with three out of four seasons receiving rainfall. Pregnant females were observed during every season when rainfall fell. Yet, a distinct reproduction pattern was also observed in the reproductive parameters of J. jaculus, likely entrained by ambient temperature and photoperiodic changes, with indicators of reproductive activity being at its highest during the winter months. Jaculus jaculus, appear to possess an endogenous circannual rhythm (seasonality) of breeding, entrained by ambient temperature and photoperiod. However, they have a plasticity to their breeding strategy, which allows them to breed opportunistically. As global warming takes effect, many species which currently inhabit temperate regions may experience desertification. Understanding how species that inhabit deserts today are adapted to these harsh conditions may allow researchers to identify temperate species that are more at risk to climatic changes due to global warming.

Revelation of candidate genes and molecular mechanism of reproductive seasonality in female rohu (Labeo rohita Ham.) by RNA sequencing

BackgroundCarp fish, rohu (Labeo rohita Ham.) is important freshwater aquaculture species of South-East Asia having seasonal reproductive rhythm. There is no holistic study at transcriptome level revealing key candidate genes involved in such circannual rhythm regulated by biological clock genes (BCGs). Seasonality manifestation has two contrasting phases of reproduction, i.e., post-spawning resting and initiation of gonadal activity appropriate for revealing the associated candidate genes. It can be deciphered by RNA sequencing of tissues involved in BPGL (Brain-Pituitary-Gonad-Liver) axis controlling seasonality. How far such BCGs of this fish are evolutionarily conserved across different phyla is unknown. Such study can be of further use to enhance fish productivity as seasonality restricts seed production beyond monsoon season.ResultA total of ~ 150 Gb of transcriptomic data of four tissues viz., BPGL were generated using Illumina TruSeq. De-novo assembled BPGL tissues revealed 75,554 differentially expressed transcripts, 115,534 SSRs, 65,584 SNPs, 514 pathways, 5379 transcription factors, 187 mature miRNA which regulates candidate genes represented by 1576 differentially expressed transcripts are available in the form of web-genomic resources. Findings were validated by qPCR. This is the first report in carp fish having 32 BCGs, found widely conserved in fish, amphibian, reptile, birds, prototheria, marsupials and placental mammals. This is due to universal mechanism of rhythmicity in response to environment and earth rotation having adaptive and reproductive significance.ConclusionThis study elucidates evolutionary conserved mechanism of photo-periodism sensing, neuroendocrine secretion, metabolism and yolk synthesis in liver, gonadal maturation, muscular growth with sensory and auditory perception in this fish. Study reveals fish as a good model for research on biological clock besides its relevance in reproductive efficiency enhancement.

Seminal Vesicles and Bulbourethral Glands of Mammals: Morphology, Physiology, Ecology, Action of Extreme Destabilizing Factors

In mammals, the adnexal sex glands are represented by seminal vesicles, the prostate gland, urethral and bulbourethral glands, as well as glands that coagulate sperm and ampullary glands. The secret of the accessory genital glands increases the volume of the ejaculate (the share of secretions of these glands accounts for about 95% of the volume of ejaculate) promotes sperm, causes increased contraction of smooth muscle cells in the walls of the female genital tract.The purpose of this review is to analyze the morphofunctional organization of seminal vesicles and bulbourethral glands of mammalian animals and humans.The presence or absence of seminal vesicles is a species-specific feature. Among mammals, seminal vesicles are well developed in some rodents, insectivores, a number of domestic animals (cattle, pigs), and primates. These glands are absent in cloacae, marsupials, some carnivores, a number of insectivores, artiodactyls. Bulbourethral glands are well developed in rodents, bats, primates, and some ungulates.In the wall of the seminal vesicles, the mucous, muscular and outer membranes are isolated. The epithelium of the secretory parts is pseudomultitial, the interstitium is represented by loose fibrous connective tissue and a significant number of smooth muscle cells. In the wall of the bulbourethral glands, the mucosa and adventitial membrane are isolated. The secretory end sections of the bulbourethral glands are lined with a single-layer single-row epithelium, glandular cells produce a mucosal or mixed secret. The seminal vesicles and bulbourethral glands are androgen-dependent glands. In species with a seasonal pattern of reproduction, their morphofunctional characteristics undergo significant changes during the circannual rhythm of reproduction.The epithelium of seminal vesicles and bulbourethral glands is very sensitive to the action of various adverse factors (heavy metal compounds, organic xenobiotics, electromagnetic radiation, ultrasound, etc.). When exposed to various negative factors in the adnexal glands, a complex of changes occurs (edema of connective tissue and epithelium, decreased secretory activity of epithelial cells, desynchronization of the secretory cycle, desquamation of glandular epithelial cells, proliferation of interstitial connective tissue).There is a lack of information on many aspects of the characteristics of the adnexal glands of the male reproductive system, primarily on the morphology and physiology of the adnexal glands of animals in natural ecosystems, on the ultrastructural and immunohistochemical characteristics of these glands, as well as on the mechanisms of regulation of morphofunctional rearrangements of the adnexal glands during seasonal reproduction rhythms, in the conditions of adaptation to various negative influences.

Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals

Background: The study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of genes is involved in the synthesis (AANAT, ASMT) and signaling (MTNR1A, MTNR1B) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin. Methods: We examined AANAT, ASMT, MTNR1A and MTNR1B in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact. Results: We report that crocodylians retain intact melatonin genes and express AANAT and ASMT in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes. Conclusions: The losses of melatonin synthesis and signaling dates to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species.

Influence of Seasonal Vitamin D Changes on Clinical Manifestations of Rheumatoid Arthritis and Systemic Sclerosis.

Vitamin D [1,25(OH)2D—calcitriol] is basically a steroid hormone with pleiotropic biologic effects, and its impact on the regulation of immune system may influence several clinical conditions. Calcidiol (25OHD), as precursor of calcitriol, derives, for the most part (80%), from cutaneous cholesterol (7-dehydrocholesterol) under the action of UV-B (sunlight). Consequently, serum concentrations fluctuate during the year following the circannual rhythm of sun exposition. We will update about the available evidence regarding the complex influence of seasonal vitamin D changes on two different chronic connective tissue diseases, namely rheumatoid arthritis (RA) and systemic sclerosis (SSc). Notably, RA is an emblematic model of autoimmune disease with prevalent joint inflammatory features, while SSc is mainly an autoimmune progressive pro-fibrotic disease. However, in both conditions, low serum concentrations of 25OHD are involved in the pathogenesis of the diseases, and emerging data report their impact on clinical manifestations.