Unconditional versus condition-dependent social immunity.

Socially living animals can counteract disease through cooperative defences, leading to social immunity that collectively exceeds the sum of individual defences. In superorganismal colonies of social insects with permanent caste separation between reproductive queen(s) and nonreproducing workers, workers are obligate altruists and thus engage in unconditional social immunity, including highly specialised and self-sacrificial hygiene behaviours. Contrastingly, cooperation is facultative in cooperatively breeding families, where all members are reproductively totipotent but offspring transiently forgo reproduction to help their parents rear more siblings. Here, helpers should either express condition-dependent social immunity or disperse to pursue independent reproduction. We advocate inclusive fitness theory as a framework to predict when and how indirect fitness gains may outweigh direct fitness costs, thus favouring conditional social immunity.

A systematic review of predictive, diagnostic, and prognostic biomarkers for detecting reproductive diseases in cattle using traditional and omics approaches.

Reproductive diseases and illnesses pose significant challenges in cattle farming, affecting fertility, milk production, and overall herd health. In recent years, the integration of various omics approaches, including transcriptomics, proteomics, metagenomics, miRNAomics, and metabolomics, has revolutionized the study of these conditions. This systematic review summarised the findings from studies that investigated reproductive disease biomarkers in both male and female cattle. After extracting 6137 studies according to exclusion and inclusion criteria, a total of 60 studies were included in this review. All studies identified were associated with female cattle and none were related to reproductive diseases in bulls. The analysis highlights specific biomarkers, metabolic pathways, and microbial compositions associated with bovine reproductive disease conditions, providing valuable insights into the underlying molecular mechanisms of disease. Pro-inflammatory cytokines such as IL-1ß, IL-8, IL-4, IL-6, TNFα and acute-phase response proteins such as SAA and HP have been identified as promising biomarkers for bovine reproductive diseases. However, further research is needed to validate these markers clinically and to explore potential strategies for improving cow reproductive health. The role of bulls as carriers of venereal diseases has been underestimated in the current literature and therefore needs more attention to understand their impact on infectious reproductive diseases of female cattle.

The phytoplankton community affects the energy metabolism and immunomodulation strategy of oyster during breeding seasons.

The mass mortality of Pacific oyster Crassostrea gigas has become a severe ecological and economic concern to Chinese aquaculture, which is proposed to be linked to the phytoplankton community in the farming waters. In the present study, both field and laboratory experiments were conducted to identify the phytoplankton taxa associated with oyster mortality and explore the molecular mechanism by which they affect the physiological health of oysters. The field experiment showed that more serious mortality of oysters was observed in the North Yellow Sea from July to September in 2018 (average survival rate of 75.11 %) than in 2019 (average survival rate of 85.78 %), with the proportion of Bacillariophyta (diatoms) in the phytoplankton community in 2018 lower than that in 2019. In comparison to 2019, reduced dry weight, lower glycogen and triglyceride contents in hepatopancreas, lower 17ß-estradiol and testosterone concentrations in gonad, as well as a generally weaker immune response against Vibrio splendidus stimulation were detected in the oysters sampled in 2018. The treatment of oysters with either starvation (starvation group) or Nitzschia closterium f. minutissima feeding (N. closterium group) was conducted to verify the field findings, with individuals reared in natural seawater as control. After 40 days of N. closterium feeding, dry weight, glycogen and triglyceride contents in hepatopancreas significantly increased, as well as the biosynthesis of sex hormones and gonadal maturation were promoted compared to the control and starvation groups. Moreover, a much stronger immune response against V. splendidus stimulation was observed in the oysters of N. closterium group, with the fold-changes of norepinephrine content in serum, SOD activity in hepatopancreas, and the mRNA expression level of IL17-5 and HSP70 in haemocytes higher than those in the control and starvation groups. Collectively, these results suggested that lack of diatoms in the farming waters suppressed the energy storage and gonadal maturation of adult oysters, and also resulted in a compromised immune response against bacterial infection, which may be a leading cause of the mass mortality of oysters living in diatom-deficient waters during breeding seasons.

Trematode Diplostomum pseudospathaceum inducing differential immune gene expression in sexual and gynogenetic gibel carp (Carassius gibelio): parasites facilitating the coexistence of two reproductive forms of the invasive species.

Introduction: Parasite-mediated selection is considered one of the potential mechanisms contributing to the coexistence of asexual-sexual complexes. Gibel carp (Carassius gibelio), an invasive fish species in Europe, often forms populations composed of gynogenetic and sexual specimens. Methods: The experimental infection was induced in gynogenetic and sexual gibel carp using eye-fluke Diplostomum pseudospathaceum (Trematoda), and the transcriptome profile of the spleen as a major immune organ in fish was analyzed to reveal the differentially expressed immunity-associated genes related to D. pseudospathaceum infection differing between gynogenetic and sexual gibel carp. Results: High parasite infection was found in gynogenetic fish when compared to genetically diverse sexuals. Although metacercariae of D. pseudospathaceum are situated in an immune-privileged organ, our results show that eye trematodes may induce a host immune response. We found differential gene expression induced by eye-fluke infection, with various impacts on gynogenetic and sexual hosts, documenting for the majority of DEGs upregulation in sexuals, and downregulation in asexuals. Differences in gene regulation between gynogenetic and sexual gibel carp were evidenced in many immunity-associated genes. GO analyses revealed the importance of genes assigned to the GO terms: immune function, the Notch signaling pathway, MAP kinase tyrosine/threonine/phosphatase activity, and chemokine receptor activity. KEGG analyses revealed the importance of the genes involved in 12 immunity-associated pathways - specifically, FoxO signaling, adipocytokine signaling, TGF-beta signaling, apoptosis, Notch signaling, C-type lectin receptor signaling, efferocytosis, intestinal immune network for IgA production, insulin signaling, virion - human immunodeficiency virus, Toll-like receptor signaling, and phosphatidylinositol signaling system. Discussion: Our study indicates the limited potential of asexual fish to cope with higher parasite infection (likely a loss of capacity to induce an effective immune response) and highlights the important role of molecular mechanisms associated with immunity for the coexistence of gynogenetic and sexual gibel carp, potentially contributing to its invasiveness.

Impact of repeated ovarian hyperstimulation on the reproductive function.

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Reproductive Immunology and Pregnancy 2.0.

This Special Issue comprises original articles in the field of clinical studies whose major topics concern the genetic and immunological aspects of miscarriage and pre-eclampsia, the isolation of decidua macrophages and Hofbauer cells in the placenta for diagnostic purposes, and epigenetic mechanisms that trigger labor [...].

Regulation of the innate immune cells during pregnancy: An immune checkpoint perspective.

The foetus can be regarded as a half-allograft implanted into the maternal body. In a successful pregnancy, the mother does not reject the foetus because of the immune tolerance mechanism at the maternal-foetal interface. The innate immune cells are a large part of the decidual leukocytes contributing significantly to a successful pregnancy. Although the contributions have been recognized, their role in human pregnancy has not been completely elucidated. Additionally, the accumulated evidence demonstrates that the immune checkpoint molecules expressed on the immune cells are co-inhibitory receptors regulating their activation and biological function. Therefore, it is critical to understand the immune microenvironment and explore the function of the innate immune cells during pregnancy. This review summarizes the classic immune checkpoints such as PD-1, CTLA-4 and some novel molecules recently identified, including TIM-3, CD200, TIGIT and the Siglecs family on the decidual and peripheral innate immune cells during pregnancy. Furthermore, it emphasizes the role of the immune checkpoint molecules in pregnancy-associated complications and reproductive immunotherapy.

NK cells that differ in expression of NKp46 might play different roles in endometrium.

NKp46 is a natural cytotoxicity receptor expressed by NK cells and its expression is decreased in reproductive failure patients. NKp46 can be subdivided into NKp46dim and NKp46bright according to different fluorescence staining intensities. We investigated the role of the NKp46 receptor in determining the reproductive outcomes. Uterine endometrium was collected from 34 women with reproductive failure and divided into the pregnant and failed groups based on the results of a pregnancy reaction test during a 1-year follow-up period. NKp46 receptor and other activating or inhibitory receptors expressed on NK cells as well as intracellular cytokine production by NK cells were analyzed by multicolor flow cytometry. In the failed group, the percentage of NKp46dim NK cells (P < 0.05) was significantly higher and percentages of NKp46bright NK cells (P < 0.01) and CD16-/CD56bright NK cells (P < 0.05) were significantly lower than those in the pregnant group. NKp46dim NK cells were significantly and positively correlated with CD16+/NKp46dim NK cells; NKp46bright NK cells were significantly and positively correlated with CD16-/NKp46bright NK cells. CD16+/NKp46dim NK cells were significantly and positively correlated with IFN-γ- and/or TNF-α-producing NK cells; CD16-/NKp46bright NK cells were significantly and positively correlated with TGF-ß1-producing NK cells. We suggest that the NKp46 receptor plays different roles in reproduction based on the different fluorescence intensities associated with NK cells, i.e. NKp46dim NK cells are involved in killing cells, whereas NKp46bright NK cells are involved in cytokine production, indicating that NKp46 could be a predictive marker to see a tolerate condition for embryos.

Effects of SARS-CoV-2 infection on human reproduction.

The worldwide infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts human health and life on multiple levels. People infected with SARS-CoV-2 suffer from physical disorders and psychological distress. At present, no direct evidence indicates that SARS-CoV-2 negatively influences human reproduction, and the possibility that gametes and embryos are affected requires further investigation. To evaluate the potential effects of SARS-CoV-2 infection on human reproduction and fetal health, this review summarizes the basic and clinical research of SARS-CoV-2 on reproduction up to date, hoping to offer guidance and advice to people at reproductive age and provide clues for the prevention and treatment of associated diseases.

Ovarian morphometrical evaluation to assess reproductive activity suppression in heavy weight finishing gilts immunized against gonadotropin-releasing hormone.

It is known that immunizing gilts against gonadotropin-releasing hormone (GnRH) is an efficient castration method that increases their growth performance. However, it is still unknown the ovarian histophysiology outcomes after this procedure. Therefore, the aim of this study was to investigate in detail, using morphological and morphometrical methods, changes in the ovarian structure that result in the suppression of ovarian activity, as well as to gain knowledge on the ovarian structure to assist in ovarian histopathological diagnoses. Seventy-two pre-pubertal finishing gilts were allocated to two experimental groups: immunized (IC; n = 36; gilts which received two injections of 2 mL of Vivax® - one at 15 and another at 19 weeks of age) and control (CT; n = 36, females which received two saline injections following the same protocol). All gilts were euthanized at 25 weeks of age and the ovaries of 5 gilts from each experimental group collected for biometrical and histomorphometrical analysis. IC gilts showed higher body weights, but smaller ovaries compared to CT females. In addition, the number of small follicles (≤ 2 mm) on the ovarian surface was higher, while no large follicles (> 6 mm) nor corpora lutea were found in the ovaries of IC gilts. Histomorphometrical analysis revealed that IC females showed higher numbers of quiescent and active primordial, primary, pre-antral and final stage atretic follicles. Moreover, follicle size, antrum diameter and area of the granulosa layer from mature follicles were smaller in IC gilts. Collectively, these results demonstrate that the efficacy of immunization against GnRH is related to the blockage of follicular recruitment and selection, thus suppressing reproductive activity in finishing gilts.

Identifications of immune-responsive genes for adaptative traits by comparative transcriptome analysis of spleen tissue from Kazakh and Suffolk sheep.

Aridity and heat are significant environmental stressors that affect sheep adaptation and adaptability, thus influencing immunity, growth, reproduction, production performance, and profitability. The aim of this study was to profile mRNA expression levels in the spleen of indigenous Kazakh sheep breed for comparative analysis with the exotic Suffolk breed. Spleen histomorphology was observed in indigenous Kazakh sheep and exotic Suffolk sheep raised in Xinjiang China. Transcriptome sequencing of spleen tissue from the two breeds were performed via Illumina high-throughput sequencing technology and validated by RT-qPCR. Blood cytokine and IgG levels differed between the two breeds and IgG and IL-1ß were significantly higher in Kazakh sheep than in Suffolk sheep (p < 0.05), though spleen tissue morphology was the same. A total of 52.04 Gb clean reads were obtained and the clean reads were assembled into 67,271 unigenes using bioinformatics analysis. Profiling analysis of differential gene expression showed that 1158 differentially expressed genes were found when comparing Suffolk with Kazakh sheep, including 246 up-regulated genes and 912 down-regulated genes. Utilizing gene ontology annotation and pathway analysis, 21 immune- responsive genes were identified as spleen-specific genes associated with adaptive traits and were significantly enriched in hematopoietic cell lineage, natural killer cell-mediated cytotoxicity, complement and coagulation cascades, and in the intestinal immune network for IgA production. Four pathways and up-regulated genes associated with immune responses in indigenous sheep played indispensable and promoting roles in arid and hot environments. Overall, this study provides valuable transcriptome data on the immunological mechanisms related to adaptive traits in indigenous and exotic sheep and offers a foundation for research into adaptive evolution.

The intersection of stress, sex and immunity in fishes.

While sexual dimorphism in immune responses has been documented in other vertebrates, evidence for a similar phenomenon in fish is lacking. Here, we review the relationship between immunity, stress, spawning, and sex hormones in fish to gain a better understanding of sex-based differences in fish immune responses and its consequences for aquaculture. It is well known that there is a strong link between the stress response and immune function in fish. In addition, research to date has demonstrated that sexual dimorphism in the stress response exists in many species; yet, the relationship between the sexual dimorphic stress responses and immune function has rarely been explored together. Aside from stress, spawning is also known to trigger changes in fish immune responses. Estrogens and androgens have been shown to modulate the immune system which could account for differences between the two sexes of fish when spawning; however, evidence regarding the sexual dimorphism of these changes varies between fishes and is likely related to the spawning strategy employed by a given species. Sex hormones are also used in aquaculture practices to produce monosex populations, and exposure to these hormones early in development has been shown to impact the development of immune organs in several fishes. While female fish are generally thought to be more robust than males, aquaculture practices should also consider the role that maternal stress has on the immune function of the offspring and what role this plays in compromising the immune response of farmed fish.

Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles.

Since 1978, in the first decades of in vitro fertilization (IVF), the use of ovarian hyperstimulation allowed for the development and transfer of multiple embryos. As IVF technology improved, the number of multiple pregnancies increased, which led to gradual reduction in the number of embryos that were transferred. Embryo freezing (vitrification) was recommended to allow subsequent transfer if the fresh cycle was unsuccessful. However, experimentation has continued to improve pregnancy outcomes. We discuss here the significance of frozen embryo transfer cycle and the impact of uterine and peripheral immunity dominated by NK cells and regulatory T cells and human chorionic gonadotropin on pregnancy outcome in this innovative mode of IVF therapy.

Natural killer cells and reproductive success.

Natural killer (NK) cell assessment has been attempted since the 1990s and, apart from antibody testing, is probably the commonest immune test available to clinicians. It is clear that simple enumeration of uterine NK cells by immunohistochemistry is inadequate, although better methodology such as flow cytometry may prove to be more beneficial in the future. Blood testing is an appealing noninvasive test that may be a marker for immune dysfunction, rather than a guide to uterine numbers per se. It is currently performed in women with repeated reproductive failure and should be done using tests of activation. Patients value investigation and clinicians should prefer it to blind empirical immune therapy in repeated reproductive failure cases. But, in addition to blood NK testing, a fundamental new NK genetic test (the KIR/HLA-C interaction) is likely to provide an even more effective diagnostic tool. Insights from KIR/HLA-C analysis imply that new immune therapy trials will need to take KIR/HLA-C results into account.

Role of Kisspeptin in Regulation of Reproductive and Immune Reactions.

The work is focused on physiological role of the hormone kisspeptin produced by neurons of the hypothalamus anterior zone, which is a key regulator of reproduction processes. Role of the hormone in transmission of information on metabolic activity and induction of the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus that determines gestation processes involving fertilization, placentation, fetal development, and child birth is considered. The literature data on molecular mechanisms and effects of kisspeptin on reproductive system including puberty initiation are summarized and analyzed. In addition, attention is paid to hormone-mediated changes in the cardiovascular system in pregnant women. For the first time, the review examines the effect of kisspeptin on functional activity of immune system cells presenting molecular mechanisms of the hormone signal transduction on the level of lymphoid cells that lead to the immune tolerance induction. In conclusion, a conceptual model is presented that determines the role of kisspeptin as an integrator of reproductive and immune functions during pregnancy.

Photoperiodic manipulation modulates the innate and cell mediated immune functions in the fresh water snake, Natrix piscator.

Objectives of the current work were to investigate the role of photoperiod and melatonin in the alteration of immune responses in a reptilian species. Animals were kept on a regimen of short or long days. Blood was obtained and leucocytes were isolated to study various innate immune responses. Lymphocytes were separated from blood by density gradient centrifugation and were used to study proliferation. Respiratory burst activity was measured through nitrobluetetrazolium reduction assay while nitric oxide production by leucocytes was assayed by nitrite assay. Lymphocytes were isolated and used to study proliferation with and without B and T cell mitogens. Photoperiodic manipulation acted differentially on leucocyte counts. Nitrite release was increased while superoxide production was decreased in cultures obtained from the snakes kept on the short day regimen. Significant enhancement of mitogen induced lymphocyte proliferation was observed in cultures from the animals kept in either long or short days compared to cultures from the animals kept in natural ambient day length. Use of in vitro melatonin showed that lymphocytes from the animals, kept in long days, were more reactive. Photoperiod induces changes in immune status which may permit adaptive functional responses in order to maintain seasonal energetic budgets of the animals. Physiological responses (like elevated immune status) are energetically expensive, therefore, animals have evolved a strategy to reduce immune functions at times when energy is invested in reproductive activities. Natrix piscator breeds from September to December and elevated pineal hormone in winter suppresses reproduction while immunity is stimulated.

The immunogenetics of sexual parasitism.

Sexual parasitism has evolved as a distinctive mode of reproduction among deep-sea anglerfishes. The permanent attachment of males to host females observed in these species represents a form of anatomical joining, which is otherwise unknown in nature. Pronounced modifications to immune facilities are associated with this reproductive trait. The genomes of species with temporarily attaching males lack functional aicda genes that underpin affinity maturation of antibodies. Permanent attachment is associated with additional alterations, culminating in the loss of functional rag genes in some species, abolishing somatic diversification of antigen receptor genes, the hallmark of canonical adaptive immunity. In anglerfishes, coevolution of innate and adaptive immunity has been disentangled, implying that an alternative form of immunity supported the emergence of this evolutionarily successful group of vertebrates.