In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

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From inflammation to sickness and depression: when the immune system subjugates the brain

http://www.smhc.org.cn/uploadfiles/2014/09/20140929090442442.pdf

A Meta-Analysis of Cytokines in Major Depression

http://dcawatch.com/wp-content/uploads/2012/06/pdf-of-original-paper-on-DCA-submitted-to-the-publication-Cancer-Cell2.pdf

A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth

Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclinical tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonised control animals. Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonisation of the GF animals post weaning is insufficient to reverse the CNS neurochemical consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addition, reduced anxiety in GF animals is also normalised following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochemical, but not behavioural, profile is resistant to restoration of a normal gut flora in later life.

The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner

The aryl hydrocarbon receptor (AHR) has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3 + regulatory T cells (Tregs) versus Th17 cells. In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent Treg generation. We additionally investigate the dependence of TGF-β on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells postexposure to TGF-β. These results shed light on the relationship of IDO to the generation of Tregs, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.

An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells

Intracytoplasmic morphologically selected sperm injection (IMSI) is now a reality in ART practice but still with a lot of questions regarding (1) the terminology of vacuoles, their classification, their location on the sperm head, and their origin and meaning; (2) the application of IMSI instead of in vitro fertilization in cases of unexplained infertility; (3) the age of the woman; and (4) the technical aspects. We have to be aware that this technique is demanding and has to be performed in the best working conditions so as not to impair the oocyte quality. The introduction of IMSI has the advantage that embryologists realize that more attention has to be paid during sperm selection even in case of classical intracytoplasmic sperm injection (ICSI). The application of IMSI leads to more and better quality blastocysts and, as consequence, it increases the chances of selecting the proper embryo for transfer with high implantation potential. Even though there is no real proof in the human species on the abnormal outcome generated by spermatozoa carrying vacuoles, a higher and better-resolution technique has to be added as an additional tool for ICSI knowing the possible consequence of sperm DNA damage for offsprings.

Intracytoplasmic Morphologically Selected Sperm Injection

Research question What are the main risk factors associated with ectopic pregnancy and what is the true incidence of ectopic pregnancies in an IVF programme? Design Retrospective single-centre study of 12,429 blastocyst transfers (8182 fresh and 4247 frozen embryo transfers) conducted between January 2010 and December 2017. IVF outcome was analysed, and ectopic pregnancy risk evaluated according to patient's characteristics and assisted reproductive technology treatment factors. Results Of 5061 patients reporting a positive pregnancy test, 43 were diagnosed with ectopic pregnancy (0.85%). Neither female age (36.7 versus 35.8 years), body mass index, quality of transfer nor stimulation protocol affected the ectopic pregnancy rate, but history of previous ectopic pregnancy (OR 3.26; P = 0.0080), tubal surgery, or both (OR 6.20; P Conclusions Unfavourable uterine environment, including uterine pathologies, uterine or tubal surgery and suboptimal endometrial build-up were related to ectopic pregnancy. Low expansion grade of blastocysts was identified as an additional putative risk factor for ectopic pregnancy, indicating the importance of proper embryonal–maternal synchronization. The overall ectopic pregnancy rate after blastocyst transfer was low, comparable with reported ectopic pregnancy rates in spontaneous conceptions. Proper evaluation of tubal and uterine pathologies, optimizing endometrial preparation and the transfer of expanded blastocysts in a frozen embryo transfer cycle, might be beneficial.

Suboptimal endometrial-embryonal synchronization is a risk factor for ectopic pregnancy in assisted reproduction techniques.

Gender incidence of intracytoplasmic morphologically selected sperm injection-derived embryos: a prospective randomized study

Abstract Reproductive immunology has grown in importance in recent years and has even developed into a discipline of its own within the field of reproductive medicine. Many aspects of reproductive failure such as repeated implantation failure or recurrent miscarriages are, meanwhile, seen as a consequence of aberrant expression of immunological factors. This is reflected by the increasing number of tests for assessing and quantifying different immune cell types as well as by a wide range of immune therapies offered to a clientele consisting of desperate patients requesting additional ‘IVF tools’: first, what is still usually disregarded is the enormous plasticity and fluctuation of most immune cells in the genital tract; second, their still poorly characterized functions in the endometrial cycle: further, their partially unknown role in embryo implantation and in establishing a pregnancy; and third, the fact that one of the fundamental hypotheses of reproductive immunology—of note—the Medawar concept or ‘Medawar's Paradox’ of semi-allogeneic graft embryo, is partially based on an erroneous assumption, i.e. the immunologic rejection and tolerance of an embryo. In the present opinion article, we comment on the diagnostic procedures and therapy approaches for chronic endometritis within the scope of reproductive medicine.

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Diagnosing chronic endometritis: when simplification fails to clarify

Neopterin, D-erythro-trihydroxypropylpterin, is a stable, low-molecular mass molecule which is produced in humans and primates by monocytes/macrophages upon stimulation with interferon-(IFN)-γ. In other species only scarce amounts of neopterin are detected. Measurement of neopterin in body fluids provides a sensitive method to estimate the degree of cellular immune activation. IFN-γ is the only known cytokine to directly stimulate neopterin production although others like tumor necrosis factor-α or Interleukin-12 superinduce the quantity of neopterin secretion (1, 2).

Barbara Wirleitner

Papers

Intracytoplasmic Morphologically Selected Sperm Injection

Suboptimal endometrial-embryonal synchronization is a risk factor for ectopic pregnancy in assisted reproduction techniques.

Gender incidence of intracytoplasmic morphologically selected sperm injection-derived embryos: a prospective randomized study

Diagnosing chronic endometritis: when simplification fails to clarify

Neopterin, an Immunodiagnostic and Oxidative Stress Indicator