Biosynthesis and Degradation of Free D-Amino Acids and Their Physiological Roles in the Periphery and Endocrine Glands.

It was long believed that D-amino acids were either unnatural isomers or laboratory artifacts, and that the important functions of amino acids were exerted only by L-amino acids. However, recent investigations have revealed a variety of D-amino acids in mammals that play important roles in physiological functions, including free D-serine and D-aspartate that are crucial in the central nervous system. The functions of several D-amino acids in the periphery and endocrine glands are also receiving increasing attention. Here, we present an overview of recent advances in elucidating the physiological roles of D-amino acids, especially in the periphery and endocrine glands.

The neuroendocrine and endocrine systems in insect - Historical perspective and overview.

A complex cascade of events leads to the initiation and maintenance of a behavioral act in response to both internally and externally derived stimuli. These events are part of a transition of the animal into a new behavioral state, coordinated by chemicals that bias tissues and organs towards a new functional state of the animal. This form of integration is defined by the neuroendocrine (or neurosecretory) system and the endocrine system that release neurohormones or hormones, respectively. Here we describe the classical neuroendocrine and endocrine systems in insects to provide an historic perspective and overview of how neurohormones and hormones support plasticity in behavioral expression. Additionally, we describe peripheral tissues such as the midgut, epitracheal glands, and ovaries, which, whilst not necessarily being endocrine glands in the pure sense of the term, do produce and release hormones, thereby providing even more flexibility for inter-organ communication and regulation.

Preliminary investigation reveals novel pathological consequences of bluetongue virus-1 infection in the endocrine glands of pregnant Indian sheep.

Bluetongue virus (BTV), a major peril to the sheep industry, infects a wide range of the cells in the infected animals including mononuclear, dendritic and epithelial cells. However, little is known about its tropism for the secretory epithelial cells of endocrine glands and the pathogenesis it induces. The aim of the study was to assess the BTV load, antigen distribution in the tissue of the pituitary, thyroid as well as adrenal glands and associated histopathological consequences. BTV antigens were localized using immunohistochemistry in the thyroid's epithelial cells, zona fasciculata and zona reticularis cells and the anterior pituitary epithelial cells. The real-time PCR portrayed the high viral load in adrenals at 7th days postinoculation (DPI) and in thyroid and pituitary glands at 15th DPI. Serum examination revealed variation in the T-3 and T-4 of infected animals in comparison to the control group. Caspase-3 immunolocalization revealed BTV-1 induces apoptosis in the affected cells of endocrine gland of infected animals. Further, this study signifies the tropism of BTV in the novel sites (endocrine glands) of the host that might be one of the reasons for the poor performance of infected animals.

Transcriptome profiling of microdissected cortex and medulla unravels functional regionalization in the European sea bass Dicentrarchus labrax thymus.

The thymus is a sophisticated primary lymphoid organ in jawed vertebrates, but knowledge on teleost thymus remains scarce. In this study, for the first time in the European sea bass, laser capture microdissection was leveraged to collect two thymic regions based on histological features, namely the cortex and the medulla. The two regions were then processed by RNAseq and in-depth functional transcriptome analyses with the aim of revealing differential gene expression patterns and gene sets enrichments, ultimately unraveling unique microenvironments imperative for the development of functional T cells. The sea bass cortex emerged as a hub of T cell commitment, somatic recombination, chromatin remodeling, cell cycle regulation, and presentation of self antigens from autophagy-, proteasome- or proteases-processed proteins. The cortex therefore accommodated extensive thymocyte proliferation and differentiation up to the checkpoint of positive selection. The medulla instead appeared as the center stage in autoimmune regulation by negative selection and deletion of autoreactive T cells, central tolerance mechanisms and extracellular matrix organization. Region-specific canonical markers of T and non-T lineage cells as well as signals for migration to/from, and trafficking within, the thymus were identified, shedding light on the highly coordinated and exquisitely complex bi-directional interactions among thymocytes and stromal components. Markers ascribable to thymic nurse cells and poorly characterized post-aire mTEC populations were found in the cortex and medulla, respectively. An in-depth data mining also exposed previously un-annotated genomic resources with differential signatures. Overall, our findings contribute to a broader understanding of the relationship between regional organization and function in the European sea bass thymus, and provide essential insights into the molecular mechanisms underlying T-cell mediated adaptive immune responses in teleosts.

Single neuron responses underlying face recognition in the human midfusiform face-selective cortex.

Faces are critical for social interactions and their recognition constitutes one of the most important and challenging functions of the human brain. While neurons responding selectively to faces have been recorded for decades in the monkey brain, face-selective neural activations have been reported with neuroimaging primarily in the human midfusiform gyrus. Yet, the cellular mechanisms producing selective responses to faces in this hominoid neuroanatomical structure remain unknown. Here we report single neuron recordings performed in 5 human subjects (1 male, 4 females) implanted with intracerebral microelectrodes in the face-selective midfusiform gyrus, while they viewed pictures of familiar and unknown faces and places. We observed similar responses to faces and places at the single cell level, but a significantly higher number of neurons responding to faces, thus offering a mechanistic account for the face-selective activations observed in this region. Although individual neurons did not respond preferentially to familiar faces, a population level analysis could consistently determine whether or not the faces (but not the places) were familiar, only about 50 ms after the initial recognition of the stimuli as faces. These results provide insights into the neural mechanisms of face processing in the human brain.

Non-uniform temporal scaling of developmental processes in the mammalian cortex.

The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more advanced in dunnarts. We identify a lack of basal intermediate progenitor cells in dunnarts that likely contributes in part to this timing difference. These findings demonstrate temporal limitations and differential plasticity of cortical developmental processes between similarly sized Therians and provide insight into subtle temporal changes that may have contributed to the early diversification of the mammalian brain.

Prominent in vivo influence of single interneurons in the developing barrel cortex.

Spontaneous synchronous activity is a hallmark of developing brain circuits and promotes their formation. Ex vivo, synchronous activity was shown to be orchestrated by a sparse population of highly connected GABAergic 'hub' neurons. The recent development of all-optical methods to record and manipulate neuronal activity in vivo now offers the unprecedented opportunity to probe the existence and function of hub cells in vivo. Using calcium imaging, connectivity analysis and holographic optical stimulation, we show that single GABAergic, but not glutamatergic, neurons influence population dynamics in the barrel cortex of non-anaesthetized mouse pups. Single GABAergic cells mainly exert an inhibitory influence on both spontaneous and sensory-evoked population bursts. Their network influence scales with their functional connectivity, with highly connected hub neurons displaying the strongest impact. We propose that hub neurons function in tailoring intrinsic cortical dynamics to external sensory inputs.

The role of superficial and deep layers in the generation of high frequency oscillations and interictal epileptiform discharges in the human cortex.

Describing intracortical laminar organization of interictal epileptiform discharges (IED) and high frequency oscillations (HFOs), also known as ripples. Defining the frequency limits of slow and fast ripples. We recorded potential gradients with laminar multielectrode arrays (LME) for current source density (CSD) and multi-unit activity (MUA) analysis of interictal epileptiform discharges IEDs and HFOs in the neocortex and mesial temporal lobe of focal epilepsy patients. IEDs were observed in 20/29, while ripples only in 9/29 patients. Ripples were all detected within the seizure onset zone (SOZ). Compared to hippocampal HFOs, neocortical ripples proved to be longer, lower in frequency and amplitude, and presented non-uniform cycles. A subset of ripples (≈ 50%) co-occurred with IEDs, while IEDs were shown to contain variable high-frequency activity, even below HFO detection threshold. The limit between slow and fast ripples was defined at 150 Hz, while IEDs' high frequency components form clusters separated at 185 Hz. CSD analysis of IEDs and ripples revealed an alternating sink-source pair in the supragranular cortical layers, although fast ripple CSD appeared lower and engaged a wider cortical domain than slow ripples MUA analysis suggested a possible role of infragranularly located neural populations in ripple and IED generation. Laminar distribution of peak frequencies derived from HFOs and IEDs, respectively, showed that supragranular layers were dominated by slower (< 150 Hz) components. Our findings suggest that cortical slow ripples are generated primarily in upper layers while fast ripples and associated MUA in deeper layers. The dissociation of macro- and microdomains suggests that microelectrode recordings may be more selective for SOZ-linked ripples. We found a complex interplay between neural activity in the neocortical laminae during ripple and IED formation. We observed a potential leading role of cortical neurons in deeper layers, suggesting a refined utilization of LMEs in SOZ localization.

The Timing Sequence and Mechanism of Aging in Endocrine Organs.

The world is increasingly aging, and there is an urgent need to find a safe and effective way to delay the aging of the body. It is well known that the endocrine glands are one of the most important organs in the context of aging. Failure of the endocrine glands lead to an abnormal hormonal environment, which in turn leads to many age-related diseases. The aging of endocrine glands is closely linked to oxidative stress, cellular autophagy, genetic damage, and hormone secretion. The first endocrine organ to undergo aging is the pineal gland, at around 6 years old. This is followed in order by the hypothalamus, pituitary gland, adrenal glands, gonads, pancreatic islets, and thyroid gland. This paper summarises the endocrine gland aging-related genes and pathways by bioinformatics analysis. In addition, it systematically summarises the changes in the structure and function of aging endocrine glands as well as the mechanisms of aging. This study will advance research in the field of aging and help in the intervention of age-related diseases.

SARS-CoV-2 infection and its effects on the endocrine system.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs, such as the pancreas, adrenal, thyroid, and adipose tissue. The main receptor for SARS-CoV-2, ACE2, is ubiquitously expressed in the cells of the endocrine organs and accordingly, the virus has been detected in various amounts in all endocrine tissues in post-mortem samples from COVID-19 patients. The infection with SARS-CoV-2 may directly lead to organ damage or dysfunction, such as hyperglycaemia or in rare cases, new-onset diabetes. Furthermore, an infection with SARS-CoV-2 may have indirect effects affecting the endocrine system. The exact mechanisms are not yet completely understood and have to be further investigated. Conversely, endocrine diseases may affect the severity of COVID-19 and emphasis has to be laid on reducing the prevalence, or enhance the treatment, of these often non-communicable diseases in the future.

The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma.

The 5th edition of the World Health Organization (WHO) classification of endocrine tumors was released in 2022. Several novelties have been introduced concerning the nomenclature and histopathological diagnosis of follicular-derived thyroid neoplasms. Tumor types have been sharply classified according to prognostic risk categories into benign tumors, low-risk neoplasms and malignant neoplasms. A grading system for differentiated thyroid carcinomas has been implemented with the aim of improving the stratification of tumors. Particular attention has been paid to the molecular profile of well-differentiated histotypes. In this review, the main changes introduced by the latest edition of the WHO system are presented. The practical effects on the diagnostic pathology of thyroid tumors, along with the clinical implications expected with the new classification scheme, are critically discussed.

Progress in salivary glands: Endocrine glands with immune functions.

The production and secretion of saliva is an essential function of the salivary glands. Saliva is a complicated liquid with different functions, including moistening, digestion, mineralization, lubrication, and mucosal protection. This review focuses on the mechanism and neural regulation of salivary secretion, and saliva is secreted in response to various stimuli, including odor, taste, vision, and mastication. The chemical and physical properties of saliva change dynamically during physiological and pathophysiological processes. Moreover, the central nervous system modulates salivary secretion and function via various neurotransmitters and neuroreceptors. Smell, vision, and taste have been investigated for the connection between salivation and brain function. The immune and endocrine functions of the salivary glands have been explored recently. Salivary glands play an essential role in innate and adaptive immunity and protection. Various immune cells such as B cells, T cells, macrophages, and dendritic cells, as well as immunoglobins like IgA and IgG have been found in salivary glands. Evidence supports the synthesis of corticosterone, testosterone, and melatonin in salivary glands. Saliva contains many potential biomarkers derived from epithelial cells, gingival crevicular fluid, and serum. High level of matrix metalloproteinases and cytokines are potential markers for oral carcinoma, infectious disease in the oral cavity, and systemic disease. Further research is required to monitor and predict potential salivary biomarkers for health and disease in clinical practice and precision medicine.

Distribución mutación BRAFsegún carac-terísticas epidemiológicas e histopatológicas en cáncer papilar de tiroides. Un estudio observacional de centro único / BRAFmutation distribution according to epidemiological and histopathological characteristics in papillary thyroid cancer patients. A single-center observational study

Introducción: El cáncer de tiroides se posiciona como una de las neoplasias más prevalentes en Ecuador, manifestándose típicamente en la cuarta década de vida, con una mayor inciden-cia en mujeres. El subtipo histológico predominante es el papilar (CPT), y diversos estudios han evidenciado que hasta un 80% de los casos de CPT presentan la mutación BRAF. Esta mutación se ha asociado con factores de pronóstico desfavorable, como la presencia de me-tástasis ganglionares, estadíos tumorales avanzados, extensión extratiroidea y característi-cas histológicas agresivas. Además, se ha observado una relación con una mayor tasa de recurrencia y una respuesta reducida al tratamiento con yodo. Ante este contexto, esta inves-tigación se propone analizar la distribución de la mutación BRAF según características epide-miológicas e histopatológicas en pacientes con diagnóstico de cáncer papilar de tiroides en Ecuador. Materiales y métodos: Este estudio se llevó a cabo de manera descriptiva y retrospectiva, abarcando a pacientes con diagnóstico de cáncer papilar de tiroides a quienes se les practicó el análisis genético para la detección de la mutación BRAF. La muestra incluyó 106 historias clínicas que cumplían con los criterios de selección establecidos Resultados: La evaluación de las historias clínicas reveló la presencia de la mutación BRAF en el 75% de los casos. Este porcentaje fue más elevado en mujeres, individuos mayores de 45 años y residentes en áreas urbanas. Respecto a la ocupación, la mayoría de los pacientes se dedicaba a labores de limpieza y no presentaban antecedentes personales de exposición a radiación ionizante ni antecedentes oncológicos familiares. El 84% se encontraba en la etapa clínica I, y en su mayoría, la neoplasia estaba localizada en el lóbulo tiroideo derecho.Conclusión:Este análisis subraya la imperiosa necesidad de identificar los factores de riesgo vinculados con la aparición del carcinoma papilar de tiroides en la población ecuatoriana. Los resultados indican una prevalencia significativa de la mutación BRAF, lo que subraya su rele-vancia comomarcador pronóstico en esta enfermedad. Estos hallazgos pueden contribuir a una mejor comprensión de la epidemiología y la patogenia del cáncer de tiroides, así como a la mejora de las estrategias de prevención y tratamiento en el ámbito local.

Introduction: Thyroid cancer is positioned as one of the most prevalent neoplasms in Ecuador, typically manifesting in the fourth decade of life, with a higher incidence in women. The pre-dominant histological subtype is papillary carcinoma (PTC), and various studies presentshown that up to 80% of PTC cases present the BRAF mutation. This mutation has been as-sociated with unfavorable prognostic factors, such as the presence of lymph node metasta-ses, advanced tumor stages, extrathyroidal extension, and aggressive histologicalfeatures. Additionally, a correlationhas been observed with a higher recurrence rate and a reduced re-sponse toiodine treatment. Given this context, this research aims to analyze the distribution of the BRAF mutation according to epidemiological and histopathological characteristics in patients diagnosed with papillary thyroid cancer in Ecuador. Materials and methods: This retrospective descriptive study involved the analysis of genetic data from 106 medical records of patients diagnosed with papillary thyroid cancer who under-went BRAF mutation detection. The sample was selected based on established criteria. Results: Evaluation of medical records revealed the presence of the BRAF mutation in 75% of cases. This percentage was higher in women, individuals over 45 years of age, and residents in urban areas. Regarding occupation, most patients were dedicated to cleaning work and had no personal history of exposure to ionizing radiation orafamily history of cancer.Additionally, 84% of the patients were in clinical stage I and the neoplasmswerelocated in the right thyroid lobe.Conclusion: This analysis highlights the urgent need to identify risk factors linked to the ap-pearance of papillary thyroid carcinoma in the Ecuadorian population. The results indicate a significant prevalence of the BRAF mutation, underlining its relevance as a prognostic marker in this disease. These findings may contribute to a better understanding of the epidemiology and pathogenesis of thyroid cancerleadingtoimprovementsinprevention and treatment strategies at the local level.

Whole-body analysis of TRPML3 (MCOLN3) expression using a GFP-reporter mouse model reveals widespread expression in secretory cells and endocrine glands.

TRPML3 (mucolipin 3, MCOLN3) is an endolysosomal cation channel belonging to the TRPML subfamily of transient receptor potential channels. Gain-of-function mutations in the Trpml3 gene cause deafness, circling behavior and coat color dilution in mice due to cell death of TRPML3-expressing hair cells of the inner ear or skin melanocytes, respectively. Furthermore, TRPML3 was found to play a role in the long term survival of cochlear hair cells (its absence contributing to presbycusis), in specialized giant lysosomes that neonatal (birth to weaning) enterocytes used for the uptake and digestion of maternal milk nutrients, and in the expulsion of exosome-encased bacteria such as uropathogenic E. coli, infecting bladder epithelial cells. Recently, TRPML3 was found to be expressed at high levels in alveolar macrophages and loss of TRPML3 results in a lung emphysema phenotype, confirmed in two independently engineered Trpml3 knockout lines. TRPML3 is not ubiquitously expressed like its relative TRPML1 and thus cellular expression of TRPML3 on a whole-tissue level remains, with the exceptions mentioned above, largely elusive. To overcome this problem, we generated a τGFP reporter mouse model for TRPML3 and compared expression data obtained from this model by immunofluorescence on tissue sections with immunohistochemistry using TRPML3 antibodies and in situ hybridization. We thus uncovered expression in several organs and distinct cell types. We confirmed TRPML3 expression in both neonatal and adult alveolar macrophages, in melanocytes of hair follicles and glabrous skin, in principle cells of the collecting duct of the neonatal and adult kidney, and in olfactory sensory neurons of the olfactory epithelium, including its fibres protruding to the glomeruli of the olfactory bulb. Additionally, we localized TRPML3 in several glands including parathyroid, thyroid, salivary, adrenal, and pituitary gland, testes and ovaries, suggestive of potential roles for the channel in secretion or uptake of different hormones.

Histological and electrophysiological evidence on the safe operation of a sharp-tip multimodal optrode during infrared neuromodulation of the rat cortex.

Infrared neuromodulation is an emerging technology in neuroscience that exploits the inherent thermal sensitivity of neurons to excite or inhibit cellular activity. Since there is limited information on the physiological response of intracortical cell population in vivo including evidence on cell damage, we aimed to create and to validate the safe operation of a microscale sharp-tip implantable optrode that can be used to suppress the activity of neuronal population with low optical power continuous wave irradiation. Effective thermal cross-section and electric properties of the multimodal microdevice was characterized in bench-top tests. The evoked multi-unit activity was monitored in the rat somatosensory cortex, and using NeuN immunocytochemistry method, quantitative analysis of neuronal density changes due to the stimulation trials was evaluated. The sharp tip implant was effectively used to suppress the firing rate of neuronal populations. Histological staining showed that neither the probe insertion nor the heating protocols alone lead to significant changes in cell density in the close vicinity of the implant with respect to the intact control region. Our study shows that intracortical stimulation with continuous-wave infrared light at 1550 nm using a sharp tip implantable optical microdevice is a safe approach to modulate the firing rate of neurons.

[Characterization of Endocrine Glands Involved in Erdheim-Chester Disease].

Objective To investigate the clinical and imaging characteristics of endocrine glands involved in Erdheim-Chester disease (ECD).Methods A retrospective analysis was performed on 48 ECD cases pathologically diagnosed from January 2014 to October 2020 in Peking Union Medical College Hospital,including 22 cases of endocrine gland involvement.The clinical,imaging,and pathological characteristics were summarized. Results Pituitary was involved in 17 cases (17/48,35.4%),adrenal gland in 8 cases (8/48,16.7%),and both pituitary and adrenal gland in 3 cases (3/48,6.25%).The most common symptom in patients with pituitary involvement was central diabetes insipidus (13/17,76.5%),and the T1-weighted imaging showed posterior pituitary hypersignal disappearance,pituitary stalk thickening,and abnormally enhanced pituitary nodules.The most common symptom in patients with adrenal gland involvement was adrenal function reduction (3/8,37.5%),and the CT scanning showed diffuse thickening of adrenal glands.BRAF V600E mutation was positive in 13 (13/22,59.1%) cases with ECD involving endocrine glands.Conclusion Pituitary and adrenal glands are the most common sites of ECD involving endocrine glands.A definite diagnosis can be achieved by combining clinical,imaging,and pathological characteristics for timely treatment.

Endocrine and metabolic complications of COVID-19: lessons learned and future prospects.

Coronavirus disease 2019 (COVID-19) is well known for its respiratory complications; however, it can also cause extrapulmonary manifestations, including cardiovascular, thrombotic, renal, gastrointestinal, neurologic, and endocrinological symptoms. Endocrinological complications of COVID-19 are rare but can considerably impact the outcome of the patients. Moreover, preexisting endocrinologic disorders can affect the severity of COVID-19. Thyroid, pancreas, adrenal, neuroendocrine, gonadal, and parathyroid glands are the main endocrinologic organs that can be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Endocrinological complications of COVID-19 are rare but can significantly deteriorate the patients' prognosis. Understanding the interaction between COVID-19 and the endocrine system can provide a potential treatment option to improve the outcome of COVID-19. In this article, we aim to review the short-term and long-term organ-based endocrinological complications of COVID-19, the pathophysiology, the influence of each complication on COVID-19 prognosis, and potential therapeutic interventions based on current published data. Moreover, current clinical trials of potential endocrinological interventions to develop therapeutic strategies for COVID-19 have been discussed.

Cell Networks in Endocrine/Neuroendocrine Gland Function.

Reproduction, growth, stress, and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a "textbook" view of endocrine gland organization which has emanated from 20th century histological studies on thin 2D tissue sections. However, 21st -century technological advances, including in-depth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multicellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This article focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves. © 2022 American Physiological Society. Compr Physiol 12:3371-3415, 2022.

Loss of imprinting of the Igf2-H19 ICR1 enhances placental endocrine capacity via sex-specific alterations in signalling pathways in the mouse.

Imprinting control region (ICR1) controls the expression of the Igf2 and H19 genes in a parent-of-origin specific manner. Appropriate expression of the Igf2-H19 locus is fundamental for normal fetal development, yet the importance of ICR1 in the placental production of hormones that promote maternal nutrient allocation to the fetus is unknown. To address this, we used a novel mouse model to selectively delete ICR1 in the endocrine junctional zone (Jz) of the mouse placenta (Jz-ΔICR1). The Jz-ΔICR1 mice exhibit increased Igf2 and decreased H19 expression specifically in the Jz. This was accompanied by an expansion of Jz endocrine cell types due to enhanced rates of proliferation and increased expression of pregnancy-specific glycoprotein 23 in the placenta of both fetal sexes. However, changes in the endocrine phenotype of the placenta were related to sexually-dimorphic alterations to the abundance of Igf2 receptors and downstream signalling pathways (Pi3k-Akt and Mapk). There was no effect of Jz-ΔICR1 on the expression of targets of the H19-embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependent changes in signalling.