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      Physiological effects of high‐altitude trekking on gonadal, thyroid hormones and macrophage migration inhibitory factor (MIF) responses in young lowlander women


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          Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor ( MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high‐altitude hypoxic environment, particularly MIF.

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          MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia.

          Cytokines are critical in the often fatal cascade of events that cause septic shock. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli, and initiates the increase in systemic glucocorticoids that accompanies host stress responses. To assess further the contribution of the pituitary to systemic inflammatory processes, we examined the secretory profile of cultured pituitary cells and whole pituitaries in vivo after stimulation with bacterial lipopolysaccharide (LPS). Here we identify macrophage migration inhibitory factor (MIF) as a major secreted protein release by anterior pituitary cells in response to LPS stimulation. Serum analysis of control, hypophysectomized and T-cell-deficient (nude) mice suggests that pituitary-derived MIF contributes to circulating MIF present in the post-acute phase of endotoxaemia. Recombinant murine MIF greatly enhances lethality when co-injected with LPS and anti-MIF antibody confers full protection against lethal endotoxaemia. We conclude that MIF plays a central role in the toxic response to endotoxaemia and possibly septic shock.
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            The effect of high altitude and other risk factors on birthweight: independent or interactive effects?

            This study examined whether the decline in birth-weight with increasing altitude is due to an independent effect of altitude or an exacerbation of other risk factors. Maternal, paternal, and infant characteristics were obtained from 3836 Colorado birth certificates from 1989 through 1991. Average altitude of residence for each county was determined. None of the characteristics related to birthweight (gestational age, maternal weight gain, parity, smoking, prenatal care visits, hypertension, previous small-for-gestational-age infant, female newborn) interacted with the effect of altitude. Birthweight declined an average of 102 g per 3300 ft (1000 m) elevation when the other characteristics were taken into account, increasing the percentage of low birthweight by 54% from the lowest to the highest elevations in Colorado. High altitude acts independently from other factors to reduce birthweight and accounts for Colorado's high rate of low birthweight.
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              Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m.

              Here we test the hypothesis that high-altitude native resident Tibetan women with genotypes for high oxygen saturation of hemoglobin, and thus less physiological hypoxic stress, have higher Darwinian fitness than women with low oxygen saturation genotypes. Oxygen saturation and genealogical data were collected from residents of 905 households in 14 villages at altitudes of 3,800-4,200 m in the Tibet Autonomous Region along with fertility histories from 1,749 women. Segregation analysis confirmed a major gene locus with an autosomal dominant mode of inheritance for high oxygen saturation levels, associated with a 10% higher mean. Oxygen saturation genotypic probability estimators were then used to calculate the effect of the inferred oxygen saturation locus on measures of fertility, in a subsample of 691 women (20-59 years of age and still married to their first husbands, those with the highest exposure to the risk of pregnancy). The genotypic probability estimators were not significantly associated with the number of pregnancies or live births. The high oxygen saturation genotypic mean offspring mortality was significantly lower, at 0.48 deaths compared with 2.53 for the low oxygen saturation homozygote, because of lower infant mortality. Tibetan women with a high likelihood of possessing one to two alleles for high oxygen saturation had more surviving children. These findings suggest that high-altitude hypoxia is acting as an agent of natural selection on the locus for oxygen saturation of hemoglobin by the mechanism of higher infant survival of Tibetan women with high oxygen saturation genotypes.

                Author and article information

                Physiol Rep
                Physiol Rep
                Physiological Reports
                John Wiley and Sons Inc. (Hoboken )
                25 October 2017
                November 2017
                : 5
                : 20 ( doiID: 10.1002/phy2.2017.5.issue-20 )
                : e13400
                [ 1 ] Department of Neuroscience, Imaging and Clinical Sciences “G. d'Annunzio” University of Chieti‐Pescara Chieti Italy
                [ 2 ] Department of Life Sciences University of Siena Siena Italy
                [ 3 ] Department of Medicine, Surgery and Neuroscience University of Siena Siena Italy
                [ 4 ] Libera Università di Alcatraz Umbria Italy
                Author notes
                [*] [* ] Correspondence

                Vittore Verratti, Department of Neurosciences, Imaging and Clinical Sciences, Laboratory of Functional Evaluation, “G. d'Annunzio” University, Chieti‐Pescara, Italy.

                Tel: +393395359831

                E‐mail: vittorelibero@ 123456hotmail.it

                Author information
                © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                : 26 May 2017
                : 06 July 2017
                : 02 August 2017
                Page count
                Figures: 3, Tables: 2, Pages: 9, Words: 5373
                Funded by: universities of Chieti and Siena
                Reproductive Physiology
                Original Research
                Original Research
                Custom metadata
                November 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:30.10.2017

                hormones,macrophage migration inhibitory factor,women at high altitude


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