Influence of estrous cycle hormonal fluctuations and gonadal hormones on the ventilatory response to hypoxia in female rats

Marques, Danuzia A.; Carvalho, Débora de; Silva, Glauber S. F. da; Szawka, Raphael E.; Anselmo-Franci, Janete Aparecida; Bícego, Kênia C.; Gargaglioni, Luciane H.

doi:10.1007/s00424-017-2022-y

Cited by 26 publications

(19 citation statements)

References 54 publications

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“…While some rodents in our study exhibited relatively high core body temperatures at their LCT in normoxia (e.g. Marques et al 2017;Crew et al 2018; Fig. 1B), their O 2 consumption rates were not elevated, and were comparable to previously reported values (e.g.…”

Section: Series I: Responses To Progressive Cooling In Normoxiasupporting

confidence: 90%

Hypoxia alters the thermogenic response to cold in adult homeothermic and heterothermic rodents

Dzal

Milsom

2019

The Journal of Physiology

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Key points For small mammals living in a cold, hypoxic environment, supplying enough O2 to sustain thermogenesis can be challenging. While heterothermic mammals are generally more tolerant of cold and hypoxia than homeothermic mammals, how they regulate O2 supply and demand during progressive cooling in hypoxia is largely unknown. We show that as ambient temperature is reduced in hypoxia, body temperature falls in both homeotherms and heterotherms. In the homeothermic rat, a decrease in O2 consumption rate and lung O2 extraction accompany this fall in body temperature, despite a relative hyperventilation. Paradoxically, in heterothermic mice, hamsters and ground squirrels, body temperature decreases more than in the homeothermic rat, even though they maintain ventilation, increase lung O2 extraction and maintain or elevate their O2 consumption rates. Variation in cold and hypoxia tolerance among homeotherms and heterotherms reflects divergent strategies in how O2 supply and demand are regulated under thermal and hypoxic challenges. Abstract Compared to homeothermic mammals, heterothermic mammals are reported to be exceptionally tolerant of cold and hypoxia. We hypothesised that this variation in tolerance stems from divergent strategies in how homeotherms and heterotherms regulate O2 supply versus O2 demand when exposed to hypoxia during progressive cooling. To test this hypothesis, we exposed adult rodents ranging in their degree of heterothermic expression (homeotherm: rats, facultative heterotherms: mice and hamsters, and obligate heterotherm: ground squirrels) to either normoxia (21% O2) or environmental hypoxia (7% O2), while reducing ambient temperature from 38 to 5°C. We found that when ambient temperature was reduced in normoxia, all species increased their O2 consumption rate and ventilation in parallel, maintaining a constant ventilatory equivalent and level of lung O2 extraction. Surprisingly, body temperature fell in all species, significantly so in the heterotherms. When ambient temperature was reduced in hypoxia, however, the homeothermic rat decreased their O2 consumption rate and lung O2 extraction despite an increase in their ventilatory equivalent, indicative of a relative hyperventilation. Heterotherms (mice, hamsters and ground squirrels), on the other hand, decreased their ventilatory equivalent, but increased lung O2 extraction and maintained or elevated their O2 consumption rates, yet their body temperature fell even more than in the rat. These results are consistent with the idea that homeotherms and heterotherms diverge in the strategies they use to match O2 supply and O2 demand, and that enhanced cold and hypoxia tolerance in heterotherms may stem from an improved ability to extract O2 from the inspired air.

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Section: Series I: Responses To Progressive Cooling In Normoxiasupporting

confidence: 90%

Hypoxia alters the thermogenic response to cold in adult homeothermic and heterothermic rodents

Dzal

Milsom

2019

The Journal of Physiology

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“…In addition, samples predominantly consisted of keratinized squamous cells and abundant leukocytes were regarded as metaestrus. In terms of diestrus, smears were almost leukocytes in the whole scene [ 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Human Menstrual Blood-Derived Stromal Cells Promote Recovery of Premature Ovarian Insufficiency Via Regulating the ECM-Dependent FAK/AKT Signaling

Feng

Tan

2018

Stem Cell Rev and Rep

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POI is characterized by “absent not abnormal” menstruation with hormonal disorders in woman younger than 40 years of age, and etiological and pathophysiological mechanisms underlying the POI development have not been clearly defined. Recently, due to advantages such as abundant sources and non-invasive methods of harvest, MenSCs have been emerging as a promising treatment strategy for the recovery of female reproductive damage. Here, we demonstrated that MenSCs graft in POI mice after CTX treatment could restore ovarian function by regulating normal follicle development and estrous cycle, reducing apoptosis in ovaries to maintain homeostasis of microenvironment and modulating serum sex hormones to a relatively normal status. Moreover, MenSCs participated in the activation of ovarian transcriptional expression in ECM-dependent FAK/AKT signaling pathway and thus restored ovarian function to a certain extent. MenSCs transplantation was proved to be an effective way to repair ovarian function with low immunogenicity, suggesting its great potential for POI treatment. Electronic supplementary material The online version of this article (10.1007/s12015-018-9867-0) contains supplementary material, which is available to authorized users.

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“…It is possible that all sex hormones have a direct effect on EPO and hepcidin levels and iron metabolism, which directly contribute to the increased hematocrit under hypoxia [48][49][50][51][52][53][54][55][56][57] . Physiological factors, such as ventilation, cardiopulmonary responses, and oxygenation, also depend on sex hormones and can also produce differences in hematocrit levels between the two sexes 25,[58][59][60][61][62][63][64][65] . Our in vitro model system provides a unique opportunity to study the effect of sex hormones at the cellular level in erythroid cells.…”

Section: Discussionmentioning

confidence: 99%

Protective role of estrogen against excessive erythrocytosis in Monge’s disease

et al. 2021

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Monge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features of CMS is excessive erythrocytosis with extremely high hematocrit levels. In the Andean population, CMS prevalence is vastly different between males and females, being rare in females. Furthermore, there is a sharp increase in CMS incidence in females after menopause. In this study, we assessed the role of sex hormones (testosterone, progesterone, and estrogen) in CMS and non-CMS cells using a well-characterized in vitro erythroid platform. While we found that there was a mild (nonsignificant) increase in RBC production with testosterone, we observed that estrogen, in physiologic concentrations, reduced sharply CD235a+ cells (glycophorin A; a marker of RBC), from 56% in the untreated CMS cells to 10% in the treated CMS cells, in a stage-specific and dose-responsive manner. At the molecular level, we determined that estrogen has a direct effect on GATA1, remarkably decreasing the messenger RNA (mRNA) and protein levels of GATA1 (p < 0.01) and its target genes (Alas2, BclxL, and Epor, p < 0.001). These changes result in a significant increase in apoptosis of erythroid cells. We also demonstrate that estrogen regulates erythropoiesis in CMS patients through estrogen beta signaling and that its inhibition can diminish the effects of estrogen by significantly increasing HIF1, VEGF, and GATA1 mRNA levels. Taken altogether, our results indicate that estrogen has a major impact on the regulation of erythropoiesis, particularly under chronic hypoxic conditions, and has the potential to treat blood diseases, such as high altitude severe erythrocytosis.

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Influence of estrous cycle hormonal fluctuations and gonadal hormones on the ventilatory response to hypoxia in female rats

Cited by 26 publications

References 54 publications

Hypoxia alters the thermogenic response to cold in adult homeothermic and heterothermic rodents

Hypoxia alters the thermogenic response to cold in adult homeothermic and heterothermic rodents

Human Menstrual Blood-Derived Stromal Cells Promote Recovery of Premature Ovarian Insufficiency Via Regulating the ECM-Dependent FAK/AKT Signaling

Protective role of estrogen against excessive erythrocytosis in Monge’s disease

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