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Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury.

ABSTRACT: In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies.

SUBMITTER: Stewart AN

PROVIDER: S-EPMC7419700 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAfter spinal cord injury (SCI), individuals are typically considered by the general public to be asexual. Handicapped women have more problems with socio-sexual adaptation, stemming from low self-confidence, low self-esteem, and the absence of spontaneity.AimsTo determine changes in the sexual lives of women after SCI.MethodsA self-constructed questionnaire was used to map sexual function after SCI. We retrospectively compared sexual function in 30 women with SCI with that in 30 without SCI who led an active sexual life. Descriptive and inductive statistics were applied using the Student paired and non-paired t-tests and the Levene test.Main outcome measuresThe main variables were presence vs absence of sexual dysfunction in a group of women after SCI and a comparison of the incidence of sexual dysfunctions in women after SCI with that of a control group.ResultsA significant difference was ascertained in women with SCI in sexual desire (P < .001), lubrication (P < .001), and reaching orgasm before and after injury (P = .030). A comparison of the two groups showed a significant difference in the realization of coital sexual activity (P < .001), erotogenous zones of the mouth (P = .016), nipples (P = .022), and genitals (P < .001), and in the ability to reach orgasm (P = .033). The negative impact of incontinence on the sexual life of women with SCI proved significant (P < .001). Negative factors for sexual activity in women with SCI were lower sensitivity in 16 (53%), spasms and mobility problems in 12 (40%), lower desire in 11 (36%), pain in 4 (13%), and a less accommodating partner in 3 (10%).ConclusionIntercourse was the preferred sexual activity in women with SCI. Compared with the period before injury, there was significant lowering of sexual desire, impaired lubrication, and orgasmic ability after SCI. A comparison of the two groups showed a difference in erotogenous zones and in reaching orgasm. Sramkova T, Skrivanova K, Dolan I, et al. Women's Sex Life After Spinal Cord Injury. Sex Med 2017;5:e255-e259.

Project description:Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. Modulation of biological pathways can drive the developing lung towards proper repair or persistent maldevelopment after injury that can lead to a disease phenotype. Sex as a biological variable can modulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung at single-cell resolution and delineate the alterations in the immune-endothelial cell communication networks in the developing lung using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic lung injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1) andpostnatal day 21 (PND 21) neonatal male and female C57BL/6 mice exposed to 95% FiO2between PND 1-5 (saccular stage of lung development).We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the cross-talk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and therapeutic interventions while highlighting the crucial role of sex as a biological variable.

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Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury.

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