Testosterone protects mice against zika virus infection and suppresses the inflammatory response in the brain

Zheng, Bohan; Sun, Jian; Luo, Haoran; Yang, Ling’en; Li, Qi; Zhang, Luping; Si, Youhui; Cao, Shengbo; Ye, Jing

doi:10.1016/j.isci.2022.105300

Cited by 4 publications

(2 citation statements)

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“…In this study, however, ZIKV-infected mice did not show a physiological decrease in serum testosterone from birth till adulthood, the pathogenesis of which remains unclear and may be related to the blocked consumption of testosterone. As a protective hormone against ZIKV infection ( 46 ), whether disordered testosterone level in postnatal ZIKV-infected mice affects disease progression needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice

Liu,

Yang,

Chang

et al. 2023

J Virol

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Zika virus (ZIKV) infection in pregnant women during the first trimester can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen. By contrast, ZIKV infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in newborns without microcephaly. Here, we evaluated the long-term fertility consequences of ZIKV infection in male suckling mice, which is equivalent to congenital ZIKV infection in children, from multiple perspectives including the hypothalamic-pituitary-gonadal axis, testis, sperm, and social behaviors. We observed the persistence of ZIKV in the hypothalamus of mice, which caused long-term hormone deficiencies of the hypothalamic-pituitary-gonadal axis. Hormone deficiencies led to limited delays in testicular development, a decrease in sperm quality and quantity, and abnormal social abilities. These damages could progress to diminished fertility in male mice, as judged by lower pregnancy rate, prolonged time to delivery, and decreased offspring quality. Currently, the extent to which these observations in mice translate to humans remains unclear, but longitudinal studies of hormone levels and reproductive health in ZIKV-exposed children seem warranted. IMPORTANCE Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.

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Section: Discussionmentioning

confidence: 99%

Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice

Liu,

Yang,

Chang

et al. 2023

J Virol

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“…In the APP-PS1 transgenic mouse model, the infiltration of cytotoxic CD8 + T-cells into the brain was increased compared with that in age-matched wildtype mice. 48 Additionally, testosterone protected mice from Zika virus infection through reducing CD8 + T-cells infiltration into brains 49 and inhibited the Zika virus infection-induced increases in CCL2 and CCL5 expression in the brain, suggesting that androgen may mediate the peripheral immune cell infiltration in AD pathology through regulation of chemokines.…”

Section: Androgen and Neuroinflammation In Admentioning

confidence: 99%

Role of sex hormones in neuroinflammation in Alzheimer's disease

Maekawa

Yamanaka

2023

Clinical & Exp Neuroim

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Neuroinflammation, which is mediated by microglia, astrocytes, and infiltrated immune cells and leads to the subsequent production of proinflammatory molecules, is associated with the pathomechanism of Alzheimer's disease (AD). As the incidence of AD is higher in females than males, multiple studies have focused on the relationship between sex hormones and AD pathology. Androgen and estrogen receptors are expressed throughout the brain, including the hippocampus; thus, both sex hormones may regulate brain function, including cognitive function. Endogenous sex hormone levels are depleted by aging and cancer therapies, including prostate cancer and breast cancer therapies. Previous cohort studies have revealed that these conditions may also increase the risk of developing AD. Here we review previous findings from epidemiologic and preclinical studies on AD and provide an overview of the roles of sex hormones as risk factors of AD and regulators of AD pathology, including neuroinflammation. Furthermore, we discuss the therapeutic potential of sex hormone supplementation as a preventive or therapeutic treatment for AD based on the results of randomized control trials.

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