Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice.
Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice.
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DOI：
10.1128/jvi.01006-23
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发表时间：
2023-10-31
影响因子：
5.4
通讯作者：
An, Jing
中科院分区：
文献类型：
--
作者：
Liu, Li-Bo;Yang, Wei;Chang, Jia-Tong;Fan, Dong-Ying;Wu, Yan-Hua;Wang, Pei-Gang;An, Jing
寨卡病毒（ZIKV）感染孕妇在怀孕的前三个月可能会导致先天性畸形，包括小头畸形，这引起了全球对这种新兴病原体的关注。相比之下，妊娠晚期孕妇的ZIKV感染可导致无小头畸形的新生儿的神经发育延迟和隐睾症。在这里，我们从多个角度评估了雄性乳鼠中ZIKV感染的长期生育后果，这相当于儿童中的先天性ZIKV感染，包括下丘脑-垂体-性腺轴，睾丸，精子和社会行为。我们观察到ZIKV在小鼠下丘脑中的持续存在，这导致下丘脑-垂体-性腺轴的长期激素缺乏。激素缺乏导致睾丸发育有限延迟，精子质量和数量下降，以及社会能力异常。这些损害可能会导致雄性小鼠生育能力下降，如妊娠率降低、分娩时间延长和后代质量下降。目前，这些在小鼠身上的观察结果在多大程度上转化为人类尚不清楚，但对接触ZIKV的儿童的激素水平和生殖健康进行纵向研究似乎是有必要的。孕妇在妊娠晚期感染寨卡病毒（ZIKV）可导致无小头畸形的儿童神经发育迟缓和隐睾症。然而，先天性ZIKV感染对这些儿童生育能力的影响仍不清楚。在这里，使用免疫活性小鼠模型，我们揭示了先天性ZIKV感染可引起下丘脑-垂体-性腺轴的激素紊乱，导致生育力降低和性偏好降低。我们的研究首次将下丘脑与ZIKV感染后的生殖系统和社会行为联系起来。尽管这些在小鼠中的观察结果在多大程度上转化为人类尚不清楚，但这些发现确实表明，暴露于ZIKV的儿童的生殖健康和激素水平应该得到更多关注，以改善他们的生活质量。
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. 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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影响因子：
30.3
作者：
Miner JJ;Diamond MS
通讯作者：
Diamond MS
影响因子：
2
作者：
de Vasconcelos RAL;Ximenes RAA;Calado AA;Martelli CMT;Gonçalves AV;Brickley EB;de Araújo TVB;Rocha MAW;Miranda-Filho DB
通讯作者：
Miranda-Filho DB
影响因子：
17.1
作者：
Mavigner M;Raper J;Kovacs-Balint Z;Gumber S;O'Neal JT;Bhaumik SK;Zhang X;Habib J;Mattingly C;McDonald CE;Avanzato V;Burke MW;Magnani DM;Bailey VK;Watkins DI;Vanderford TH;Fair D;Earl E;Feczko E;Styner M;Jean SM;Cohen JK;Silvestri G;Johnson RP;O'Connor DH;Wrammert J;Suthar MS;Sanchez MM;Alvarado MC;Chahroudi A
通讯作者：
Chahroudi A
影响因子：
7.1
作者：
Cumberworth SL;Barrie JA;Cunningham ME;de Figueiredo DPG;Schultz V;Wilder-Smith AJ;Brennan B;Pena LJ;Freitas de Oliveira França R;Linington C;Barnett SC;Willison HJ;Kohl A;Edgar JM
通讯作者：
Edgar JM
影响因子：
3.3
作者：
de Vasconcelos, Romulo A. L.;Ximenes, Ricardo A. A.;Miranda-Filho, Democrito de B.
通讯作者：
Miranda-Filho, Democrito de B.