Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model.
Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model.
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DOI：
10.1016/j.ebiom.2023.104762
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发表时间：
2023-09
期刊：
影响因子：
11.1
通讯作者：
Serghides, Lena
中科院分区：
文献类型：
--
作者：
Mohan, Haneesha;Nguyen, Jessica;Mackenzie, Ben;Yee, Audrey;Laurette, Evelyn Yukino;Sanghvi, Tanvi;Tejada, Oscar;Dontsova, Valeriya;Leung, Kit-Yi;Goddard, Cameron;De Young, Taylor;Sled, John G.;Greene, Nicholas D. E.;Copp, Andrew J.;Serghides, Lena
Dolutegravir （DTG）是所有人类免疫缺陷病毒（HIV）感染患者推荐的一线治疗方案。博茨瓦纳是一个没有叶酸强化计划的国家，最初的研究结果显示，在孕产期接触DTG会增加神经管缺陷（NTDs）的患病率。在这里，我们探讨低叶酸饮食是否会影响小鼠模型中dtg相关胎儿异常的风险。C57BL/6小鼠饲喂叶酸缺乏饮食2周，交配后随机分为对照组（水）、1xDTG （2.5 mg/kg）、5xDTG (12.5 mg/kg)，均口服50 mg/kg富马酸替诺福韦二氧吡酯33.3 mg/kg恩曲他滨。治疗从妊娠日（GD） 0.5至牺牲日（GD15.5）每天1次。评估胎儿是否有明显异常。测定母体和胎儿叶酸水平。共313株，其中对照组103株，1xDTG 106株，5xDTG 104株。各组间生存力、胎盘重量和胎儿重量均无差异。仅在DTG组中观察到NTDs（凋落率：0%对照；1.0% 1xDTG; 1.3% 5xDTG）。与对照组相比，DTG组的尾部、腹壁、肢体、颅面和出血缺陷发生率均较高。与我们之前在叶酸充足的怀孕小鼠中使用双甘油三酯的研究结果相比，叶酸缺乏与几种缺陷（包括NTDs）的较高发生率相关，但仅在双甘油三酯组中存在。我们观察到严重的左右不对称表型在DTG组中比对照组更常见。母体叶酸缺乏可能增加dtg相关胎儿缺陷的风险。对于在怀孕期间服用DTG的艾滋病毒感染妇女，特别是在缺乏叶酸强化计划的国家，可以考虑围孕期补充叶酸。该项目由联邦基金资助，根据合同编号。HHSN275201800001I和奖励#R01HD104553。LS由一级和艾滋病毒支持。HM得到了来自。
Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. This project has been funded by Federal funds from the , , under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 and HIV. HM is supported by a Junior Investigator award from the .
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影响因子：
11.1
作者：
Gilmore JC;Hoque MT;Dai W;Mohan H;Dunk C;Serghides L;Bendayan R
通讯作者：
Bendayan R
影响因子：
8.8
作者：
Leung KY;Pai YJ;Chen Q;Santos C;Calvani E;Sudiwala S;Savery D;Ralser M;Gross SS;Copp AJ;Greene NDE
通讯作者：
Greene NDE
影响因子：
3.8
作者：
Cabrera, Robert M.;Souder, Jaclyn P.;Finnell, Richard H.
通讯作者：
Finnell, Richard H.
影响因子：
2.4
作者：
Mahajan, Niraj N.;Mahajan, Kshitija N.;Gaikwad, Nilima L.
通讯作者：
Gaikwad, Nilima L.
影响因子：
5.6
作者：
Finnell, RH;Gould, A;Spiegelstein, O
通讯作者：
Spiegelstein, O