Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia
Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia
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米非司酮治疗妊娠小鼠模型诱发的乳腺发育不良和产后缺乳
DOI：
10.3389/fcell.2020.00102
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发表时间：
2020-02
影响因子：
5.5
通讯作者：
Mingxing Ding
中科院分区：
文献类型：
--
作者：
Hongmei Zhu;Xuchen Jia;Mingli Ren;Liguo Yang;Jianguo Chen;Li Han;Yi Ding;Mingxing Ding
乳腺发育不良和产后缺乳经常发生在人类和畜牧业中。然而，它们的潜在机制尚不清楚。米非司酮对孕酮 (P4) 和糖皮质激素受体具有高亲和力，被用来诱导乳腺发育和泌乳失调。设计了四种用米非司酮治疗怀孕小鼠的策略。在第一种策略中，小鼠在妊娠第 4 天 (Pd4) 时按 1.20 毫克米非司酮/公斤体重 (BW) 给药。在第二种策略中，米非司酮对小鼠给药两次，Pd4 时剂量为 1.20 mg/kg BW，Pd8 时剂量为 0.40 mg/kg BW。在第三种策略中，小鼠在 Pd8 上接受单剂量 0.40 mg 米非司酮/kg BW 治疗。在第四种策略中，在第8天给予小鼠0.40毫克米非司酮/千克体重，在第12天给予0.20毫克米非司酮/千克体重。结果表明，根据称重-哺乳-称重测定法的评估，在 Pd4 上按 1.20 mg/kg BW 剂量施用米非司酮会导致哺乳第 1 天 (Ld1)、Ld2 和 Ld3 的产奶量显着减少。在执行第一个 (Pd4) 策略后，在妊娠或哺乳期间测定乳房 β-酪蛋白表达、产奶量、窝生长率、腺体结构和 17-β 雌激素 (E2)、P4、催乳素 (PRL)、生长激素 (GH)、皮质酮 (CORT) 和催产素 (OT) 的血清浓度以及这些激素的受体。结果表明，妊娠早期服用米非司酮可降低β-酪蛋白表达、产奶量和窝产仔生长率，诱导肺泡减少，肺泡腔增大，并改变妊娠或哺乳早期的E2、P4、PRL、GH、CORT和OT水平以及这些激素受体的mRNA表达。目前对接受米非司酮治疗的怀孕小鼠的研究提供了一种创新的小鼠模型来研究乳腺发育不良和产后缺乳的机制。
Mammary gland dysplasia and postpartum hypogalactia often occur in humans and in the livestock breeding industry. However, their underlying mechanisms are not clear yet. Mifepristone, which has a high affinity for progesterone (P4) and glucocorticoid receptors, was exploited here to induce the disorders of mammary gland development and lactation. Four strategies were devised for treating pregnant mice with mifepristone. In the first strategy, mice were administered 1.20 mg mifepristone/kg body weight (BW) on pregnancy day 4 (Pd4). In the second strategy, mifepristone was administered to mice twice, with 1.20 mg/kg BW on Pd4 and 0.40 mg/kg BW on Pd8. In the third strategy, mice were treated with a single dose of 0.40 mg mifepristone/kg BW on Pd8. In the fourth strategy, mice were administered 0.40 mg mifepristone/kg BW on Pd8 and 0.20 mg mifepristone/kg BW on Pd12. The results suggested that mifepristone administration at the dose of 1.20 mg/kg BW on Pd4 caused significant reduction in milk production on lactation day 1 (Ld1), Ld2, and Ld3, as assessed using a weigh-suckle-weigh assay. Mammary β-casein expression, milk yields, litter growth rates, gland structure, and serum concentrations of 17-β estrogen (E2), P4, prolactin (PRL), growth hormone (GH), corticosterone (CORT) and oxytocin (OT) as well as the receptors of these hormones were determined during pregnancy or lactation after performing the first (Pd4) strategy. The results demonstrated that mifepristone administration during early pregnancy decreased β-casein expression, milk yields and litter growth rates, induced fewer alveoli, enlarged alveolar lumina, and altered the levels of E2, P4, PRL, GH, CORT, and OT as well as the mRNA expression of these hormonal receptors during pregnancy or early lactation. The present study on pregnant mice treated with mifepristone offers an innovative murine model to study the mechanism underlying mammary gland dysplasia and postpartum hypogalactia.
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影响因子：
6.7
作者：
L. Kettel;L. Kettel;A. Murphy;A. Murphy;A. Morales;A. Morales;A. Ulmann;A. Ulmann;E. Baulieu;E. Baulieu;S. Yen;S. Yen
通讯作者：
L. Kettel;L. Kettel;A. Murphy;A. Murphy;A. Morales;A. Morales;A. Ulmann;A. Ulmann;E. Baulieu;E. Baulieu;S. Yen;S. Yen
DOI：
10.1016/j.jsbmb.2017.04.011
发表时间：
2018-03
期刊：
The Journal of steroid biochemistry and molecular biology
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作者：
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通讯作者：
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1985
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通讯作者：
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DOI：
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发表时间：
2012-04
期刊：
Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie
影响因子：
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作者：
R. Preissler;D. Hinrichs;K. Reiners;H. Looft;N. Kemper
通讯作者：
R. Preissler;D. Hinrichs;K. Reiners;H. Looft;N. Kemper
DOI：
10.1055/s-2007-1004854
发表时间：
1990-02
期刊：
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
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作者：
J. Llopis;A. Lampreabe;M. López Frías;F. Perán;N. Blanco Martínez;G. Urbano;M. Montellano
通讯作者：
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