Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia.

Hongmei Zhu,Yi Ding,Mingli Ren,Jianguo Chen,Xuchen Jia,Mingxing Ding,Liguo Yang,Li Han

doi:10.3389/fcell.2020.00102

Hongmei Zhu, Yi Ding + Show 6 more

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https://doi.org/10.3389/fcell.2020.00102

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Abstract

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.

Highlights

Breast milk is the first and the ideal nutritional option for infants (Czosnykowska-Lukacka et al, 2018)
In the pregnancy day 4 (Pd4) + Pd8 strategy, milk yields from the mifepristone group were less than those from the control group on lactation day 1 (Ld1) and Ld2 (P = 0.001 and P = 0.013, respectively), but no different in milk yield was found between two groups on lactation day 3 (Ld3) (Figure 2B)
In the Pd8 strategy, mifepristone-treated mice showed no change in milk yields on Ld1 and Ld2, but exhibited a significant reduction on Ld3 (P = 0.04) compared to those from the control group (Figure 2C)

Summary

Introduction

Breast milk is the first and the ideal nutritional option for infants (Czosnykowska-Lukacka et al, 2018). The syndrome accompanied with a primary clinical sign of the sow’s inability to produce sufficient milk to meet the nutritional requirements of piglets was named as postpartum dysgalactia syndrome (PDS) or postpartum hypogalactia syndrome (PHS). These syndromes in sows are observed almost within the first 3 days postpartum and can cause decreased growth performance, depression, or diarrhea in piglets (Marchant et al, 2000; Bilkei, 2005; Klopfenstein et al, 2006; Preissler et al, 2012). All the factors above are likely to disturb the entire endocrine system, which may adversely affect the mammary gland development and lactation

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