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

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 (P 4 ) 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 weighsuckle-weigh assay. Mammary β-casein expression, milk yields, litter growth rates, gland structure, and serum concentrations of 17-β estrogen (E 2 ), P 4 , 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 E 2 , P 4 , 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.

Application of an in Vitro Assay to Identify Chemicals That Increase Estradiol and Progesterone Synthesis and Are Potential Breast Cancer Risk Factors

“…These effects may be due to the 2,4-DNT isomer, which is linked to mammary fibroadenomas (IARC 1996;NIOSH 1985). (Zhu et al 2020). Effects on serum P4 levels were conflicting (Barnhart et al 2004;Niinimäki et al 2009;Zhu et al 2020).…”

“…(Zhu et al 2020). Effects on serum P4 levels were conflicting (Barnhart et al 2004;Niinimäki et al 2009;Zhu et al 2020). Mifepristone is a well-established PR antagonist (Ho et al 2002;Kim et al 2020).…”

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials

“…As breastfeeding intensity decreases gradually, basal PRL levels return to normal gradually. PRL deficiency can cause lactation insufficiency [ 60 ]. Pharmacological galactagogues function primarily by stimulating PRL secretion [ 21 ].…”

Polyscias scutellaria Aqueous Leaves Extract Increases Insulin Levels and Improves Mammary Gland Histology in Lactating Rats

“…(7) Breast milk ejection reflex is affected by several hormones that regulate mammary gland development, including insulin. (20) Insulin is a polypeptide hormone secreted by pancreatic β cells which plays a key role in regulating glucose levels in the blood. ( 21) Insulin has been reported to be found in human colostrum at concentrations of 114-306 mU/L, then decrease to similar concentrations to blood insulin levels in day 5 postpartum of healthy mother.…”