Pregnancy in postpartum estrus induces inflammatory milk production and catagen specific pup skin inflammation in interleukin-10 deficient mice.
BACKGROUND
The interleukin 10 deficient mice (IL-10(-/-)) showed high incidence of pup alopecia compared to other strains, and pup alopecia was caused by skin inflammation and was recoverable. Pup alopecia of B6.IL-10(-/-) might be related with maternal factor and interleukin-10 deficient phenotype.


OBJECTIVE
The objectives of this study were elucidating of maternal factors for inflammatory milk production and characterization of pup alopecia in IL-10(-/-) mice.


METHODS
Incidences of pup alopecia were analyzed with 13 breeding cases. Comparison between control and alopecia pups and its dams, were conducted with histological examination (H&E, TUNEL assay, immunohistochemistry for F4/80, iNOS, CD206, Gr-1, CD4, CD8, CD11c and CD326), fostering test, forced weaning test, qPCR for tyrosine hydroxylase, flow cytometry, IL-10 inhibition test, BMDM stimulation test and LC/MS analysis.


RESULTS
Presence of pregnancy in postpartum estrus showed significant correlation with inflammatory milk production and mammary gland involution in B6.IL-10(-/-) mice. There were no different mass in inflammatory milk, but different ionization intensity was detected. Inflammatory milk directly induced hepatocyte steatosis, catagen stage specific hair breaking and alopeicia in pups. Histologically, hypertropy of outer root sheath and macrophage/neutrophil infiltration were typical.


CONCLUSIONS
B6.IL-10(-/-) dam with stress such as PPE could produce untimely mammary gland involution and inflammatory milk production. Interleukin 10 is important for maternal stress regulation and protecting inflammatory milk production, also influence severity of pup skin inflammation and alopecia. Remarkably, inflammatory milk induced hepatocyte steatosis, and it could indicate there is abnormal lipid metabolism. This was first report for catagen specific alopecia in mouse.
Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Woo-Sung
WS
Hwang
Hyun-Il
HI
Kim
You-Jeong
YJ
Kim
Byeong-Cheol
BC
Kang
Hak-Sun
HS
Lee
Keun-Hee
KH
Oh
Dong-Sup
DS
Lee
Su-Cheong
SC
Yeom
D000505:Alopecia / Q000209:etiology*; D000818:Animals; D003872:Dermatitis / Q000209:etiology; D004195:Disease Models, Animal; D004971:Estrus; D005260:Female; D016753:Interleukin-10 / Q000172:deficiency*; D007774:Lactation; D008297:Male; D008321:Mammary Glands, Animal / Q000502:physiology; D051379:Mice; D008892:Milk / Q000009:adverse effects* / Q000737:chemistry; D049590:Postpartum Period; D011247:Pregnancy; D013312:Stress, Physiological
C556062:IL10 protein, mouse; D016753:Interleukin-10
Alopecia; Inflammatory milk; Interleukin-10; Postpartum estrus pregnancy; Stress