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12 August 2019 Role of lysyl oxidase like 1 in regulation of postpartum connective tissue metabolism in the mouse vagina
Ali Borazjani, Bruna M. Couri, Mei Kuang, Brian M. Balog, Margot S. Damaser
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Abstract

Pelvic organ prolapse (POP) in lysyl oxidase like-1 knockout (Loxl1 KO) mice occurs primarily in parous mice and is rare in nulliparous mice. We determined the effect of Loxl1 deficiency on postpartum regulation of connective tissue metabolism genes and degradative enzyme activity in the vagina at 20 days gestation or 4 h, 48 h, 7 days, 15 days, 25 days, 7 weeks, or 12 weeks postpartum. Nulliparous Loxl1 KO and wildtype (WT) mice aged 11, 18, or 23 weeks were controls. Gene expression and enzyme activity were assessed using real-time quantitative reverse transcription PCR and fluorescein conjugated gelatin zymography, respectively. Parity, but not aging, had a significant influence on gene expression both with time postpartum and between KO and WT mice. Mmp2, Timp1, Timp2, Timp3, Timp4, Col1a1, Col3a1, Acta2, and Bmp1 were differentially expressed between KO and WT mice. Correlational analysis of gene-gene pairs revealed 10 significant differences between parous KO and WT groups, 5 of which were due to lack of co-expression of Bmp1 in KO mice. The overall enzyme activity that could be attributed to MMPs was significantly higher in WT compared to KO mice both 25 days and 12 weeks postpartum, and MMP activity was significantly lower 15 days and 25 days postpartum compared to KO nulliparous controls, but not WT. These findings suggest that Loxl1 deficiency combined with parity has a significant impact on postpartum regulation of connective tissue metabolism, particularly as it relates to co-expression of Bmp1 and altered proteolytic activity.

Summary Sentence

Loxl1 deficiency combined with parity has a significant impact on regulation of connective tissue metabolism in the vagina during puerperium, particularly as it relates to the co-expression of genes with Bmp1.

© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Ali Borazjani, Bruna M. Couri, Mei Kuang, Brian M. Balog, and Margot S. Damaser "Role of lysyl oxidase like 1 in regulation of postpartum connective tissue metabolism in the mouse vagina," Biology of Reproduction 101(5), 916-927, (12 August 2019). https://doi.org/10.1093/biolre/ioz148
Received: 19 August 2019; Accepted: 8 August 2019; Published: 12 August 2019
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KEYWORDS
Extracellular matrix
lysyl oxidase like 1
parity
pelvic organ prolapse
postpartum
vagina
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