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14 August 2017 Seipin deficiency leads to defective parturition in mice
Ahmed E. El Zowalaty, Xiaoqin Ye
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Abstract

Seipin is an integral endoplasmic reticulum membrane protein encoded by Berardinelli–Seip congenital lipodystrophy type 2 (BSCL2/Bscl2) gene. Seipin deficiency results in lipodystrophy, diabetes, muscle hypertrophy, andmale infertility in both human andmouse. Seipin function in female reproduction is unknown. Bscl2-/- dams had normal embryo implantation and body weight gain during pregnancy but reduced delivery rates from 2nd to 4th pregnancies and reduced numbers of pups delivered from 1st to 4th pregnancies. Characterization of first pregnancy revealed increased gestation period and parturition problems, including uterine prolapse, difficulty in delivery, undelivered fetuses, and undelivered tissues in Bscl2-/- females. Bscl2-/- uterine weight was comparable to control at 3 weeks old but significantly increased with myometrial hypertrophy at 10 months old. In situ hybridization revealed relatively low level of Bscl2 mRNA expression in myometrium throughout pregnancy and postpartum but high level of expression in uterine luminal epithelium, suggesting that systemic effect (e.g. elevated glucose and insulin levels) rather than local seipindeficiency in myometrium might be a main contributing factor to myometrial hypertrophy. On near-term gestation day 18.5 (D18.5), Bscl2-/- females had normal levels of serum progesterone and 17β-estradiol, indicating functional ovary and placenta. Proliferating Cell Nuclear Antigen (PCNA) staining showed minimal myometrial cell proliferation in both D18.5 Bscl2+/+ and Bscl2-/- uteri. There was strong LC3 immunostaining in Bscl2+/+ and Bscl2-/- peripartum myometrium and increased LC3 staining in Bscl2-/- peripartum uterine luminal epithelium, suggesting a potential role of seipin in regulating autophagy in uterine luminal epithelium but not myometrium. This study demonstrates an association of seipin with myometrium and parturition.

Summary Sentence

Our findings that seipin deficiency in mice leads to myometrial hypertrophy and parturition problems reveal a novel in vivo function of seipin in parturition.

© The Authors 2017. 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
Ahmed E. El Zowalaty and Xiaoqin Ye "Seipin deficiency leads to defective parturition in mice," Biology of Reproduction 97(3), 378-386, (14 August 2017). https://doi.org/10.1093/biolre/iox088
Received: 4 April 2017; Accepted: 10 August 2017; Published: 14 August 2017
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