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不同光照周期暴露方案下褪黑素给药对小鼠胚胎着床及子代生长的影响

Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure.

作者信息

Zhang Lu, Zhang Zhenzhen, Wang Feng, Tian Xiuzhi, Ji Pengyun, Liu Guoshi

机构信息

State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Present Address: Department of Animal Sciences, Purdue University, West Lafayette, IN, 47907, USA.

出版信息

Reprod Biol Endocrinol. 2017 Oct 2;15(1):78. doi: 10.1186/s12958-017-0297-7.

DOI:10.1186/s12958-017-0297-7
PMID:28969693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5625829/
Abstract

BACKGROUND

Embryo implantation is crucial for animal reproduction. Unsuccessful embryo implantation leads to pregnancy failure, especially in human-assisted conception. Environmental factors have a profound impact on embryo implantation. Because people are being exposed to more light at night, the influence of long-term light exposure on embryo implantation should be explored.

METHODS

The effects of long photoperiodic exposure and melatonin on embryo implantation and offspring growth were examined. Long photoperiodic exposure (18:6 h light:dark) was selected to resemble light pollution. Melatonin (10, 10, 10, 10 M) was added to the drinking water of mice starting at Day 1 (vaginal plugs) until delivery.

RESULTS

Melatonin treatment (10,10 M) significantly increased litter sizes compared to untreated controls (12.9 ± 0.40 and 12.2 ± 1.01 vs. 11.5 ± 0.43; P < 0.05). The most effective concentration of melatonin (10 M) was selected for further investigation. No remarkable differences were found between melatonin-treated mice and controls in terms of the pups' birth weights, weaning survival rates, and weaning weights. Long photoperiodic exposure significantly reduced the number of implantation sites in treated mice compared to controls (light/dark, 12/12 h), and melatonin rescued this negative effect. Mechanistic studies revealed that melatonin enhanced the serum 17β-estradiol (E) levels in the pregnant mice and upregulated the expression of the receptors MT1 and MT2 and p53 in uterine tissue. All of these factors may contribute to the beneficial effects of melatonin on embryo implantation in mice.

CONCLUSION

Melatonin treatment was associated with beneficial effects in pregnant mice, especially those subjected to long photoperiodic exposure. This was achieved by enhanced embryo implantation. At the molecular level, melatonin administration probably increases the E level during pregnancy and upregulates p53 expression by activating MT1/2 in the uterus. All of the changes may improve the microenvironment of the uterus and, thus, the outcomes of pregnancy.

摘要

背景

胚胎着床对动物繁殖至关重要。胚胎着床失败会导致妊娠失败,在人类辅助受孕中尤其如此。环境因素对胚胎着床有深远影响。由于人们夜间接触到更多光线,应探讨长期光照对胚胎着床的影响。

方法

研究了长光周期暴露和褪黑素对胚胎着床及后代生长的影响。选择长光周期暴露(18:6小时光照:黑暗)以模拟光污染。从第1天(阴道栓)开始,在小鼠饮用水中添加褪黑素(10、10、10、10微摩尔)直至分娩。

结果

与未处理的对照组相比,褪黑素处理组(10、10微摩尔)的窝产仔数显著增加(分别为12.9±0.40和12.2±1.01对11.5±0.43;P<0.05)。选择最有效的褪黑素浓度(10微摩尔)进行进一步研究。在仔鼠出生体重、断奶存活率和断奶体重方面,褪黑素处理组小鼠与对照组之间未发现显著差异。与对照组(光照/黑暗,12/12小时)相比,长光周期暴露显著降低了处理组小鼠的着床部位数量,而褪黑素挽救了这种负面影响。机制研究表明,褪黑素提高了妊娠小鼠血清17β-雌二醇(E)水平,并上调了子宫组织中MT1和MT2受体以及p53的表达。所有这些因素可能有助于褪黑素对小鼠胚胎着床的有益作用。

结论

褪黑素处理对妊娠小鼠有有益作用,尤其是对那些处于长光周期暴露的小鼠。这是通过增强胚胎着床实现的。在分子水平上,给予褪黑素可能会增加孕期E水平,并通过激活子宫中的MT1/2上调p53表达。所有这些变化可能会改善子宫微环境,从而改善妊娠结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/497b3c50a46b/12958_2017_297_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/28d5f9fd9dc3/12958_2017_297_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/378f0b917aba/12958_2017_297_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/ce4cbc8bc66a/12958_2017_297_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/497b3c50a46b/12958_2017_297_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/28d5f9fd9dc3/12958_2017_297_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/378f0b917aba/12958_2017_297_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/ce4cbc8bc66a/12958_2017_297_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d437/5625829/497b3c50a46b/12958_2017_297_Fig4_HTML.jpg

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