Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2
Abstract Background Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decli...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-022-03061-1 |
| _version_ | 1828293848696094720 |
|---|---|
| author | Se-Ra Park Seong-Kwan Kim Soo-Rim Kim Wook-Joon Yu Seung-Jin Lee Hwa-Yong Lee |
| author_facet | Se-Ra Park Seong-Kwan Kim Soo-Rim Kim Wook-Joon Yu Seung-Jin Lee Hwa-Yong Lee |
| author_sort | Se-Ra Park |
| collection | DOAJ |
| description | Abstract Background Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decline in female fertility and increased rate of spontaneous abortion could be associated with increased smoking rates. Indeed, women that smoked for 10 years or more were reported to have a ~ 20% higher infertility rate than women that had never smoked. However, the reasons for the underlying harmful aspects of smoking on female fertility remain a matter of debate. Importantly, a previous study revealed that resident endometrial stem cell deficiency significantly limits the cyclic regeneration potential of endometrium, which, in turn, decreases successful pregnancy outcomes. In this context, we postulated that exposure to mainstream cigarette smoke extracts might decrease female fertility by inhibiting the functions of resident endometrial stem cells. Methods We investigated whether cigarette mainstream smoke exposure directly inhibits various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, pluripotency, and differentiation capacity in vitro. Next, we determined whether SERPINB2 mediates cigarette smoke-induced suppressive effects on various tissue regeneration-associated functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. Mice were injected intraperitoneally with low (0.5 mg/kg) or high (1 mg/kg) doses of cigarette smoke extract (10 times for two weeks), and endometrial stem cells were then isolated from mice uterine tissues. Results We found that exposure to cigarette smoke extracts remarkably suppressed various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, multilineage differentiation ability, and pluripotency in vitro and in vivo by activating the SERPINB2 gene. Indeed, cigarette smoke-induced inhibitory effects on various endometrial stem cell functions were significantly abolished by SERPINB2 knockdown. Conclusions These findings provide valuable information on the harmful effects of cigarette smoking on resident endometrial stem cells and hopefully will facilitate the developments of promising therapeutic strategies for subfertile or infertile women that smoke cigarettes. |
| first_indexed | 2024-04-13T11:28:11Z |
| format | Article |
| id | doaj.art-0966814bfaf3442092e51d0002c67d87 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T11:28:11Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-0966814bfaf3442092e51d0002c67d872022-12-22T02:48:38ZengBMCStem Cell Research & Therapy1757-65122022-08-0113112010.1186/s13287-022-03061-1Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2Se-Ra Park0Seong-Kwan Kim1Soo-Rim Kim2Wook-Joon Yu3Seung-Jin Lee4Hwa-Yong Lee5Department of Health Sciences and Technology, GAIHST, Gachon UniversityDepartment of Health Sciences and Technology, GAIHST, Gachon UniversityDepartment of Health Sciences and Technology, GAIHST, Gachon UniversityDevelopmental and Reproductivoxicology Research Group, Korea Institute of ToxicologyDevelopmental and Reproductivoxicology Research Group, Korea Institute of ToxicologyDivision of Science Education, Kangwon National UniversityAbstract Background Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decline in female fertility and increased rate of spontaneous abortion could be associated with increased smoking rates. Indeed, women that smoked for 10 years or more were reported to have a ~ 20% higher infertility rate than women that had never smoked. However, the reasons for the underlying harmful aspects of smoking on female fertility remain a matter of debate. Importantly, a previous study revealed that resident endometrial stem cell deficiency significantly limits the cyclic regeneration potential of endometrium, which, in turn, decreases successful pregnancy outcomes. In this context, we postulated that exposure to mainstream cigarette smoke extracts might decrease female fertility by inhibiting the functions of resident endometrial stem cells. Methods We investigated whether cigarette mainstream smoke exposure directly inhibits various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, pluripotency, and differentiation capacity in vitro. Next, we determined whether SERPINB2 mediates cigarette smoke-induced suppressive effects on various tissue regeneration-associated functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. Mice were injected intraperitoneally with low (0.5 mg/kg) or high (1 mg/kg) doses of cigarette smoke extract (10 times for two weeks), and endometrial stem cells were then isolated from mice uterine tissues. Results We found that exposure to cigarette smoke extracts remarkably suppressed various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, multilineage differentiation ability, and pluripotency in vitro and in vivo by activating the SERPINB2 gene. Indeed, cigarette smoke-induced inhibitory effects on various endometrial stem cell functions were significantly abolished by SERPINB2 knockdown. Conclusions These findings provide valuable information on the harmful effects of cigarette smoking on resident endometrial stem cells and hopefully will facilitate the developments of promising therapeutic strategies for subfertile or infertile women that smoke cigarettes.https://doi.org/10.1186/s13287-022-03061-1SmokingEndometriumStem cellsInfertilitySelf-renewalMultilineage differentiation |
| spellingShingle | Se-Ra Park Seong-Kwan Kim Soo-Rim Kim Wook-Joon Yu Seung-Jin Lee Hwa-Yong Lee Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 Stem Cell Research & Therapy Smoking Endometrium Stem cells Infertility Self-renewal Multilineage differentiation |
| title | Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 |
| title_full | Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 |
| title_fullStr | Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 |
| title_full_unstemmed | Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 |
| title_short | Effects of smoking on the tissue regeneration-associated functions of human endometrial stem cells via a novel target gene SERPINB2 |
| title_sort | effects of smoking on the tissue regeneration associated functions of human endometrial stem cells via a novel target gene serpinb2 |
| topic | Smoking Endometrium Stem cells Infertility Self-renewal Multilineage differentiation |
| url | https://doi.org/10.1186/s13287-022-03061-1 |
| work_keys_str_mv | AT serapark effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 AT seongkwankim effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 AT soorimkim effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 AT wookjoonyu effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 AT seungjinlee effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 AT hwayonglee effectsofsmokingonthetissueregenerationassociatedfunctionsofhumanendometrialstemcellsviaanoveltargetgeneserpinb2 |