{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:21:47Z","timestamp":1767846107504,"version":"3.49.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T00:00:00Z","timestamp":1573948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1000200"],"award-info":[{"award-number":["2016YFC1000200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Major Project of the Ministry of Science and Technology of Hunan Province, China","award":["2017SK1032"],"award-info":[{"award-number":["2017SK1032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Empty follicle syndrome (EFS) is the complete failure to retrieve oocytes after ovarian stimulation. Although LHCGR and ZP3 were identified as causative genes, it is still unclear what happens to these patients\u2019 oocytes, and the pathogenesis of EFS remains obscure. Here, we identified six novel ZP1 mutations associated with EFS and female infertility that was inherited recessively in five unrelated families. Studies in CHO-K1 cells showed that these mutations resulted in either degradation or truncation of ZP1 protein. Immunohistochemistry using ovarian serial sections demonstrated that all preantral follicles had normal architecture, but with a thin ZP, lacking ZP1, surrounding the growing oocytes. The antral follicles were also defective in normal cumulus\u2013oocyte complex organisation, leading us to speculate that the lack of ZP1 might lead to oocyte degeneration or increased fragility of the oocyte during follicular puncture, ultimately resulting in EFS. To our knowledge, this is the first study that presents morphological evidence showing normal preantral folliculogenesis with abnormal ZP assembly in EFS patients. Our data provides a better understanding of the biological functions of ZP1 in human ZP assembly and folliculogenesis and gives new insights into the pathogenesis of EFS and possible therapeutic developments.<\/jats:p>","DOI":"10.1093\/humrep\/dez174","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T04:38:57Z","timestamp":1564115937000},"source":"Crossref","is-referenced-by-count":13,"title":["ZP1 mutations are associated with empty follicle syndrome: evidence for the existence of an intact oocyte and a zona pellucida in follicles up to the early antral stage. A case report."],"prefix":"10.1093","author":[{"given":"Can","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Basic Medicine, School of Medicine, Hunan Normal University, No. 371 Tongzipo Road, Changsha 410013, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"National Engineering and Research Center of Human Stem Cell, No. 8 Luyun Road, Changsha 410205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Gong","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine, Hunan Normal University, No. 371 Tongzipo Road, Changsha 410013, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changfu","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueren","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine, Hunan Normal University, No. 371 Tongzipo Road, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangxiu","family":"Lu","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"National Engineering and Research Center of Human Stem Cell, No. 8 Luyun Road, Changsha 410205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"Reproductive and Genetic Hospital of CITIC-Xiangya, No. 84 Xiangya Road, Changsha 410008, China"},{"name":"Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, No. 88 Xiangya Road, Changsha 410008, China"},{"name":"National Engineering and Research Center of Human Stem Cell, No. 8 Luyun Road, Changsha 410205, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,17]]},"reference":[{"key":"2019111622401114900_ref1","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1093\/humrep\/dey215","article-title":"Novel homozygous nonsense mutations in LHCGR lead to empty follicle syndrome and 46, XY 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