{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:04:20Z","timestamp":1791561860783,"version":"4.3.4"},"reference-count":24,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2021,1,6]]},"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The zona pellucida (ZP) of human oocytes plays essential protective roles in sperm\u2013egg interactions during fertilisation and embryo development.\n                      <jats:italic>ZP4<\/jats:italic>\n                      -null female rabbits exhibit a thin and irregular ZP, which severely impairs embryo development and fertility. However, the effects of\n                      <jats:italic>ZP4<\/jats:italic>\n                      defect on human female reproduction remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We performed whole-exome sequencing in 26 female patients with abnormal (thin and irregular) ZP and identified heterozygous variants in\n                      <jats:italic>ZP4<\/jats:italic>\n                      (OMIM: 613514) from 3 patients (approximately 11%). No\n                      <jats:italic>ZP4<\/jats:italic>\n                      variant was found in the 30 control women with proven fertility. We constructed\n                      <jats:italic>ZP4-<\/jats:italic>\n                      mutated plasmids and found that the variants reduced the secretion of ZP4 in vitro. Lower suction pressure facilitated egg retrieval, and intracytoplasmic sperm injection (ICSI) was a desirable treatment for\n                      <jats:italic>ZP4-<\/jats:italic>\n                      mutated patients with abnormal ZP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>ZP4<\/jats:italic>\n                      as a novel gene for human abnormal ZP and found that lower suction pressure and ICSI are efficient treatment strategies.\n                    <\/jats:p>\n                  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