An Intronic SINE at Pou5f1 Links Hormone Signaling to Blastocyst Hatching
Year: 2026
Type: preprint
Abstract: Before implantation, mammalian embryos must escape from the zona pellucida, a protective glycoprotein coat that surrounds the blastocyst. This process, known as hatching, is essential for uterine attachment and has been viewed largely as a mechanical consequence of blastocyst expansion and zona weakening. Whether hatching is actively timed by embryo-intrinsic gene regulation remains unclear. Here we show that timely hatching of mouse embryos requires signal-responsive repression of Pou5f1/OCT4 in the trophectoderm by a single intronic B2 short interspersed nuclear element. Deleting this element preserves blastocyst formation and stem-cell competence, but disrupts trophectodermal OCT4 repression, delays zona escape, causes hatching-uterine receptivity mismatch, perturbs implantation-site organization and reduces peri-implantation fitness. CRISPR activation screening, siRNA and pharmacological perturbation, and defined progesterone/estradiol/EGF culture conditions identify an ESRRA-linked endocrine/growth-factor response that requires the B2 element to consolidate trophectoderm maturation. Comparative analyses further show that young intronic SINEs are enriched in developmental gene programs, whereas human POU5F1 intronic Alu elements exhibit genetic constraint and repressive potential. These findings identify intronic SINEs as molecular entry points that couple extracellular cues to lineage-restricted transcriptional control and morphogenic transition.
Authors: Youjia Zach Guo, Hyun Hyung An, Katelyn Toohill, Sneha Ramesh Mani, Ten D Li, Chantal Diallo, Diego Antonio Jimenez, Alyssa Saito, Nicolae Adrian Leu, Beril Tore, Jamie Yoon Ha, Vamshidhar Nallamala, Sarah Stanger, Piotr Tetlak, Yanlin Hou, Ana Domingo-Meulas, Nicolas D Plachta, Monica Ailawadi Mainigi, Andrew J Modzelewski
Institution: University of Pennsylvania
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204234382