MUMBAI, Nov. 17 -- Indian scientists have identified a genetic "switch" inside the uterus that allows an embryo to implant itself, signalling the start of pregnancy. The study, published in the online research journal 'Cell Death Discovery' on November 10, is the first to map how two genes work like opposing levers, one opening the uterine lining and the other closing it, to ensure that pregnancy begins at precisely the right moment. The research, led by Dr Deepak Modi of ICMR-National Institute for Research in Reproductive and Child Health (NIRRCH), Mumbai, shows how the genes, HOXA10 and TWIST2, act as a coordinated system that either seals the uterine wall or softens it briefly to let an embryo embed itself. Other participants in the study which combined molecular biology, genomics, and computational modelling were Dr Shruti Hansda of Banaras Hindu University, Professor Mohit Jolly from IISc Bengaluru, and Nancy Ashary, a student and the first author of the paper. "For pregnancy to happen, there is a gene in the uterus that has to switch off and another that needs to switch on," Modi explained. "When the uterine wall needs to stay protected, HOXA10 switches on. But when the embryo arrives, HOXA10 must switch off at that spot, and TWIST2 switches on to open the gate." The team demonstrated this switch in mice, hamsters, monkeys, and human tissues, underscoring that it was a deeply conserved evolutionary mechanism acquired millions of years ago. The work took eight years, largely because obtaining human uterine tissue at the exact window of implantation is extremely challenging. Modi said, "People across the world have not been able to study what happens right at the point where the uterine wall has to open." The team therefore recreated the process in cell lines and used animal models. Blocking TWIST2 in mice resulted in failed implantation, proving that the genetic switch is indispensable. Mathematical modelling from IISc Bengaluru confirmed that the HOXA10-TWIST2 pair behaves as a self-regulating, tightly timed switch. The findings could reshape infertility diagnostics. "Now we understand why some women don't conceive even when embryos are healthy," Modi said. "If the switches aren't operating correctly, if HOXA10 doesn't turn off or TWIST2 doesn't turn on, implantation simply won't happen." According to him, this opens up three major avenues for fertility care. One, doctors could use uterine tissue or endometrial biopsies to check whether the HOXA10-TWIST2 switch is functioning.Two, clinics could develop biomarkers that track TWIST2 activation or HOXA10 suppression to pinpoint the most receptive implantation window. The third avenue, said Modi, was new targets for drug development....