The cell biological basis of human implantation John D. Aplin* MA, PhD Academic Unit of Obstetrics and Gynaecology, School of Medicine and School of Biological Sciences, University of Manchester, UK Understanding the cellular basis of implantation and placental development depends on a combination of the limited morphological evidence in the human with data from other primates, separate studies of pre-implantation embryos and endometrium and in vitro models. There is increasing evidence of a dialogue between embryo and endometrium that begins prior to implantation and evolves rapidly through the successive epithelial and stromal/ vascular phases. This includes paracrine signals passing to endometrial tissue from the embryo, and vice versa. The production and timing of these signals by endometrium, and its ability to respond to signals from the blastocyst, are dependent on steroidal sensitization. A complex cascade of cell adhesion mechanisms and local tissue remodelling are required for the establishment of a stable haemochorial interface. Key words: embryo; endometrium; implantation; trophoblast; placenta. Implantation depends on the synchronization of two biological clocks. The maternal clock begins eectively at ovulation when steroid production in the ovary switches from oestrogen to progesterone plus oestrogen (see Sunder and Lenton, Chapter 4). Acting through receptors in stromal, epithelial and vascular cells 1±4 , progesterone causes the endometrium to dierentiate such that it reaches a state of readiness for implantation approximately 7 days after the luteinizing hormone peak, or 5.5 days after ovulation. 5 Some 24 hours after ovulation, at fertilization, the embryonic clock is set, pro- gressing through cleavage and compaction stages to produce a blastocyst, the result of cell dierentiation into inner cell mass (ICM) and trophectodermal (TE) derivatives. TE cells are positioned at the outer boundary of the embryo, and are responsible for its attachment to endometrium. Later, TE gives rise to several trophoblast lineages that combine with extra-embryonic mesenchyme to form the placenta. The ICM acts as the precursor of all true embryonic and fetal tissues. After the blastocyst has hatched from its zona pellucida, TE becomes attached to the maternal luminal epithelium, most frequently at the upper posterior uterine wall. The embryo then rapidly proceeds to penetrate the epithelium and subjacent basement membrane, becoming embedded in maternal stroma. Re-epithelialization covers over the site of intrusion. This epithelial phase of implantation is complete by 6±7 days after ovulation. 6,7 1521±6934/00/050757+08 $35.00/00 * c 2000 Harcourt Publishers Ltd. BaillieÁre's Clinical Obstetrics and Gynaecology Vol. 14, No. 5, pp. 757±764, 2000 doi:10.1053/beog.2000.0116, available online at http://www.idealibrary.com on 1 * Address for correspondence: Research Floor, St Mary's Hospital, Manchester M13 0JH, UK.