A sequence of events in the uterus prior to implantation in the mouse

Abstract

I reviewed a series of events in the mouse uterus before implantation on Day 4 of pregnancy (the sperm positive day is counted as Day 1). Major events are spacing of embryos along the uterine horns, shedding of the zona pellucida, and closure of the uterine lumen. How subtle they may be, there appear to exist interactions between intrauterine blastocysts and the uterus which is regulated by ovarian steroids. Spacing of embryos along the uterine horn is not random, but they are rather evenly distributed along the entire horn. The mechanism of even distribution of embryos needs clarification, although studies indicate that adrenergic nerve activity, prostaglandins, and other molecules appear to be involved. Shedding of the zona pellucida involves trypsin-like proteinase lysis of the zona. Through the opening created by zona lysis, blastocyst gets out of the zona by repeating expansioncollapse movements. Closure of rat uterine lumen is reported to be the result of absorption of uterine fluid through uterine glands. This needs to be confirmed in other species of rodents. Since these events influence blastocyst implantation, we need more detailed information on their regulatory mechanisms in order to improve the rate of healthy implantation of transferred embryo. Keywords Embryo spacing . Zona shedding . Luminal closure Leonov at LHRRBWhen our group with Roy O. Greep and John Biggers' group were sharing the 4th floor of the Laboratory of Human Reproduction and Reproductive Biology (LHRRB) building at Harvard Medical School, I heard a rumor that FBI agents were on the floor and they were setting telephone line taps.-It was still the time when the relationship between the U.S. and USSR was not friendly. Soon we learned that Boris Leonov, a Russian scientist, was coming to work in Biggers' laboratory. Leonov was from the All-Union Scientific Institute of Obstetrics and Gynecology, Moscow. He found prostaglandins (PGs) are involved in mammalian embryonic development and came to work with John Biggers. Leonov's work with John demonstrated that endogenous PGs are involved in blastocyst expansion and may play a role in implantation [1].A series of heavy snow falls buried the Boston area last winter. We also had similar heavy snow falls in the winter of 1977-8. After a very heavy snow fall in that winter I walked along Brookline Avenue to the medical school area to take pictures of the "snowscapes" at Harvard Medical School. While I was taking some pictures on Shattuck Street, I saw Leonov came along and greeted each other, and it was my last chance to see Boris Leonov. Some years after Leonov left LHRRB, Racowsky and Biggers published a paper on PG using mouse and rabbit embryos [33]. They found strong evidence for PG synthesis by rabbit blastocyst, but not by the mouse.For the celebration issue for John Biggers' 90th birthday and his accomplishment, I have chosen to write a review of the chronological events between pre-implantation embryonic development and implantation, hopefully to fill the gap between John's r...

Insights from imaging the implanting embryo and the uterine environment in three-dimensions

“…3C). Luminal closure ensues at GD4.25 to lock the embryo into position (Chen et al, 2013;Yoshinaga, 2013). Concomitant with closure, we observed that the lumen flanking the embryo, the peri-implantation region, becomes entirely devoid of folds in the M-AM axis; folds also grow more shallow along the oviductal-cervical axis, while folding along the M-AM axis is retained in the inter-implantation region ( Fig.…”

Continuous model of conceptus implantation to the maternal endometrium

“…These processes are followed by placental formation. During phase 1, the fertilized egg/ blastocyst enters and migrates within the uterus and may become affixed evenly at any point along the uterine horn in murine and porcine species (Yoshinaga 2013). Hatching allows the expansion of the blastocyst into a sphere or it may migrate and go through changes in its shape from spherical to tubular and filamentous form, as in domestic animals.…”

Embryo implantation triggers dynamic spatiotemporal expression of the basement membrane toolkit during uterine reprogramming

“…In mice, endometrium epithelial and mesenchymal cell behaviors are altered upon the initiation of pregnancy through ovarian-derived hormones and cellular compartment cross-talk [47–50]. By day 4 of the 21-day term of pregnancy in mice, the uterus is conducive to blastocyst implantation and decidualization is triggered upon embryo attachment [51–53].…”