Inhibitory influence of uterine secretions on mouse blastocysts decreases at the time of blastocyst activation

Abstract

Uterine flushings from artificially 'pseudopregnant', pseudopregnant and pregnant mice and those with 'diapausing' embryos were tested for their effect on [3H]uridine incorporation by mouse blastocysts. An inhibitor of [3H]uridine incorporation was detected in the uterine fluid of the mice with diapausing embryos and the activity of the inhibitor was significantly reduced 6.25 h after an injection of oestrogen. This reduction of the inhibitory activity was dependent on the presence of blastocysts in utero, since a similar reduction did not occur in uterine fluids of pseudopregnant mice. The results support the suggestion that 'delayed' implantation in mice is caused by the presence of inhibitors of blastocyst metabolism and that activation, after an increase in oestradiol, is due to an embryo-dependent loss of activity of the inhibitors.

Patterns of protein synthesis in endometrial tissues from ovariectomized rats treated with oestradiol and progesterone

“…Therefore, our results tend to contradict the proposition that blastocyst activation depends on the production of a molecule which inactivates inhibitory proteins (Weitlauf, 1976). Such a factor, however, might originate from the embryos themselves (O'Neill & Quinn, 1981, 1983. In a recent study using bidimensional mapping it was found that in the endometrium of preg¬ nant rats killed at the time of implantation (Day 5) no unique protein appears while several pep¬ tides are no longer synthesized (Mulholland & Villee, 1984).…”

“…Supporting the first hypothesis are the increased uterine RNA and general protein synthesis on Day 5 (Heald, 1976), the induction of implantation by uterine RNA extracts (Segal, Scher & Ko'ide, 1977 ; Lejeune, Puis¬ sant, Camus & Leroy, 1982b) and the secretion into the uterine lumen of specific proteins at Day 5 (Surani, 1977). On the other hand, stimulation of implantation by actinomycin D (Finn, 1974;Camus, Lejeune & Leroy, 1979) as well as the inhibitory influence on blastocysts of fluids from uteri of animals with delayed implantation (Psychoyos, 1973;Weitlauf, 1976Weitlauf, , 1978O'Neill & Quinn, 1981, 1983, stand in favour of a mechanism acting through release from inhibition. In rats and mice, implantation depends on a sequence of ovarian secretions (oestrogen, proges¬…”

Embryo development and zona-shedding in the ligated oviduct and contralateral uterine horn of non-lactating and lactating Mongolian gerbils (Meriones unguiculatus)

“…There is a significant increase in oestrogen-dependent, intraluminal uterine protein before zona-shedding in the gerbil (Norris, 1979). In the mouse, this secretion is thought to stimulate the blastocyst to overcome the effects of the putative inhibitor (O'Neill & Quinn, 1983), or to dissipate the effect of the inhibitor (Camus, Lejeune & Leroy, 1979). An interplay of inhibitory and stimulatory factors is possible, and indeed may be necessary and compatible for a full explanation (Mintz, 1970;Weitlauf & Kiessling, 1981).…”

Effects of metabolic substrates and ionic environment on in-vitro activation of delayed implanting mouse blastocysts

“…It now seems unlikely that changes in the availability of organic substrates or ionic environment in the uterine lumen are the controlling factor in initiation of metabolic activation. An alternative explanation may be the presence of inhibitory substances in the uterus during delayed implantation which are removed after administration of oestrogen or by transfer of embryos to an in-vitro environment (Psychoyos, Bitton-Casimiri & Brun, 1975;Weitlauf, 1976;O'Neill & Quinn, 1983). This possibility is being explored.…”