Correlation of pinopod development on uterine luminal epithelial surface with hormonal events and endometrial sensitivity in rat

Abstract

Intrinsic role of preovulatory and nidatory estrogen and progesterone and presence of viable blastocysts in utero in pinopod development on the uterine luminal epithelial surface and correlation between time of their development and onset of endometrial sensitivity were investigated. In adult rats, pinopods were observed on the entire epithelium even before secretion of nidatory estrogen, i.e. at 14.00 h on day 4 post-coitum (p.c.). Apparently, their number increased, more so on the antimesometrial than the mesometrial side, at 10.00 h on day 5, but were fewer and mostly collapsed at 10.00 h on day 6. Pinopods on day 4 were located within epithelial depressions and foldings, but protruded from the surface on days 5 and 6. Normal pinopods were also present on day 8 p.c. in rats under delayed implantation, but an implantation-inducing dose of estradiol-17 beta administered about 18 h earlier caused their collapse like that on day 6 in intact rats. Development and appearance of pinopods in intact or delayed rats was unaffected when native preimplantation embryos were prevented from entering the uterus. Normal pinopods were seen in immature rats receiving progesterone for at least 3 days or cyproterone acetate for 4 days, but not after estradiol alone. In animals receiving progesterone or priming/sensitizing estradiol in addition to progesterone, the decidual response was suboptimal, irrespective of the presence of pinopods on the day of stimulation. In animals in which a condition mimicking preimplantation had been produced by suitable hormone supplementation, optimal endometrial sensitivity and decidual response were elicited, even though most pinopods appeared collapsed, resembling those on day 6 in intact rats and about 18 h after estradiol in implantation-delayed rats. Findings confirm that pinopod development on uterine luminal epithelium was dependent on progesterone alone and demonstrate that: (i) preovulatory (priming) or nidatory (endometrial sensitizing) estrogen or viable blastocysts in utero have no role in their development. Nidatory estrogen, instead, appears to limit pinopod development by causing their collapse; (ii) pinopod development/presence on the endometrial surface might indicate the uterus coming into a period of sensitivity rather than actually being in it and might thus serve as a useful marker of "transfer window" rather than "implantation window"; (iii) in the rat, pinopod development might serve as an alternate assay for evaluation of progestational activity of newer test agents.

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

“…In the rat, pinopods appear on the antimesometrial segment of the uterus in the presensitivity period, and their numbers increase to a maximum on day-5 postcoitus (pc), coinciding with a period of maximum endometrial receptivity in this species (Bansode et al, 1998). Pinopods are located within epithelial depressions on day-4 pc but protrude from the surface by days 5 and 6 (Singh et al, 1996). Pinopods were shown to mediate epithelial uptake of fluid (Enders and Nelson, 1973) and macromol- Fig.…”

“…We speculated that changes might be observed at the level of subcellular organelles. One such structure, the pinopods, are smooth apical membrane projections of the epithelial cells that appear at the time of implantation in all mammalian species studied so far (Guillomot et al, 1986;Edwards, 1994;Nikas et al, 1995;Singh et al, 1996;Kolb et al, 1997;Bansode et al, 1998;GarciaVelasco et al, 1998) Pinopods are perhaps a more sensitive marker of the window of implantation than histology or any currently characterized molecular marker. We reasoned that Hoxa10 may be necessary for pinopod formation and, thereby, enhance uterine receptivity.…”

Molecular determinants of uterine receptivity

“…Pinopod number increases on day 4 of pregnancy and becomes more abundant on day 5 when the uterus enters the receptive phase in rats (Psychoyos and Mandon, 1971). During the postimplantation period, pinopod number decreases rapidly (Singh et al, 1996). This developmental change of pinopods in the uterus is highly progesterone dependent, while administration of high doses of estradiol abolishes the pinopod (Martel et al, 1991), highlighting the similarity of hormonal conditioning for pinopod formation with the attainment of uterine receptivity.…”

Progesterone receptor gene expression in preimplantation pig embryos

“…Progesterone, an ovarian steroid traditionally regarded as the primary mammalian pregnancy hormone, serves to coordinate a complex series of interactive steps, beginning with the synchronized development of the preimplantation embryo and maternal uterus and ending with implantation (1,2). The elimination of progesterone from pregnant animals has deleterious effects on embryonic development and implantation (3). The physiological effects of progesterone are known to be mediated initially by a specific intracellular protein referred to as a progesterone receptor (PR) (4).…”