Uterine pinopodes in peri-implantation human endometrium. Clinical relevance.

Current clinical studies indicate the existence in the human of an "implantation/nidation window," similar to that observed in animal models. During this short period of uterine receptivity, the formation of pinopodes on the apical cell membrane of the endometrial epithelium is a consistent morphological event, observed in a number of species studies including the human. In order to develop a specific marker of the implantation window in clinical practice, we have investigated the kinetics of pinopode formation through sequential endometrial sampling under various hormonal conditions.

Endometrial corticotropin-releasing hormone: expression, regulation, and potential physiological implications.

Our findings show that human and rat uterus express the CRH gene. Epithelial cells of both species are the main source of endometrial CRH, while stroma does not seem to express it, unless it differentiates to decidua. Immunoreactive CRH, produced by endometrial cells, has the chromatographic characteristics of authentic hypothalamic CRH, while the size of its mRNA in both human and rat uterus is similar to or identical with its counterpart, present in placenta and hypothalamus (1.

Hormonal anti-implantation agents: antiprogestins.

Oestrogens and progestogens separately or in combination are able to prevent implantation with high efficiency, thus acting as interceptive agents. Current interceptive medical regimens include high-dose oestrogens, the association of oestrogens with progestogens or progestogens alone. Compounds with antiprogesterone properties, such as RU 486 (mifepristone) or ZK 98734 (lilopristone), also exhibit a strong interceptive action which, as shown in animal models, is proportional to the dose and the day(s) of administration.

The role of prostaglandins in blastocyst implantation.

This review summarizes the information available on the involvement of prostaglandins in blastocyst implantation, and examines their interactions with three other inflammatory mediators, platelet-activating factor (PAF), interleukin (IL-1) and corticotrophin-releasing factor (CRF). Essential elements of this information, consistent with the assumption that prostaglandins play an important role in implantation, appear to be: (i) the burst of endometrial prostaglandin production, following the blastocyst signal(s) or an artificial stimulus; (ii) the main localization of this production at the luminal epithelium and release towards the stroma; and (iii) the presence at the stromal level of specific progesterone-dependent binding sites for prostaglandin E2. In addition, accumulated data indicate a paracrine interaction at the endometrial level between PAF and prostaglandin E2, which could serve, among others, to amplify the embryonic signal(s).

Uterine pinopodes as markers of the 'nidation window' in cycling women receiving exogenous oestradiol and progesterone.

In 14 cycling women participating in an in-vitro fertilization (IVF) donation programme, we examined the timing of the 'nidation window' using as a stage-specific 'marker' the presence of fully developed pinopodes on the apical surface of the luminal uterine epithelium. Each woman received exogenous oestradiol from the second day of their cycle and progesterone starting on day 8 or day 15 of the oestrogenic treatment. The women underwent two biopsies during the same artificial cycle, on either days 6 and 9 or days 8 and 10 of the progesterone treatment.

Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus.

We have shown previously that the epithelial cells of human endometrium produce CRH. The biological role of endometrial CRH is not yet known. Among other things, CRH appears to be involved in the inflammatory process, acting as an autocrine/paracrine proinflammatory regulator.

The zona reaction in human oocytes as seen with scanning electron microscopy.

Using scanning electron microscopy we found differences in the fine structure of the zona pellucida between unfertilized and fertilized human pronuclear stage oocytes in an in-vitro fertilization programme. In unfertilized oocytes, the zona pellucida appeared porous, comprising a large number of ring-shaped structures, called hoops, randomly superimposed in several layers. Superficial pores had a mean diameter of 4 microns, with the diameter decreasing in more inner lying pores.

Effects of cholic acid and 'Protectaid' formulations on human sperm motility and ultrastructure.

Cholic acid (sodium cholate) and the other active ingredients of F-5 gel preparations in use for the impregnation of a new vaginal sponge (Protectaid) with contraceptive and anti-sexually transmitted disease properties, were assessed for their effects on human sperm motility and ultrastructure. Cholic acid (CA) produced an inhibition of motility which was both dose- and time-dependent. A complete suppression of motility was obtained at 30 s by a CA concentration of 1.

Inhibition of progesterone receptor function results in loss of basic fibroblast growth factor expression and stromal cell proliferation during uterine remodelling in the pregnant rat.

Recent studies suggest that hormonal control of uterine cell proliferation may be moderated by polypeptide growth factors. It remains to be determined, however, whether growth factors cause or are the consequence of hormone action. Basic fibroblast growth factor (bFGF) has been shown to influence cell proliferation and differentiation of a variety of mesoderm-derived cells.

Physiological oestradiol and progesterone replacement cycles in women with ovarian failure: a model to study endometrial maturation and sex steroid receptor regulation by exogenous hormones.

High endometrial receptivity has been achieved with physiological oestradiol and progesterone replacement cycles in women with ovarian failure. To understand whether different protocols using the oral route or the transdermal route can influence the endometrial maturation and the regulation of sex steroid receptors, we studied 33 women with ovarian failure treated by two commonly used protocols and assessed endometrial receptivity using light microscopy, scanning electron microscopy and immunohistochemistry for oestrogen and progesterone receptors on biopsies taken to include different periods of the luteal phase. The morphology in these patients was similar to that observed in women with normal ovulatory cycles, indicating that the morphological response is not dependent on the type of oestradiol, oral or transdermal, in the replacement cycles as compared to the endogenous oestradiol in the menstrual cycle.

Spermicidal and antiviral properties of cholic acid: contraceptive efficacy of a new vaginal sponge (Protectaid) containing sodium cholate.

Cholic acid (sodium cholate) exhibits a strong spermicidal and antiviral [anti-human immunodeficiency virus (HIV)-1] activity. The same effects are observed for F-5 Gel, the active mixture of a new contraceptive sponge (Protectaid), which contains sodium cholate in association with low concentrations (0.5%) of nonoxynol-9 and benzalkonium chloride.

Preovulatory effects of the progesterone antagonist mifepristone (RU486) in mice.

The progesterone antagonist mifepristone (RU486), was given in mice once on different days of pregnant mare's serum gonadotrophin-human chorionic gonadotrophin (PMSG-HCG) treatment and its action upon the induction of ovulation studied. RU486 administered on the day after PMSG significantly reduced the ovulation rate. Ovulation was completely inhibited when the progesterone antagonist was given simultaneously with HCG, but RU486 administered 4 h after HCG treatment remained ineffective.

Hormonal dependence of pinopode formation at the uterine luminal surface.

The uterine luminal epithelium during the period of receptivity for nidation displays characteristic protrusions of the apical surface named pinopodes. The effects of oestradiol and progesterone, singly or in combination, on the formation and regression of pinopodes were investigated using scanning electron microscopy. The appearance of pinopodes was found to be strictly progesterone dependent.

Is cholic acid responsible for embryo-toxicity of the post-receptive uterine environment?

HPLC analysis of the embryo-toxic fraction of human uterine fluid, collected between the 22nd and 25th days of the menstrual cycle, revealed the presence of cholic acid at high concentrations. It is suggested that cholic acid could be responsible for the embryo-toxicity of the uterine environment, which follows the receptive period for implantation.

Hormonal dependence of the metrial gland: further studies on oestradiol and progesterone receptor levels in the rat.

The main objective of the present study was to analyse the hormonal dependence of the metrial gland formed in pseudopregnant animals following massive decidualization. On day 13 of pseudopregnancy (when the metrial gland reaches its maximal development) animals were ovariectomized and given s.c.

Effect of mifepristone (RU 486) on concentrations of prostaglandin E-2 binding sites in the rat endometrium.

Progesterone implants in ovariectomized rats increased endometrial concentrations of PGE-2 receptors. The increase was completely inhibited by simultaneous daily injection (7.5 mg/kg) of mifepristone (RU 486).

Displacement of receptivity for nidation in the rat by the progesterone antagonist RU 486: a scanning electron microscopy study.

In the rat, the period of receptivity for nidation (implantation window) is characterized by specific change of the apical surface of the luminal uterine epithelium, such as the presence of large ectoplasmic projections (pinopodes). Under the conditions of this study, fully developed pinopodes appeared during normal pseudopregnancy on day 5 only. When RU 486 (5 mg/kg s.

Scanning electron microscopy of postovulatory human endometrium in spontaneous cycles and cycles stimulated by hormone treatment.

The ultrastructure of the luminal surface epithelium was compared in endometrial samples taken from 23 normally cycling women and from 22 patients submitted to ovarian stimulation with clomiphene citrate (100 mg/day for 5 days), human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). On day 2 after ovulation, only four out of nine specimens taken from the women in the hormone-treated group were identical to those of normally cycling women. On day 6 after ovulation, only two out of the 13 biopsy specimens from the treated group were the same as those from normally cycling women at that stage.

Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486.

RU 486 was administered to rats on Day 1 or Days 1 + 2 of pregnancy. Endometrial sensitivity (i.e.

Influence of the embryo on the distribution of maternal immunoglobulins in the mouse uterus.

The effect of the embryo on the distribution of IgA, IgG and IgM was studied by an immunoperoxidase technique on mouse uterine sections, (1) during the first part of pregnancy and pseudopregnancy, and (2) in delayed implantation combined with different progesterone-oestradiol treatments designed to extend the delay or induce implantation, and in nonpregnant ovariectomized mice similarly treated. The number of glandular lumina containing IgA increased particularly from the implantation period, but in pseudopregnancy this number decreased from the morning of Day 4, and afterwards continued to decline. In delayed implantation, the number of glandular lumina containing IgA also rose considerably when implantation was induced by oestradiol, whereas under the same progesterone-oestradiol treatment, nonpregnant ovariectomized animals displayed no such increase.