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[Nidation in the Triton W.R. 1339 treated mouse: effect of progesterone and estradiol].

In the mouse injection of 800 mg/kg of Triton W.R. 1339 during the first four days of gestation prevents nidation. Examination of the uterine horns between days 6-12 reveals that a daily injection of 5 mg progesterone up from day 1 of gestation assures the survival of the blastocysts in Triton W.R. 1339 treated females and determines a delayed nidation. Nidations occur only after injection of 0.1 microgram of oestradiol benzoate at the beginning of the 5th day.

Animals↗

Evidence of a specific nidation site in ruminants.

The site of umbilical cord attachment in ruminants indicates the limited segment of the uterus where the blastocyst attachment occurs and could have potential significance for locating presumptive nidation sites. Measurements of the site of cord attachment were made on impala (Aepyceros melampus) and common duiker (Sylvicapra grimmia) at several stages of gestation. Both implant only in the right uterine horn although they ovulate from either ovary. Relative to uterine length, cord attachment in impala is somewhat closer to the cervix than it is in common duiker. As pregnancy advances in common duiker, the relative position of cord attachment becomes closer to the tubal end. This relationship was not seen in impala and may perhaps to be attributed inadequate data. Upon extrapolation of the data from common duiker, a presumptive attachment area is suggested for this species. This region is located at about 41% of the distance from the internal cervical os to the uterotubal junction. Similar cord attachment data could be used in any ruminant species to indicate the existence and location of a specific nidation site.

Animals↗

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. All patients to whom oestradiol was administered for 7 days prior to progesterone administration (n = 9), and two of the five treated with oestradiol for 14 days prior to the addition of progesterone, showed uterine pinopodes in either one or both biopsies. When present on a given day, pinopodes were at the same stage, developing, fully developed or regressing, showing that their total lifespan did not exceed 48 h. Fully developed pinopodes existed for 1 day only which may correspond to the short period of optimal endometrial receptivity observed in animal models. The timing of the presence of fully developed pinopodes varied from patient to patient, but these individual differences were not correlated with progesterone and oestradiol plasma concentrations. The brief duration of the nidation window and the observed individual variations in its timing suggest that the detection of uterine pinopodes could be a valuable tool for the prediction, on an individual basis, of the optimal date for successful egg replacement in IVF patients.

Adult↗

[Effect of different estro-progesterone sequences on nidation of dormant blastocysts administered in diapause in ovariectomized rats].

The hormonal condition permitting delayed nidation in rats ovarectomized on day 4 or 5 of pregnancy was studied by administering progesterone and estradiol in differents sequences between days 9 and 14. The best result was obtained when progesterone was given 3 days before an estrogen-progesterone association. The same treatment induced delayed nidation in rats receiving Reserpine and ovariectomized day 5, but not when progesterone and estradiol were present day 4.

Animals↗

Electron microscopic studies on the endometrium of the grey seal (Halichoerus grypus) during its preparation for nidation.

The uterine luminal and glandular epithelia of two mature grey seals, a species with obligate delayed implantation, have been examined. Earlier studies of their corpora lutea had suggested that these females were in the pre-nidatory condition. Ultrastructural features of these epithelia in the animal which possessed the more mature corpus luteum indicated that the luminal epithelium had attained a state of differentiation similar to that of the pre-attachment phase in the laboratory rat, a state known to be compatible with nidation. The animal with the less well developed corpus luteum demonstrated the early stages of the early endometrial response to progesterone (the hormone which takes the uterus out of the delay condition). In the grey seal, despite the late start, a similar sequence of morphological changes to those present in the endometrium of normally implanting animals occurs. Thus, it seems that in the majority of eutherian mammals, endometrial preparation for nidation follows a relatively standard pattern, and occurs pari passu with the differentiation of the luteal tissue.

Animals↗

Nidation inhibition by simple ergoline derivatives.

The ability of four ergoline-type compounds (elymoclavine, its O-benzoate and O-carbamate, and N-methyl-6,7-secoelymoclavine) to inhibit nidation in rats was determined and found to parallel their prolactin-inhibiting activity.

Animals↗

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.c.) was given once on day 1, the chronological limits of the appearance of these projections were changed. Fully formed pinopodes were observed on days 6-8 instead of day 5, indicating a displacement and enlargement of the receptive period. This property of the progesterone antagonist could be of clinical interest if it could be used to enlarge the 'implantation window' in women after replacement of in-vitro fertilized eggs.

Animals↗

Effects of progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of nidation, and termination of pregnancy in bonnet monkeys.

The effects of a progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of implantation or pregnancy, and termination of early and mid-pregnancy were studied in bonnet monkeys. In the regularly menstruating animals, administration of lilopristone (25 mg/day, s.c.) during the mid-luteal phase (Days 20-22 of the menstrual cycle) induced menstruation within 2-4 days after the initiation of treatment. A premature drop in circulating progesterone levels was also observed. The luteolytic effect of lilopristone was prevented by exogenous treatment with hCG; however, the animals showed premature menstruation, in spite of high progesterone levels (above 4 ng/ml). Treatment around the time of implantation (between Days 8 and 12 after the mid-cycle peak in estradiol levels) in mated animals provided 100% pregnancy protection. Treatment of pregnant animals on Days 30-32 of the menstrual cycle, i.e. about Day 20 after the estradiol peak, induced abortion in 8 of 10 animals. A significant (p less than 0.05) decrease in serum progesterone levels was observed on Day 3 after the initiation of treatment. However, the decrease was slower (slope: -0.36, r: 0.96) compared to that observed in nonpregnant animals (slope: -0.72, r: 0.95). In the other two animals, pregnancy was not affected. However, when the treatment was delayed until about Day 50 after the estradiol peak, all four animals aborted. This study suggests that lilopristone is a progesterone antagonist with a potential to induce menstruation, inhibit nidation, and terminate pregnancy. The antifertility effects are mediated through blocking progesterone action at the endometrium as well as decreasing progesterone bioavailability, which appears to be due to its effects on gonadotropin release.

Animals↗

Effects of pre-ovulatory X-irradiation on fertilization, initial cleavage and post-nidation development in the Chinese hamster.

In order to investigate the effects of pre-ovulation X-ray radiation on fertilization, initial cleavage and post-nidation development, Chinese hamster dams were mated with normal males after exposure to 200 rads of radiation during the primary maturation period, and cytogenetic studies were performed at 2.5, 3.5 and 10 days after fertilization; comparison studies were also performed on an untreated control group. The results indicated that: (1) The ovarian ova with chromosomal anomalies induced by X-ray radiation had the ability to be fertilized and transmit the abnormality to the 2-celled stage, but most of them deceased by the 8-celled stage. (2) The embryos attaining the 8-celled stage with normal chromosomes were implanted and survived, but showed remarkable hypoplasia on day 10 of gestation.

Animals↗

Uterine blood flow, pH, and pCO2 during nidation in the guinea pig: ovarian regulation.

The regulation of uterine blood flow (UBF), intrauterine pH (IUpH), and carbon dioxide levels (IUpCO2) by ovarian steroids during the nidatory period was examined in the guinea pig to determine if changes in the intrauterine environment are associated with cyclic changes in ovarian function. Between days 4 and 8 (day 0 = ovulation) of pregnancy, guinea pigs were prepared for the simultaneous in situ measurement of UBF, IUpH, and IUpCO2, and the changes in these parameters were compared to serum levels of 17 beta-estradiol (E2) and progesterone (P). The same parameters were evaluated in ovariectomized guinea pigs treated with oil, 1 or 10 micrograms E2, 2 mg P, or 1 microgram E2 plus 2 mg P (P2E1). UBF rose between days 4 and 5 to peak at the expected time of nidation on day 6 before declining to basal levels by day 8. Similar fluctuations were observed in IUpCO2 and serum E2 levels, while IUpH fluctuated in a manner opposite to that of IUpCO2 levels. Serum P levels remained constant between days 4 and 8. Both P and E2 treatments elevated IUpH but depressed IUpCo2, compared with levels in ovariectomized oil-treated controls. An elevation in UBF rates was also observed in E2-treated animals. Combined P2E1 treatment elevated UBF and IUpCO2 above oil-treated control levels and lowered IUpH. These data indicate that a causal relationship exists among UBF, IUpCO2, and serum E2 fluctuations during the nidatory period in the guinea pig and that these parameters are inversely related to changes in IUpH. It is suggested that ovarian regulation of the intrauterine environment may have a direct effect on the timing of blastocyst implantation in the guinea pig.

Animals↗

Relation between daylight ratio, plasma progesterone levels and timing of nidation in mink (Mustela vison).

Mink were mated between 17 February and 22 March. In females kept in natural daylight concentrations of progesterone, measured by radioimmunoassay, began to rise between 25 and 30 March, whatever the date of mating. After reaching peak values of 40--160 ng/ml, progesterone concentrations decreased before the end of pregnancy. In females given 14 h light/24 h immediately after mating, the rise of progesterone began a few days earlier, indicating that the extra light induces earlier progesterone secretion, nidation and parturition.

Animals↗

[Effects of low doses of lynestrenol on endometrium and nidation (author's transl)].

In 10 women taking 0.5 mg lynestrenol for oral contraception endometrium biopsies were carried out in several consecutive cycles between the 21st and 25th day of each cycle. In addition pregnandiol excretion in the urine was measured in one of the last three treatment cycles always on the 10th and 21st day of cycle. During treatment of a characteristic, monomorphic microscopical endometrium picture was observed with hardly distinct endometrium glands and only slight decidualike transformation of cellular elements of the stroma. From these histological pictures it is concluded that oral application of 0,5 mg lynestrenol produces endometrium changes characterized by insufficient transformation so that nidation of a blastocyte becomes impossible.

Biopsy↗

Tissue engineering: in vitro embryonal nidation in a murine endometrial construct.

The epithelial and mesothelial cellular components of organs can be obtained as dissociated cells using adequate procedures of enzymatic digestion followed by pycnotic separation on density gradients. Using a specially developed procedure for tissue dissociation, the epithelial and connective tissue components of endometria from pseudopregnant mice were grown in culture using a combination of three dimensional culture of connective tissue components in collagen gel, with the superimposition of epithelial components in liquid medium on the surface of the gells. After a few days of growth, when the cultures became dense, murine blastocysts obtained on postcoital day 4.5 by fallopian flushing of hormonally primed and mated mice, were transferred onto the imitated endometria. The blastocysts hatched and grew on the endometrial epithelium as spherical coherent conglomerates of cells quite different from hatched blastocysts grown on the surface of a petri dish, in which the presumtive trophoblasts spred around the central mass. Light and electronmicroscopy of resin embeded sections (2 days after nidation on the simulated endometria) revealed that at least two populations of cell types were recognisable as layers. This is interpreted as an early sign of morphogenesis and the first visible steps of differentiation. The presence of mitotic figures indicates viability and continuing growth. Electronmicroscopy of cell types grown under conditions simulating in vivo tissue architectonics showed overtly less cytopathology and better cell function. Simulated endometria may, therefore, serve as an attractive model for studying early mammalian embryogenesis and the effects of toxic agents.

Animals↗

Biology of nidation and ectopic implantation.

The incidence of ectopic pregnancy has been steadily growing during the past decade; this fact can only partially be related to known factors (PID, use of IUDs, minipill, inductors of ovulation, sterilization reversal). Ectopic pregnancy is still a frequently misdiagnosed pathology; nevertheless, the recent advances in early diagnosis have allowed a decrease in the mortality rate and an improvement in subsequent fertility. In absence of obvious tubal abnormalities it is difficult to assess the cause of an ectopic implantation. Yet the factors regulating and nidation of the embryo in the human are far from clear. The transport of the embryo in the oviductal fluid depends on ciliary beat (generally regarded as the leading factor) and on muscle contractions mainly in the ampullary-isthmic and in the utero-tubal junction, where a sphincter action is stimulated by estrogens and relaxed by progesterone. Other substances (catecholamines, prostaglandins, oxytocin) are thought to be involved in ovum transport, although their role is unclear. Even less is known about local influence of the embryo on the oviduct. During preimplantation and implantation both the embryo and the mother engage in an elaborate interaction, elsewhere referred to as a 'conversation', involving long-and short-range signals. An essential role is played by the endocrine luminal milieu. A local action of estrogens on a progesterone-primed endometrium may be required for either the release of crucial signals for the blastocyst activation, or to make epithelial cells sensitive to the presence of the embryo, thus inducing the decidualization. In some animals, these estrogens are not ovarian, but synthesized by the blastocyst itself.(ABSTRACT TRUNCATED AT 250 WORDS)

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