Nucleolar Channel System Research Articles

Interfering with implantation by postcoital estrogen administration II. Endometrium epithelial cell ultrastructure

Secretory human endometrium was studied by electron microscopy after high-dose ethinylestradiol administration, a method used for interception (morning-after pill). Medicated (experimental) cycles were compared to non-medicated (control) cycles in the same volunteers. The nucleolar channel system typically present in the nucleus of the epithelial cell in secretory phase of the human endometrium disappears completely as a result of this treatment, resulting in a nucleolar basket structure. Glycogen deposits were prominent at the basal membrane and in the apex of the cell during the experimental cycle. Giant mitochondria were observed to occur to similar extent during control and treatment cycles. This study confirms the morphological delay found in light microscopic studies, published earlier with diethylstilbestrol and with ethinylestradiol.

Endometrial morphology in stimulated in vitro fertilization cycles and after steroid replacement therapy in cases of primary ovarian failure

Endometrial morphology and ultrastructure are studied in 17 spontaneous, 23 stimulated, and 18 artificial cycles in cases of primary ovarian failure. Normal light-microscopic aspect was found, but impaired development of nucleolar channel system and stronger intercellular junction have been observed by electron-microscopic studies in stimulated cycles with relative excess of luteal estrogen. Normal glandular maturation can be obtained in patients with premature menopause, given adequate steroid replacement, but an abnormally dense fibrocytic aspect of the stroma is characteristic of the first treatment cycles.

Nucleolar channel system in the human fetal endometrium

Endometrial tissue from 3 human fetuses was examined electron microscopically. In 2 of the fetuses the nucleolar channel system was found within the nuclei of the endometrial epithelium. This finding demonstrates that the development of the system is not dependent on ovulation. We speculate that an appropriate concentration ratio between estrogen and progesterone might induce the development of nucleolar differentiation.

Ultrastructural changes in human endometrium at different phases of the menstrual cycle and their functional significance.

A review of the ultrastructure of normal human endometrium at different phases of the cycle is presented. The structural changes are correlated to the functional implications in the light of the recent knowledge on the functioning of cell organelles. Relatively undifferentiated cells of the beginning of the menstrual phase become functionally matured, proliferate and later degenerate. The appearance of the nucleolar channel system during the secretory phase coincides with the rise of progesterone level and facilitates the nucleocytoplasmic exchange. The secretion of the endometrial glands consists of glycogen, glycoproteins, lipids and mucopolysaccharides. Large autophagic vacuoles (giant lysosomes) digest various cell components at the end of the cycle. All the lamina functionalis of the endometrium is not shed, a part of it is regressed by focal death (autophagic vacuoles) and by total death (apoptosis) of individual cells.

In vivo production of the nucleolar channel system in post menopausal endometrium.

Endometrial biopsies from seven postmenopausal women on hormone replacement therapy have been examined for the presence of the unique nuclear structure, the nucleolar channel system. Its identification in five of the patients has demonstrated that the nucleolar channel system can be produced by an appropriate oestrogen and progestagen treatment and is not otherwise dependent on ovulation.

Action of a midcycle contraceptive (R 2323) on the human endometrium

Over 2,148 cycles of midcycle oral administration of R 2323 (50 mg. per day on Days 15, 16, and 17), the authors recorded a drug-failure pregnancy rate of 5 per cent and an unusually regular cycle length of 28 ± 2 days. During this trial, endometrial biopsies obtained in the luteal phase were examined by light and electron microscopy and compared to pretreatment biopsies. Light microscopy indicated a weakly secretory endometrium suggestive of some, albeit low, progesterone impregnation. Ultrastructural examination revealed deleterious changes in the development of the nucleolar channel system and giant mitochondria and a delay in the migration of glycogen granules. This low progesterone impregnation could be explained either by a direct effect of R 2323 on cell ultrastructure or by interference with progesterone availability. It would appear that R 2323 acts as a temporary substitute for progesterone at the receptor level but that it does not induce all the biological manifestations of this hormone, in particular, the endometrial changes required for implantation.

The morphogenesis and fate of the nucleolar channel system in the human endometrial glandular cell

Endometrial curettings from 32 healthy women at all stages of the menstrual cycle were surveyed for the occurrence of nucleolar channel systems. Typical nucleolar specializations were noted in 8 of the 20 women biopsied between day 13 and day 26 of the menstrual cycle and were observed most commonly and in greatest numbers between day 17 and day 20. The nucleolar channel system develops at the apex of an invagination of both inner and outer nuclear membranes. It is an ordered, hollow, spherical stack of interdigitating membrane-bound tubules of 60–100 nm diameter embedded in a dense granular matrix surrounding a core of lightly granular material. A three-dimensional reconstruction of the structure is presented. Toward the end of the cycle the nucleolar channel system appears more commonly as a dense, disordered mass of tubules lacking a central core, often occurring as a protrusion of the nucleus. Micrographs suggesting extrusion of the channel system and possible incorporation into giant lysosomes are presented. The functional relationships of the nucleolar channel system are discussed, and the suggested architectural arrangement of the system is correlated with the molecular biology of the endometrial glandular cell.

Ultrastructure of human uterine epithelium at the time of implantation after postovulatory administration of norethindrone.

The present investigation was performed to elucidate the mechanism of action of the previously demonstrated contraceptive effect in women of postovulatory administration of a synthetic gestagen, norethindrone (NET). Seven women participated during 3 control cycles and during 8 treatment cycles, in which NET was given orally after ovulation. Daily peripheral plasma levels of progesterone, estradiol and NET were assayed. An endometrial biopsy was taken in all cycles at about the expected time of implantation. Light microscopy revealed no consistent differences between non-treatment and treatment cycles but electron microscopy indicated that, after NET treatment, the mitochondria had grown larger and that nucleolar channel system had appeared. These changes suggest an increased progesterone-like influence upon the epithelium, despite the decreased progesterone plasma levels, caused by NET. It is assumed that these structural changes, caused by the postovulatory NET treatment, might change the functional properties of the endometrium and thereby impair the possibilities for normal implantation.

Mechanisms involved in progesterone contraception and estrogen interception

While there are certain differences between biological responses to C-21 progestogens and the 19-norsteroids, precoital progestogens in general interfere with sperm transport, fertilization, and ovum transport. A 36 hour interval was required to achieve 100 per cent precoital contraceptive effectiveness in the rabbit. At marginal doses or timing, blastocyst degeneration may occur, and with large doses of progesterone at the time of coitus some teratogenic effects were noted. Postcoital estrogen is associated with lowering of plasma progesterone levels. Concomitant progesterone administartion, however, does not completely reverse the interceptive effect of estrogen. Direct effects on the endometrium include disintegration of the nucleolar channel system, retention of glycogen in endometrial glands, decreased alkaline phosphatase, and lowered endometrial carbonic anhydrase. The latter may be the basic mechanism of action.

EFFECT OF POSTOVULATORY OESTROGENS ON THE FINE STRUCTURE OF THE EPITHELIAL CELL IN HUMAN ENDOMETRIUM

Treatment of secretory human endometrium with oestrogens, both in vivo and in vitro, results in a disruption of the nucleolar channel system, an organelle typically found in the epithelial cell of normal human endometrium during the postovulatory phase. The most striking effect is the loss of dense particles in immediate proximity to the channels, and the disappearance of particulate masses normally found in the nucleoplasm surrounding the channel system. Other fine structural elements, such as giant mitochondria and glycogen, are unaffected except that less glycogen migrates to the apex of the cells.

Progesterone-specific protein crystals in the endometrium: An electron microscopic study

Electron microscopic examination of endometrium from castrated women and rabbits given progesterone reveals cytoplasmic crystalloid structures. The appearance of these crystalloids in human endometrium is concomitant with the formation of a nucleolar channel system. Estrogen administration without progesterone does not induce these changes.

In vitro Production of Nucleolar Channel System by Progesterone in Human Endometrium

ELECTRON microscope examination of normal human endometrium during the midsecretory phase of the menstrual cycle demonstrates that the nucleolus of the epithelial cell differentiates into an organelle variously termed a nucleolar canalicular system1, a nucleolar basket2 or a nucleolar channel system3. Such a structure appears if ovulation has occurred. Nucleolar baskets have been seen as early as the sixteenth day of a normal 28 day cycle. After this they may increase in number, reaching a maximum around the twentieth day and then disappear, not being found later in the cycle. They have not been seen in the proliferative phase of the cycle or in early pregnancy.

Intranuclear tubules in trophoblast III of rat and mouse chorioallantoic placenta

A system of tubules in trophoblast III nuclei of rat and mouse choriollantoic placenta is described. The intranuclear tubules are arranged in compact tubular units. Individual tubules measure 600–3500 A in diameter and are not delimited from the nucleoplasm by nuclear envelope. Trilaminar tubular membranes are continous with the inner nuclear membrane and the endoplasmic reticulum is continous with the outer nuclear membrane. A system of confluent spaces that extend from the intratubular space through the perinuclear space into the cisternae of the rough endoplasmic reticulum is demonstrated. Similarities of this system to the “nucleolar channel system” of human endometrium are discussed.

Fine Structural Effects of Intrauterine Contraceptives on the Human Endometrium

Of 198 endometrial biopsies performed on 82 women with Lippes loops in situ for 6 weeks to 40 months 124 were proliferative and 74 were secretory. Samples were obtained from immediately beneath the device between the loops and from areas remote from the device. Specimens of basal endometrium lower segment or endocervix were excluded. Control tissue was obtained before insertion of the device. Slides were prepared for electron microscopy. No consistent generalized pathologic change was observed in either proliferative or secretory endometria. The stroma immediately beneath the loop appeared compressed and fibrotic throughout the cycle. Proliferative epithelium maintained the normal pattern of juxtaposed light and dark (electron-dense) cells mitotic activity and distribution of microvilli and cilia. No progression of epithelial ultrastructural differences occurrred after their first appearance in the second month after IUD insertion. Precocious changes in epithelial ultrastructure included 1) the appearance of a nucleolar channel system normally considered indicative of ovulation or exogenously administered hormones in 15-29% of endometria judged to be preovulatory; 2) numerous large mitochondria usually associated with the postovulatory phase in the late-proliferative endometrium and occasionally as early as in the midproliferative; and 3) the development of confluent fields of glycogen at the end of the proliferative phase a few days earlier than in controls. The premenstrual endometrium resembled the contrl of this stage; scarcity of microvilli and other characteristic ultrastructural traits of regression were noted. Ultrastructural changes in the proliferative stroma were observed first about 1 day preovulatory when the cytoplasm appeared better differentiated than in the controls. The stromal cells were highly differentiated at the end of the first postovulatory week; the cytoplasmic complexity at Days 19 or 20 often resembled that of Day 25 controls. Premature and asynchronous development of the endometrium may affect the correlation with ovular development which is a prerequisite for normal implantation. Since the IUD creates an unfavorable environment for blastocystic attachment but does not dislodge the implanted ovum its action is considered contraceptive rather than abortifacient in the usual sense.

INTRAUTERINE DEVICES

The human endometrium, studied with the electron microscope, undergoes asynchronous and premature cyclic development in response to inin uterine contraceptive devices. Typical nucleolar channel systems and other cellular characteristics of the normal secretory phase appear before ovulation, and decidualization occurs several days prematurely. Disturbance of the synchrony of ovular and endometrial development may be a mechanism of contraceptive action of these devices.

Intrauterine devices: effects on ultrastructure of human endometrium.

The human endometrium, studied with the electron microscope, undergoes asynchronous and premature cyclic development in response to inin uterine contraceptive devices. Typical nucleolar channel systems and other cellular characteristics of the normal secretory phase appear before ovulation, and decidualization occurs several days prematurely. Disturbance of the synchrony of ovular and endometrial development may be a mechanism of contraceptive action of these devices.

The nucleolar channel system of human endometrium.

Human endometrium taken during the early to mid-secretory portion of the menstrual cycle is studied with the electron microscope. A description of the nucleolus is given. In addition, an unusual structure within the endometrial cell nucleolus is described, consisting of amorphous matrix, 150-A dense granules, and a series of tubular channels. This structure is named the nucleolar channel system. A description is given of the geometric variability of the nucleolar channel system, its contents, and its relationship to the cytoplasm. The morphologic basis for a nucleolar-cytoplasmic interrelationship via the nucleolar channel system is described. Some of the implications of this relationship are discussed. The work of previous investigators on the nucleolar channel system is discussed.