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Biomedical subjects

H M Beier

Publications and source records attributed to H M Beier.

At least 91 records · Page 5Linked to original sources

The effect of clomiphene citrate on blastocyst development and implantation in the rabbit.

The induction of ovulation with clomiphene citrate (CC) in human patients results in a high ovulation rate but achieves a relatively low pregnancy rate. To clarify the possible role of CC in interfering with the normal reproductive physiology and embryology, we have used our rabbit model and transferred 4-day-old blastocysts from untreated donors to CC-treated pseudopregnant recipients and from CC-treated donors to untreated pseudopregnant recipients to study embryonic development and implantation. Each group was further subdivided into two subgroups, one receiving CC before and the other after ovulation. CC was administered subcutaneously in three consecutive doses of 10 mg/kg body weight. Ovulation was induced with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG). The implantation rate of the control group, evaluated on day 8 of pregnancy, reached 62.0%. When recipients were treated with CC before ovulation, implantation rate was reduced to 18.8% (P less than 0.0002), and to 20.0% (P less than 0.003) when CC was administered after ovulation. The implantation rate of blastocysts transferred from donors, treated before ovulation, is 22.2% (P less than 0.0055), however, reached 70.8% when treatment was started after ovulation. All implantations were analysed microscopically and showed normal morphological features. Our results demonstrate a potential multiple effect of CC, first on the endometrium by altering its receptivity for the implanting conceptus, second, on tubal physiology by altering egg transport, and finally on ovum maturation before ovulation interfering with development of blastocysts. These parameters may all result in rapid decrease in establishment of implantations and in turn in very low pregnancy rates.

Animals↗

Effect of clomiphene citrate on the rabbit ovary.

The effect of clomiphene citrate on the rabbit ovary was studied in mature nulliparous rabbits pretreated with three consecutive doses ranging from 0.01-10.0 mg/kg per day. With increasing doses a trend of decrease in mean ovarian weight (mg/kg body weight) is observed 2 days after termination of treatment. Five days later a significant increase occurs, which then subsides again to control values on day 12 after termination of treatment. During this period, no matings or injections of luteinizing hormone were performed to trigger ovulation; consequently no ovulations are observed. Folliculogenesis appears as normally; number and morphology of follicles are within normal ranges. No endogenous, spontaneous gonadotropin surges are detected in blood serum up to the 7th day after termination of treatment (2 and 10 mg doses). The surface epithelium of the ovary resembles normal germinal epithelium; however, after treatment with high doses a "secretory"-like activity is observed, accompanied with ultrastructural changes.

Animals↗

Immunocytochemical localization of uteroglobin in the rabbit endometrium.

Uteroglobin, the progesterone dependent pregnancy-characteristic endometrial protein in the rabbit, is found within the endometrial epithelium on the fourth and sixth day of pregnancy at the electron-microscopic level by use of the immunoperoxidase technique and a specific anti-uteroglobin serum from the sheep. As known from earlier studies, uteroglobin is the predominant protein synthesized of the endometrial secretion. In the present study, it is localized exclusively in the non-ciliated epithelial cells. A common route of secretory proteins within these cells is observed by uteroglobin labelling: rough endoplasmatic reticulum----Golgi complex----condensing vesicles----secretory products. Uteroglobin occurs in small vesicles on the trans-face of the Golgi complex, and in addition beneath the apical plasma membrane where it appears in membrane-bound vesicles, which apparently are extruded into the uterine lumen. Most of the uteroglobin is located in the luminal secretion. The distribution of intracellular uteroglobin is found only in cells of the basal endometrial gland, adjacent to the myometrium. The cytoplasm of uterine epithelial cells facing the cavum does not show uteroglobin reaction products.

Animals↗

Oxidative and conjugative metabolism of diethylstilbestrol by rabbit preimplantation embryos.

Five- and six-day-old rabbit preimplantation embryos were found to be capable of metabolizing [3H]diethylstilbestrol (DES) in vitro. Based on the analysis of the metabolites formed during a 24-hr incubation period we conclude that these early stage embryos do have active monooxygenase and conjugative activity. The monooxygenase seems to be specific to this early stage of embryonic development.

Animals↗

Effect of clomiphene on the functional morphology of oviductal and uterine mucosa.

The effect of clomiphene on the functional morphology of the uterine and oviductal mucosa was studied in rabbits by means of light and electron microscopy (SEM and TEM). Tissues were obtained from mature nulliparous animals receiving subcutaneous doses ranging from 0.01-10 mg/kg per day. In all cases the effects were evaluated 2 days after termination of treatment. With 2 and 10 mg, effects were studied up to 12 and 7 days, respectively. Normally appearing oviductal and endometrial tissues, corresponding to various stages of the cycle, were observed with doses up to 5 mg. However, a burst of cellular secretory activity becomes evident with the administration of higher doses. Apical protrusions or cytoplasmic portions seem to be extruded, and draw attention. These cytologic events are concentrated near gland openings in the endometrium and can be seen abundantly among cilia of oviductal cells. Other ultrastructural changes are evident as well. These histologic changes may reflect nonsynchronous cellular activities which in turn interfere with oviductal and endometrial functions before implantation.

Animals↗

Immunocytochemical localization of uteroglobin in the genital tract of male rabbits.

Using the immunoperoxidase technique and specific goat anti-serum to uteroglobin, selective immunochemical staining products are localized in the epididymal epithelium of the caput and proximal corpus region, at the adluminal border of the cauda epididymidis and, as well known, in epithelial cells of the endometrium of pregnant and progesterone-treated rabbits. Specific staining is also seen on spermatozoa. A uteroglobin-like antigen has been similarly localized in alveolar and bronchial epithelial cells of the lung. Testis, prostate, seminal vesicle and ductus deferens do not seem to contain in their tissues immunoreactive uteroglobin-like antigens. Similarly, the uterus and ductus epididymidis of immature rabbits are devoid of immunoreactivity. The presence of uteroglobin-like antigens in tissues other than the endometrium, particularly the ductus epididymidis, stimulates new discussions on the function of this protein in reproductive physiology and fertility research.

Animals↗

Effects on fertilization of rabbits of insemination with ejaculates treated with PG-dehydrogenase and antisera to PGE-2 and PGF-2 alpha.

PGE-2 and PGF-2 alpha in rabbit semen were selectively inactivated by incubation with antisera, or most of the seminal prostaglandins were transformed into biologically inactive 15-keto-prostaglandins by prostaglandin-15-hydroxydehydrogenase(PG-15-HDH). These treated ejaculates were vaginally inseminated. Compared to the controls (738 eggs of which 94% were fertilized) a dose-dependent reduction of the fertilization rate was observed with the anti-PGF-2 alpha-treated ejaculates. A non-uniformly, but statistically significantly reduced fertility was found in the other 2 treatment groups. After incubation with higher doses of PG-15-HDH, some fertilization was accomplished with ejaculates showing an extremely weak forward progression or immotile spermatozoa. An improvement in sperm motility, however, was observed in ejaculates treated with antiserum to PGF-2 alpha. Seminal prostaglandins may not exclusively affect sperm motility. The observed influences on the fertilization rate after treatment of spermatozoa with antisera to PGE-2 and PGF-2 alpha or PG-15-HDH suggest that these are local effects in the female genital tract.

Animals↗

Cytosol and nuclear progesterone-receptor concentrations in the rabbit endometrium during early pseudopregnancy under different treatments with estradiol and progesterone.

In an attempt to understand the mechanism of the antiprogestational action of estrogens during early pseudopregnancy we determined the cytosolic and nuclear concentrations of progesterone receptors in the endometrium of rabbits treated with hCG followed by various combinations of estradiol and progesterone. The progestational response of the endometrium was followed by quantitation of the uteroglobin content in the uterine lumen. In rabbits treated with hCG alone there was a clear progestational response (40% relative uteroglobin content), but only 16% of the progesterone receptors were located in the nucleus. After additional treatment with progesterone the progestational response remained high (45% relative uteroglobin content), the total cellular content of progesterone receptor increased, and 5% of the complexes were found in the nucleus. These findings suggest that a consumption of nuclear progesterone receptor is required for progestational action. Treatment of pseudopregnant rabbits with estradiol resulted in a marked increase not only of the total cellular progesterone receptor but also of the percentage of it located in the nucleus (35%). Concomitantly, the progestational response was markedly inhibited (5% relative uteroglobin content). These results confirm the relevance of nuclear consumption of progesterone receptor for progestational action, and suggest that some antiprogestational effects of estrogens may be due to their interference with the mechanism of progesterone receptor processing.

Animals↗

[Anatomy of cervical changes at the end of pregnancy (author's transl)].

The problem of anatomical changes in the uterine cervix at the end of pregnancy is discussed and contrasted to the anatomy of the uterine corpus during pregnancy. The muscles of the uterine cervix have proven functionally unimportant in contrast to earlier held views. However, the function of the myometrium of the uterine corpus has its well known significance. Very important changes appear, on the other hand, in the connective tissue of the cervix. The collagen and the ground substance are metabolized completely. As a consequence, the resulting structural transformation allows rapid dilatation of the cervix during delivery. We have to admit that, unfortunately, we have no causal explanation for the overal control of this connective tissue transformation either by hormones or by the autonomic nervous system.

Autonomic Nervous System↗

Uteroglobin-like antigen in the pulmonary epithelium and secretion of the lung.

The immunological identity of a uteroglobin-like protein, occurring in respiratory tract secretions and tissue, with uteroglobin from rabbit endometrial secretion is demonstrated. A uteroglobin-like antigen has been localized in bronchial epithelial cells and in bronchioles by immunofluorescence. This secretory protein is, in contrast to the authentic uteroglobin, hormone-independent, as far as estrogens and progesterone are concerned. The possible significance of comparative studies on uteroglobin and the uteroglobin-like antigen is discussed, taking into account cytological, endocrinological, and molecularbiological aspects.

Animals↗

Significance of maternal uterine proteins in the establishment of pregnancy.

Mammalian embryonic development depends on extrinsic support by the maternal organism. During the preimplantation period the growing blastocyst needs favourable environmental conditions, which are provided by endometrial transformations and secretion. The macromolecular composition of uterine secretion at different times before implantation is characterized by a spectrum of protein patterns which change daily. In an attempt to shed light on the significance of the uterine secretion proteins, particularly uteroglobin in the rabbit, in the establishment of early pregnancy, analyses are reported which demonstrate the origin and endocrine control of the synthesis and release of these proteins. In a comparative study of blastocyst development in vivo and in vitro the significance and consequences of asynchrony between the embryonic and maternal reproductive phases are investigated. Particular attention is drawn to uterine influences on the rabbit blastocyst coverings, and how embryonic development can be retarded by abnormal structural transformation of the zona pellucida and the mucin coat. Finally, the covenient experimental systems of pseudopregnancy and of delayed uterine secretion in the rabbit permit an approach the question of whether the uterine macromolecular components constitute a maternal response to the presence of the as yet unimplanted blastocyst.

Animals↗

Characteristics of the purified uteroglobin-like protein from rabbit lung.

A uteroglobin-like protein was prepared from lung extracts of female rabbits by absorption to immobilized anti-uteroglobin immunoglobulin and purified to homogeneity by gel filtration on Sephacryl S-200. The final preparation is indistinguishable from uteroglobin according to its behaviour in Ouchterlony double-diffusion, polyacrylamide gel electrophoresis under denaturing and non-denaturing conditions, ultraviolet spectrum, tryptic peptide analysis, and progesterone-binding properties. Progesterone binding to the lung protein exhibits an affinity similar to that observed with authentic uteroglobin and is equally enhanced by reduction of the protein with dithiothreitol. Competition experiments with non-radioactive steroids demonstrate a similar steroid-specificity for both proteins. Progesterone binding causes a perturbation in the ultraviolet absorbance of tyrosine residues of the lung protein similar to that observed with uteroglobin. These data suggest that the proteins prepared from both sources are biochemically identical.

Animals↗

Studies on the innervation of the endometrium.

The innervation of the endometrium of rabbit, rat, mink, mongoose and pig has been investigated electron microscopically. Large bundles of nerve fibers can be observed in the connective tissue spaces within the basal layer of the endometrium. Unmyelinated nerve fibers enter the lamina functionalis, terminal nerve fibers penetrate the basal lamina and make contact with the glandular and the cavum epithelial cells. The terminal axons contain abundant synaptic vesicles, dense core vesicles and mitochondria. To date, no specialized presynaptic or postsynaptic membranes have been found.

Animals↗