Epithelium Of Uterus Research Articles

Expression of Interferon Epsilon in Mucosal Epithelium is Regulated by Elf3.

Interferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors. We demonstrate here that Ifnε is regulated by Elf3, an epithelial restricted member of the ETS family. It is co-expressed with IFNε at the epithelium of uterus, lung and intestine, and we focused on regulation of IFNε expression in the uterus. Promoter reporter studies demonstrated that Elf3 was a strong driver of Ifnε expression; knockdown of Elf3 reduced expression levels of IFNε; Elf3 regulated Ifnε expression and chromatin immunoprecipitation (ChIP) confirmed the direct binding of Elf3 to the IFNε promoter. These data show that Elf3 is important in regulating protective mucosal immunity by driving constitutive expression of IFNε to protect mucosal tissues from infection in at least three organ systems.

The effects of metformin treatment on the ovaries and uterus of offspring

Objective The aim of this study is to investigate the effects of metformin treatment at different dosage levels on the ovaries and uteruses of rat offspring in the course of the intrauterine period. Methods Saline, metformin (100 mg/kg/day), and metformin (200 mg/kg/day) were administered via oral gavage between the 6th and 15th days of gestation to the 9 pregnant rats (n = 3/group). After birth, 5 female offspring were separated from each group and perfused on the 60th day of postnatal development. The cortex and medulla volumes of the ovaries, the thicknesses of epithelium and endometrium of the uteruses and the total oocyte number density were estimated. In addition, the estradiol levels in blood samples were measured by the ELISA method. Results There were no statistically significant differences among the groups regarding the number of oocytes, the volumes of ovarian cortex, medulla, primary and secondary follicles (p > .05). In comparison with the control group, the volume of the tertiary follicle, the thickness of the uterus epithelium, and the estradiol level were significantly decreased in Metformin 200 group (p < .05). Conclusions The gestational exposure to high dose metformin may result in decreased estradiol production and subsequently decreased endometrial thickness of offspring rats.

Expression patterns of TLR4 mRNA and protein in the equine endometrium during early pregnancy

Toll-like receptors (TLRs) are an important part of the innate immune system and play a role in activating the acquired immune system. TLR4 is the best characterised of the many TLRs; its signalling mechanisms are known to be mediated by many inflammatory pathways and by endogenous substances. The aim of the present study was to elucidate the expression profiles for TLR4 mRNA and protein and determine the cell-specific localisation of TLR4 in the equine endometrium during the oestrous cycle and early pregnancy. Endometrial biopsy samples were obtained from mares during early pregnancy (on day 14, P14, n = 4) and, for comparison, on day 14 of the oestrous cycle (late dioestrus, LD, n = 4) and when luteolysis was completed (after luteolysis, AL, n = 4). Total RNA was extracted and transcribed into cDNA, and the relative expression of TLR4 mRNA was quantified by qPCR. Immunohistochemistry was used to define the spatio-temporal localisation of TLR4 protein in the uterus. Expression of TLR4 mRNA was reduced (P &amp;lt; 0.05) on P14 compared to LD. The expression of TLR4 mRNA was similar for P14 and AL. TLR4 protein was localised mainly in the luminal and glandular epithelia, but was also present in endothelial cells of capillaries. Compared to P14, TLR4 protein was abundant in both luminal and glandular epithelia of uteri of mares in LD. These results suggest that downregulation of TLR4 in the endometrial epithelia in early pregnancy may play a role in the immune tolerance mechanisms that protect the conceptus (embryo/foetus and associated membranes).

Expression and localization of transient receptor potential channels in the bovine uterus epithelium throughout the estrous cycle.

Transient receptor potential (TRP) channels are expressed in the endometrium but it is unknown if they are modulated through the estrous cycle (EC). This study was undertaken to identify the modulation of the TRPC gene and protein isoforms in bovine uterine epithelium, as a model for human, throughout the EC. Changes in the expression of TRPC genes in bovine uterine epithelium throughout the EC were measured using Real-Time PCR, while immunohistochemistry and immunocytochemistry were used to determine the localization of these channels. Out of the 7 members of the TRPC family, TRPC1, 2, 3, 4 and 6 genes were expressed in bovine uterine epithelial tissue and TRPC 5 and 7 were not. Gene expression levels of all TRPC isoforms underwent cyclical changes throughout the EC. Moreover, cyclical changes were detected in the protein levels of TRPC1 and TRPC6 throughout the EC. These findings show that TRPC channels are modulated through the EC and therefore may have a role in reproductive events.

Medical Images Classification and Diagnostics Using Fuzzy Neural Networks

The problem of medical images of cervix epithelium classification for express diagnostics is considered…The following states of cervix epithelium are to be recognized and classified: normal state - columnar epithelium; squamous epithelium (normal state); metaplasia-benign changes of cervix uterus epithelium; CIN1-displasia of light degree, CIN 2-displasia of middle degree, CIN 3-displasia of high degree- intra-epithelium cancer: For its solution the application of fuzzy neural network (FNN NEFClass M) is suggested. The application of FNN is grounded by its following properties: it may work with fuzzy and qualitative information; it has accelerated convergence as compared with crisp classification methods; it enables to attain better classification accuracy than conventional classifiers. The structure of FNN NEFClass and its model description are presented. Training algorithm stochastic gradient descent for membership functions of fuzzy sets is considered and implemented. Data set of medical images of cervix epithelium which was obtained by special device colposcope is described and some images are presented. The experimental investigations of FNN NEFClass application for medical images recognition on real data are carried out, the results are presented. The comparison with NN Back Propagation, RBF NN and cascade RBF NN was made and estimation of efficiency of the suggested approach was performed. The problem of reduction of features number in classification tasks using principal component method (PCM) method is considered and implemented.

Comparative Anatomical Studies on the Uterus of Pati and Chara-Chemballi Ducks during their Laying Periods

In the present investigation, twelve eachPati and Chara-Chemballi ducks were utilized at 42 weeks of age. The uterus was collected immediately after death and studies were made on it. The uterus was a sac-like dilation between the isthmus cranially and the vagina caudally and was located just ventral to the synsacrum. The length, breadth, thickness and weight of uterus of Chara-Chemballi ducks were significantly higher than Pati duck. The mucosa of uterus of both Pati and Chara-Chemballi duck showed many leaf shaped folds. These folds were mainly primary, secondary and tertiary types. In some primary folds concave surface were also present. The surface epithelium of uterus was pseudostratified ciliated columnar in both Pati and Chara-Chemballi ducks. The mean height of lamina epithelialismucosae of uterus was 28.058±0.367μm in Patiduck and 33.228±0.234 μm in Chara-Chemballi duck. The surface epithelium and glandular epithelium showed moderate PAS positive reaction in both Pati and Chara-Chemballi ducks. Histologically, there is no significant difference between the Patiand Chara-Chemballi ducks. However, the height of lamina epithelialis mucosae of oviduct was significantly higher in Chara-Chemballi duck than Pati duck.

The estrogenic effects of apigenin, phloretin and myricetin based on uterotrophic assay in immature Wistar albino rats

Chemicals that occur in vegetal food and known as phytoestrogens, because of their structures similarity to estrogen, have benefits on chronic diseases. Despite this, when they are taken at high amounts, they can cause harmful effects on endocrine system of human and animals. In this study, it has been intended to determine the estrogenic potencies of phytoestrogens apigenin, phloretin and myricetin whose affinities for estrogen receptors in vitro. The female rats divided into 17 groups, each containing six rats. There was a negative control group and there were positive control dose groups which contains ethinyl estradiol, ethinyl estradiol+tamoxifen and genistein. The other dose groups which were tested for estrogenic activity contains apigenin, myricetin and phloretin All chemicals have been given to Wistar immature female rats with oral gavage for 3 consecutive days. By using uterotrophic analysis, uterus wet and blotted weights, vaginal opening, uterus length of female rats has been recorded at the end of the experiment. For detect of cell response, luminal epithelium height, gland number and lactoferrin intensity in luminal epithelium of uterus were evaluated. Biochemical analysises in blood were performed.Relative uterus weights of rats in 100mg/kg/day dose group of myricetin were statistically increased according to vehicle control and positive control groups. In dose groups of apigenin and phloretin it was found that there were cell responses in uterus. All treatment groups had a significant difference in the high intensity of lactoferrin and uterine gland count compared to oil control group. There was no difference between phloretin and apigenin treatment groups in uterine weight statictically. Uterine heights were increased in positive control groups and 100mg/kg/day dose group of myricetin. Epithelial cell heights were increased in treatment groups except apigenin and phloretin dose groups. There was no difference between all treatment groups in vaginal opening values according to positive control.

Urogenital Schistosomiasis Presenting Genital and Urinary Tract Lesions and Abdominal Discomfort in a Sterile Angolan Woman

Urogenital Schistosomiasis Presenting Genital and Urinary Tract Lesions and Abdominal Discomfort in a Sterile Angolan Woman Background: Schistosomiasis or bilharziasis is a parasitic disease caused by blood fluks of the genus Schistosoma. Schistosoma haematobium has been found in the Middle East, India, Portugal and Africa and it is responsible by urogenital schistosomiasis, pathology with strong economic and health repercussions in the endemic countries. The repercussions of schistosome infection in the health of an Angolan woman are presented and the effects of urogenital schistosomiasis in the human fertility are discussed. Methods: A woman who came to the hospital for gynaecologic consultation because of primary sterility. She presented micturition problems, abdominal discomfort and back pain. Biopsies of the bladder and uterus epithelium showed Schistosoma haematobium ova. The patient was subdued to parasitological, ultrasonographical and cystoscopical examinations and treatment of the schistosomiasis associated to drug to prevent bacterial super-infection. Results: Ultrasonography showed hypertrophy and irregularity of the bladder wall. Hystologic analysis showed S. haematobium eggs in the uterus epithelium and bladder. Cystocopy revealed sandy patches and ulceration at the ureteric meatus. Conclusions: This was the first documented description of female genital schistosomiasis in Angola. Considering that S. haematobium is endemic in Angola, it is expected that a lot of similar cases of urogenital schistosomiasis are occurring in Angola. Then, preventive actions and early treatment of schistosomiasis should be implemented in endemic areas.

Time dependent influence of etonogestrel on the caspase-3 imunereactivity and apoptotic indexes of rat uterus and ovaries

Apoptosis is necessary for the balance between cell proliferation and loss. Thirty-six Wistar-Albino rats were subjected to investigate apoptotic effect of widely used implantable progestins on ovarian and uterine tissues. Rats were divided into 6 groups. In the first five groups, we applied etonogestrel (IMP) subcutaneous implants (n = 30). The rats in groups were sacrificed sequentially every 10 days after application. The rats in the last group (n = 6) were accepted as controls. Apoptotic index (AI) values and Caspase-3 immunereactivities of ovaries and uterus were recorded. In IMP groups, AI and Hscore values in stroma and glandular epithelium of uterus, granulosa and teca-lutein cells of the ovary increased with the longer progesterone exposure. Increase in AI and Hscore values were more prominent after 30 days of exposure for teca-lutein cells of ovary. Progestins increased apoptosis in ovaries and uterus by the longer exposure. Apoptosis increased in ovaries by chronic progesterone exposure. The apoptotic effect of progestin on endometrium is clear but long-term systemic application may lead to alterations in ovarian physiology. We evaluated time dependent apoptotic effect of etonogestrel on reproductive physiology and discussed progestins effect from another point of view in this study.

The long-term apoptotic effects of progesterone-only contraceptives on endometrium and ovary in rats

OBJECTIVE: Apoptosis is necessary for the balance between cell proliferation and cell loss. Various pathologies are related with excessive or deficient apoptosis. We evaluated apoptotic effect of widely used enjectable and implantable progestines on ovarian and uterine tissues via rat study design. DESIGN: Prospective randomise experimental study MATERIALS AND METHODS: Sixtysix Wistar-Albino rats were used. Etonogestrel(IMP) was implanted in 30 rats. Medroksiprogesterone-acetate(MPA) was enjected in another 30 rats. After application of drugs, 6 rats were sacrificed at the each 10th,20th,30th,40th and 50th days. Six rats served as controls. Ovarian and uterine tissues were evaluated for apoptotic index(AI) and caspase-3 immunoreactivity(HSCORE). RESULTS: In both IMP and MPA groups, AI and HScore values in stroma and glandular epithelium of uterus increased with the longer progesterone exposure time. AI and HScore values did not change in endometrium. AI and HScore values also increased with the longer progesterone exposure time in both granulosa and teca-lutein cells of the ovary in IMP and MPA groups. Particularly, increase in AI and HScore values were more prominent after 30 days of progestine exposure for teca-lutein cells of ovary. CONCLUSIONS: Progestine increased apoptosis in ovaries and uterus by the longer exposure time. This effect on uterus is consistent with literature. Apoptotic effect is more prominent by the longer exposure time. Apoptosis increased in ovaries by chronic progesterone exposure which is in contrast with some studies in literature. This effect might be related with chronic supression of gonadotropins and elevation of androgens due to decreased SHBG levels which are indirect effects of progestines. Late reversal of fertility with depot and implant forms of progestines when combined with their apoptotic effects it could be considered that longer duration of progestin usage can cause a shorter period of fertile life.

Localization of gender-regulated gene expression in the filarial nematode Brugia malayi

We used in situ hybridization (ISH) to localize expression of gender-biased genes in the filarial parasite Brugia malayi that were previously identified by microarray analysis and quantitative reverse transcriptase PCR (qRT-PCR). We studied seven genes with male-biased expression, 11 genes with female-biased expression, and one control gene with equal expression in males and females. RNA probes were hybridized to frozen sections of adult worms. ISH confirmed gender-biased expression for all 18 of the differentially expressed genes and non-biased expression for the control. We identified six patterns of expression for these genes. As expected, most of the gender-biased genes were expressed in reproductive organs, developing gametes and embryos. Hybridization signal intensities correlated with relative mRNA levels as assessed by qRT-PCR. Some of the differentially expressed genes had tightly regulated expression patterns. For example, a high mobility group protein gene ( Bm-hmg) was exclusively expressed in developing larvae in females. Expression was first detected in late stage oocytes, peaked in morula stage embryos and no signal was detected in late pretzel stage or in stretched microfilariae. Another female up-regulated gene (microfilarial sheath protein Bm- shp-1) was exclusively expressed in the epithelium of uterine sections that contained morulae or early pretzel embryos. No signal was detected in other female structures, in late embryos or in male worms. This result suggests that microfilarial sheath proteins are produced by the uterus epithelium and not by embryos. Transcripts of the male-upregulated major sperm protein-1 ( Bm-msp-1) were detected in spermatocytes in the early spermatogenesis zone and in spermatids but not in spermatozoa in the vas deferens. Thus, ISH provides a means to independently confirm differential expression of genes identified by other methods. In addition, localization patterns provide insight regarding the function of known or novel genes in the parasite.

A repeated 28-day oral dose toxicity study of methoxychlor in rats, based on the 'enhanced OECD test guideline 407' for screening endocrine-disrupting chemicals.

In association with the international validation project to establish an OECD Enhanced Test Guideline 407, we performed a 28-day repeated-dose toxicity study of methoxychlor, a chlorinated hydrocarbon pesticide with pro-estrogenic and anti-androgenic activities. Attention was paid to the sensitivity of certain additional parameters for detecting endocrine related effects of endocrine disrupting chemicals based on the existing TG 407. Seven-week-old Crj:CD(SD)IGS rats were allocated to one of four groups, each consisting often males and ten females, and methoxychlor was administered once daily by gavage at doses of 0 (control), 20, 100 or 500 mg/kg body weight per day. Male rats were killed on the day after the 28th administration. Female rats were killed on the day of the diestrus stage during 4 days after the 28th administration. Male rats receiving methoxychlor showed mainly atrophy of mammary acinus in the 20 mg/ kg and higher groups, together with decreases in prostate and seminal vesicle weights, and atrophy of epididymis, prostate, seminal vesicle and coagulating gland in the 100 and 500 mg/kg groups. In addition, decrease in serum testosterone level, increase in follicle-stimulating hormone level, decrease in testis and epididymis weights, atrophy of semiferous tubules and Leydig cells, decrease in the number of sperm in the caudal epididymis and their motility were observed in the 500 mg/kg group. Female rats receiving methoxychlor showed mainly abnormal estrous cycles, decrease in serum luteinizing hormone level, decrease in ovary weight, proliferation of mammary acinus, atrophy of ovary due to decrease in follicles and corpus luteum in histopathology, hypertrophy of endometrial epithelium of uterus and vagina epithelium in the 100 and 500 mg/kg groups. Among the parameters tested in the present experimental system, effects of methoxychlor on endocrine-related organs were detected with regard to serum hormone, organ weights, histopathological examination in both sexes, estrus cycle in females and sperm examination in males. Based on these results, a no-observed-adverse-effect level (NOAEL) in the present study was estimated to be below 20 mg/kg per day. In particular, the adverse effects were effectively detected in organ weights of accessory sex organs and histopathological examination.

Ovine uterine gland knock-out model: effects of gland ablation on the estrous cycle.

Ovine endometrial gland development is a postnatal event that can be inhibited epigenetically by chronic exposure of ewe lambs to a synthetic progestin from birth to puberty. As adults, these neonatally progestin-treated ewes lack endometrial glands and display a uterine gland knockout (UGKO) phenotype that is useful as a model for study of endometrial function. Here, objectives were to determine: 1) length of progestin exposure necessary from birth to produce the UGKO phenotype in ewes; 2) if UGKO ewes display normal estrous cycles; and 3) if UGKO ewes could establish and/or maintain pregnancy. Ewe lambs (n = 22) received a Norgestomet (Nor) implant at birth and every two weeks thereafter for 8 (Group I), 16 (Group II), or 32 (Groups III and IV) weeks. Control ewe lambs (n = 13) received no Nor treatment (Groups V and VI). Ewes in Groups I, II, III, and VI were hemihysterectomized (Hhx) at 16 weeks of age. After puberty, the remaining uterine horn in Hhx ewes was removed on either Day 9 or 15 of the estrous cycle (Day 0 = estrus). Histological analyses of uteri indicated that progestin exposure for 8, 16, or 32 weeks prevented endometrial adenogenesis and produced the UGKO phenotype in adult ewes. Three endometrial phenotypes were consistently observed in Nor-treated ewes: 1) no glands, 2) slight glandular invaginations into the stroma, and 3) limited numbers of cyst- or gland-like structures in the stroma. Overall patterns of uterine progesterone, estrogen, and oxytocin receptor expression were not different in uteri from adult cyclic control and UGKO ewes. However, receptor expression was variegated in the ruffled luminal epithelium of uteri from UGKO ewes. Intact UGKO ewes displayed altered estrous cycles with interestrous intervals of 17 to 43 days, and they responded to exogenous prostaglandin F(2 approximately ) (PGF) with luteolysis and behavioral estrus. During the estrous cycle, plasma concentrations of progesterone in intact control and UGKO ewes were not different during metestrus and diestrus, but levels did not decline in many UGKO ewes during late diestrus. Peak peripheral plasma concentrations of PGF metabolite, in response to an oxytocin challenge on Day 15, were threefold lower in UGKO compared to control ewes. Intact UGKO ewes bred repeatedly to intact rams did not display evidence of pregnancy based on results of ultrasound. Collectively, results indicate that 1) transient, progestin-induced disruption of ovine uterine development from birth alters both structural and functional integrity of the adult endometrium; 2) normal adult endometrial integrity, including uterine glands, is required to insure a luteolytic pattern of PGF production; and 3) the UGKO phenotype, characterized by the absence of endometrial glands and a compact, disorganized endometrial stroma, limits or inhibits the capacity of uterine tissues to support the establishment and/or maintenance of pregnancy.

Molecular cloning and amino acid sequence of the porcine 17 beta-estradiol dehydrogenase.

We describe the cloning and sequencing of porcine 17 beta-estradiol dehydrogenase. The enzyme performs oxidation 360-fold more efficiently than reduction, both measured under optimal conditions. It is localized in specialized vesicles of epithelial cells. The cDNA clones were isolated from a lambda UNI ZAP XR library of porcine kidney and polymerase-chain-reaction-amplified from templates of uterus epithelium. In both tissues, the same enzyme is coded by a transcript of 2.9 kb. It contains a 69-b 5'-noncoding region, an open reading frame of 2211 b and a 3'-noncoding region of 624 b. The open reading frame of 737 amino acids with a predicted molecular mass 79,973 Da was confirmed by amino acid sequencing of peptides. The 80-kDa translation product is processed to the N-terminal 32-kDa enzyme, part of which is then covalently linked to actin. The estradiol dehydrogenase/actin complex and the 80-kDa translation product comigrate in SDS/PAGE.

Differentially regulated immediate early genes in the rat uterus

Estrogen stimulates cellular proliferation in the luminal epithelium, stroma, and smooth muscle of immature rat uterus. Progesterone administered concurrently with estrogen blocks the stimulatory effect of estrogen specifically in the epithelium, whereas progesterone administered alone stimulates proliferation in the endometrial stroma and myometrium. The present studies determined the effects of estrogen and progesterone on expression of the growth-associated, immediate early genes c-fos, c-jun, and jun-B in the luminal epithelium of the uterus. Hormonal effects were quantitated by Northern analysis of RNA extracted directly from the uterine luminal epithelium. Estrogen stimulated c-fos and jun-B expression, but repressed c-jun mRNA levels in the epithelium. In contrast, when whole organ RNA extracts were analyzed, estrogen increased mRNA levels for all three genes. Although progesterone administered alone showed no effect on mRNA levels in either epithelial or whole uterus extracts, it did attenuate the estrogen-induced increase in c-fos mRNA by 50% in whole uterus extracts and by 23% in epithelial extracts. The estrogen-induced increase in epithelial jun-B mRNA was not affected by progesterone pretreatment. Thus, in the immature rat uterus, no simple correlation exists between cellular proliferation and increased expression of the genes studied. However, progesterone completely blocked the repressive effect of estrogen on epithelial c-jun, suggesting a link between decreased c-jun expression and induction of cell proliferation in the uterine luminal epithelium. Estrogen repression of epithelial c-jun expression was hormone specific and sensitive to antiestrogen blockade. After estrogen treatment, epithelial c-jun mRNA decreased with a rate similar to its half-life, as determined in primary cultures of rat uterine cells. These results suggest that estrogen, acting through its receptor, directly represses transcription of c-jun in the uterine epithelium. Differences in hormonal regulation of immediate early genes between epithelial and nonepithelial uterine tissues probably results from tissue-specific transactivating factors that control the expression of these genes.

Epidermal growth factor (EGF) replaces estradiol for the initiation of embryo implantation in the hypophysectomized rat

Several studies have provided evidence that epidermal growth factor (EGF) or transforming growth factor alpha (TGF alpha) mediate some of the physiological effects of estrogen. The object of the present study was to determine whether exogenous EGF could initiate embryo implantation in the rat, a response known to depend upon the action of estrogen in a progesterone-primed uterus. Immunocytochemical examination showed the presence of immunoreactive EGF, TGF alpha and the EGF receptor in luminal glandular epithelium of uteri on days 4,5 and 6 of pregnancy. EGF receptor was also present in the implanting embryo and in decidual cells of the uterine stroma. Attempts to initiate implantation by intravenous injection of murine EGF into ovariectomized or hypophysectomized delayed-implanting rats maintained with progesterone were unsuccessful. Implantation sites were found, however, in 24 of 33 (73 per cent) hypophysectomized progesterone-primed rats given 100 micrograms EGF immediately after intrauterine transfer of blastocysts from hypophysectomized delayed implanting animals. Although EGF is capable of initiating implantation in the delayed implanting rat model it remains to be determined whether this growth factor is responsible for the implantation inducing action of estrogen in vivo.

Studies in the in vivo expression of the influenza resistance gene Mx by in-situ hybridisation

The inbred laboratory mouse strain A2G carries a functional, interferon type 1 inducible gene, Mx which upon expression confers specific resistance to an otherwise lethal dose of influenza virus. We investigated in vivo Mx gene expression by performing Northern hybridisation and in-situ hybridisation on A2G (Mx+) and (CBA/J x C57)F1 (Mx-) mice that were induced either with human, natural interferon; human, recombinant interferon or double stranded poly(I):(C). All 3 inducers were able to stimulate Mx expression in all organs examined in the A2G strain. However, contrary to previous reports, Mx expression was confined to a small number of cell types; the main contributor was most probably mononuclear cells. Specialised cells such as hepatocyte, nephron, ovarian follicle and seminiferous tubules did not show detectable Mx level. There was also constitutive Mx expression in the epithelia of uterus and duodenum which suggested direct gene activation independent of blood-bourne interferon.

Multidrug resistance gene expression is controlled by steroid hormones in the secretory epithelium of the uterus

The multidrug resistance (mdr) gene family has been shown to encode a membrane glycoprotein, termed the P-glycoprotein, which functions as a drug efflux pump with broad substrate specificity. This multigene family is expressed in a tissue-specific fashion in a wide variety of normal and neoplastic tissues. The regulation of mdr gene expression in normal tissues is not understood. We have recently shown that mdr mRNA and the P-glycoprotein increases dramatically in the secretory luminal and glandular epithelium of the gravid murine uterus. This observation has suggested that mdr gene expression in the uterus is controlled by the physiologic changes associated with pregnancy. This report now demonstrates that mdr mRNA and P-glycoprotein are induced at high levels in the uterine secretory epithelium by the combination of estrogen and progesterone, the major steroid hormones of pregnancy. This regulation of mdr gene expression in the uterus does not require any other contribution from the fetus or placenta. The data indicate that this gene locus is hormonally responsive to estrogen and progesterone in the uterine secretory epithelium, suggesting an important and physiologically regulated role during pregnancy.

The gene encoding multidrug resistance is induced and expressed at high levels during pregnancy in the secretory epithelium of the uterus.

A survey of the expression of the multidrug-resistance gene (mdr) in mouse tissues revealed that a mdr mRNA species is expressed at extremely high levels in the gravid uterus. mdr mRNA expression levels increase dramatically during pregnancy compared to the relatively low levels of expression observed in the nongravid uterus. In situ hybridization experiments revealed that the increased expression of the mdr mRNA is specifically localized to the secretory epithelial cells of the endometrium. Immunocytochemistry studies with a mdr glycoprotein-specific antiserum demonstrate that the mdr glycoprotein is predominantly localized to the luminal surface of the secretory epithelial cells. These results indicate that the mdr gene expression in the uterus is controlled by the physiologic changes associated with pregnancy. Our data are consistent with a potential role for the mdr glycoprotein in the transport of substrate across the secretory epithelium of the gravid uterus.

Implantation in the rabbit: ultrastructural features of nuclei involved in symplasm formation.

Mitoses, direct division or cell fusion are observed during symplasm formation in the rabbit uterus epithelium. These phenomenon are examined through transmission electron-microscopic studies. Two types of direct division are described: (1) nuclear scission after folding of the membrane and (2) nuclear scission by invagination of the membrane. The existence of amitoses has long been contested in mammals; the present study tends to show that direct division is not an accidental karyorrhexis but is organized at the cellular level.