Effects of age, nursing, and oral IGF1 supplementation on neonatal porcine cervical development.

Nursing supports neonatal porcine uterine and testicular development, however, lactocrine effects on cervical development are undefined. Studies were conducted to determine the effects of i) age and the imposition of the lactocrine-null state from birth (postnatal day 0 (PND0)) by milk replacer feeding on cervical histology; ii) imposition of the lactocrine-null state for 2 days from birth on cervical cell proliferation, as reflected by proliferating cell nuclear antigen immunostaining; and iii) a single feeding of colostrum or milk replacer, administered at birth, with or without oral IGF1, on cervical cell proliferation and phosphorylated AKT (pAKT) and B-cell lymphoma 2 (BCL2) protein levels at 12 h postnatal. Cervical crypt depth and height of luminal epithelium (LE) increased with age by PND14, when both responses were reduced in replacer-fed gilts. Cell proliferation was reduced in LE at PND2, and in crypt epithelium and stroma by PND14 in replacer-fed gilts. Returning replacer-fed gilts to nursing on PND2 did not rescue the cervical phenotype by PND14. A single feeding of colostrum, but not milk replacer, was sufficient to support cervical cell proliferation at 12 h postnatal. IGF1 supplementation induced cell proliferation in replacer-fed gilts, and increased cervical pAKT and BCL2 levels in colostrum-fed gilts and replacer-fed gilts at 12 h postnatal. Results indicate that age and nursing support porcine cervical development, support is initiated at first ingestion of colostrum, IGF1 may be lactocrine-active, and identification of lactocrine-active factors can be accomplished by 12 h postnatal using this bioassay system.

The developmental origin of cervical and vaginal epithelium and their clinical consequences: a systematic review.

OBJECTIVE: Studies on the development of the embryological and fetal development of the cervix and the vagina are rare and mostly go back to the first decades of the last century. The aims of this review were to present the latest knowledge concerning the developmental origin of cervical and vaginal epithelium and to point out new results in the context of different clinical findings. MATERIALS AND METHODS: Relevant studies published between 1910 and 2013 were identified via PubMed, MEDLINE, OVID, Web of Science, and EMBASE. The reference lists of retrieved articles were reviewed to locate additional articles. Each abstract was reviewed, and the appropriate publications were obtained and reviewed as well. A total of 33 articles and 8 book chapters were selected for citation in this review. RESULTS: New objective findings clearly show that human prenatal epithelialization of the cervix and vagina results in 3 morphogenetically determined units: (i) the Müllerian columnar epithelium of the endocervix, (ii) the Müllerian squamous epithelium of the ectocervix and the upper vagina, and (iii) the vaginal squamous epithelium of the lower vagina. CONCLUSIONS: These results are of high clinical relevance and may provide new insight into the histogenesis of ectopy, vaginal adenosis, and the congenital transformation zone. They should be added to the explanations in gynecological, colposcopical, and gynecopathological textbooks.

Efficient synthesis of a novel m-phenylene derivative as a selective EP4 agonist inducing follicular growth and maturation in the ovary.

An efficient and straightforward synthesis of a novel m-phenylene derivative has been developed. The optically pure dibromo compound was selected as a starting material. Through a protocol involving the Prins reaction and two steps of the Horner-Wadsworth-Emmons reaction, the basic skeleton was constructed with appropriate alpha and omega side chains. The compound proved to be a highly selective EP(4) agonist and a possible drug candidate for maturation of the uterine cervix.

Growth-profile configuration for specific deformations of tubular organs: A study of growth-induced thinning and dilation of the human cervix.

Growth is a significant factor that results in deformations of tubular organs, and particular deformations associated with growth enable tubular organs to perform certain physiological functions. Configuring growth profiles that achieve particular deformation patterns is critical for analyzing potential pathological conditions and for developing corresponding clinical treatments for tubular organ dysfunctions. However, deformation-targeted growth is rarely studied. In this article, the human cervix during pregnancy is studied as an example to show how cervical thinning and dilation are generated by growth. An advanced hyperelasticity theory called morphoelasticity is employed to model the deformations, and a growth tensor is used to represent growth in three principle directions. The computational results demonstrate that both negative radial growth and positive circumferential growth facilitate thinning and dilation. Modeling such mixed growth represents an advancement beyond commonly used uniform growth inside tissues to study tubular deformations. The results reveal that complex growth may occur inside tissues to achieve certain tubular deformations. Integration of further biochemical and cellular activities that initiate and mediate such complex growth remains to be explored.

Collagen, glycosaminoglycans and matrix metalloproteinase-2 and metalloproteinase-9 in the cervix of the ewe during prepubertal development.

The tortuous nature of the ovine cervix restricts the transcervical passage of the cannula, and many studies have aimed to understand the endocrine mechanism of the remodelling of cervical tissue in adult ewe. However, little is known about the remodelling of the cervical tissue during the prepubertal development of the lambs. To obtain histochemical and biochemical evidence about the nature of the prepubertal development of the cervix of the ewe, cervices of Corriedale lambs obtained at 0, 1, 2, 4, 6 and 8 months of age (n = 5 to 6 in each) were processed. Neutral and acidic glycosaminoglycans (by PAS-Alcian stain) were weakly in the cervical stroma and not shown change during the development, whereas the percentage volume of fibrillar collagen (by van Gieson stain) increases throughout the experimental period in the superficial fold stroma and deep wall stroma (p < 0.05). The relative cervical weight (g/kg of body weight) and the collagen concentration (by spectrophotometry, mg/mg wet tissue) showed an early decreasing phase from months 0 to 4 and a later increasing phase from months 4 to 8 (p < 0.05). The latent form of matrix metalloproteinase-2 (MMP-2) detected by gelatin zymography (ng/mg protein) decreased from months 0 to 2 and increased from months 4 to 8, whereas the activated form decreased from months 0 to 2, remained low until month 6 and then recovered on month 8 (p < 0.0001). Data suggest that the relative cervical weight biphasic pattern during the development is related to MMP-2-dependent changes in the collagen content.

[Study on the estrogenic effects of isoflavone].

OBJECTIVE: The study aimed to investigate the endocrine disruptive toxicity of isoflavone in vivo, through comparing with genistein, to study main active parts of isoflavone in estrogenic active, also. METHODS: Uterotrophic assay was carried out. 0.1, 0.2, 0.5, 1.5 g/kg bw isoflavone, 0.05, 0.10, 0.25, 7.50 g/kg bw genistein, 3.0 microg/kg estradiol as positive control, water and oil as control were respectively administered orally to the animal for 3 consecutive day. In the end of the test, uterine wet and blotted weight, histopathology of ovary, uterus and vaginal were measured. Finally, all the effects caused by isoflavone and geinistein were compared. RESULTS: Both isoflavone and genistein induce uterine weight increase significantly; histopathology of uterus and vagina showed that both isoflavone and genistein induce proliferation; there are dose-response relationship; in the related dose level, isoflavone and genistein caused similar effects. CONCLUSION: In uterotrophic assay, genistein was the main active part of isoflavone; via oral administration to immature prepuberty rat, isoflavone had endocrine disruptive effects which had obviously dose-response relationship.

Evidence that relaxin's effects on growth and softening of the cervix are not mediated through prostaglandins in the rat.

Relaxin plays a major role in promoting the growth and softening of the cervix that occurs during the second half of pregnancy in the rat. There is limited evidence that prostaglandins play a role in cervical softening in mammalian species. Accordingly, this study was conducted to determine if prostaglandins mediate relaxin's effects on the rat cervix. To attain that objective, indomethacin was used to inhibit cyclooxygenase, the key enzyme in the conversion of arachidonic acid to prostaglandins. Twenty-six nonpregnant female rats were ovariectomized when they were 78 days old (day 1 of treatment). At ovariectomy (O), each rat was fitted with silicon tubing implants containing progesterone (P) and estrogen (E) in doses that provided blood levels similar to those during late pregnancy in rats. Rats were randomly assigned to three treatment groups. Group OPE controls (n = 8 rats) received 2 ml indomethacin vehicle (0.5% methyl cellulose, 0.025 Tween 80 in water) via gavage at 0900 h on days 8 and 9 and 0.5 ml relaxin vehicle (0.9% NaCl) s.c. at 6-h intervals from 1200 h on day 8 through 0600 h on day 10. Group OPER (n = 9 rats) was treated as group OPE except that 20 microg highly purified porcine relaxin was administered. Group OPERI (n = 9 rats) was treated as group OPER except that indomethacin was administered at a dose (20 mg/kg BW) that reduced cervical PGE2 levels by more than 90%. Between 0800 h and 1000 h on day 10, the cervices were removed, trimmed of fat, weighed, and placed in ice-cold Krebs-Ringer bicarbonate buffer, pH 7.5. Cervical extensibility (degree of softening) was determined within 4 h of tissue collection. Both the mean cervical wet weight and the mean cervical extensibility in the relaxin-treated group OPER rats were markedly greater (P < 0.01) than in the group OPE controls. Treatment with indomethacin did not diminish relaxin's effects on either cervical wet weight or cervical extensibility. In conclusion, this study provides evidence that relaxin's effects on cervical growth and softening in the rat are not mediated through prostaglandins.

Relaxin increases secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 during uterine and cervical growth and remodeling in the pig.

Matrix metalloproteinases are proteolytic enzymes that degrade the extracellular matrix and are essential for tissue remodeling. Uterine and cervical growth require remodeling of structural barriers to cell invasion and matrix metalloproteinase-2 and -9 degrade type IV collagen, the major component of basement membranes. Relaxin stimulates uterine and cervical growth and remodeling, which includes remodeling of support elements such as basement membranes. The objective of this study was to determine whether relaxin alters the production and/or activity of matrix metalloproteinase-2 and -9 in the uterus or cervix of the pig. The growth-promoting effects of relaxin were elicited by administering relaxin to prepubertal gilts every 6 h for 54 h. The expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 was characterized by gel zymography, and proteins were quantified by immunoblotting. Total enzyme activity was measured using matrix metalloproteinase-specific fluorescent substrate assays. In both uterine and cervical tissues, immunoreactive matrix metalloproteinase-2 and matrix metalloproteinase-9 protein expression was similar in relaxin-treated and control animals. However, tissue-associated gelatinase activity was attenuated by relaxin (P < 0.05). In contrast, relaxin significantly increased the secretion of active matrix metalloproteinase-2 and -9 protein into uterine fluid (P < 0.05). Given the importance of matrix metalloproteinases in extracellular matrix degradation, the observation that relaxin promotes uterine secretion of matrix metalloproteinase-2 and -9 supports the concept that relaxin facilitates the growth and remodeling of reproductive tissues by increasing extracellular proteolysis in the pig reproductive tract.

Relaxin increases secretion of tissue inhibitor of matrix metalloproteinase-1 and -2 during uterine and cervical growth and remodeling in the pig.

Remodeling of reproductive organs during pregnancy requires degradation and resynthesis of structural barriers to cell invasion. Matrix metalloproteinases (MMPs) are enzymes that break down components of the extracellular matrix (ECM) and are essential for tissue remodeling processes. Tissue inhibitors of metalloproteinases (TIMPs) are important regulators of MMP activity. In the pig, relaxin stimulates growth and remodeling of the uterus and cervix during pregnancy, effects that include the ability to alter elements of the ECM. Therefore, the objective of this study was to determine whether relaxin alters the production and/or activity of TIMP-1 and TIMP-2 in the porcine uterus or cervix. The growth-promoting effects of relaxin were elicited by administering relaxin to prepubertal gilts every 6 h for 54 h. Expression of TIMP-1 and TIMP-2 was characterized by immunoblotting. Total enzyme activity was measured using an MMP-specific fluorescent substrate assay. TIMP-1 and TIMP-2 proteins were present in the uterus and cervix of control and relaxin-treated pigs, and both proteins were increased by relaxin in the uterine flushes and tissues (P < 0.05). Inhibitor activity in uterine tissue extracts and uterine flushes from relaxin-treated animals was greater than that in controls; however, this activity was restricted to inhibition of MMP-2. In the uterine cervix, relaxin enhanced expression of TIMP-1 and TIMP-2 (P < 0.05), whereas expression of both TIMP proteins was similar in the vaginal cervix of control and relaxin-treated animals. Likewise, inhibitor activity against MMP-2 in the uterine cervix was enhanced in response to relaxin (P < 0.05). In contrast, inhibitor activity was attenuated in extracts from the vaginal cervix (P < 0.05). This study highlights the complex nature of MMP/TIMP regulation during reproductive tissue growth and suggests that TIMP-1 and TIMP-2 may be involved in other aspects of the growth process. These data support a role for relaxin in regulating the activity of TIMPs during growth and remodeling of reproductive connective tissue.

Strain differences in the ontogeny of estrogen receptors in murine uterine epithelium.

The expression of estrogen receptor (ER) in the reproductive tracts of neonatal mice was examined using immunocytochemical and autoradiographic methods. Two strains of mice used in previous studies that reported contradictory results showed different rates of uterine epithelial development. In the inbred strain, BALB/c, the epithelium was devoid of receptor from birth through 5 days of age, while uterine epithelial cells of the outbred strain, CD-1, expressed ER as early as 3 days of age. Oviductal epithelium and cervical epithelium expressed ER on the day of birth in CD-1 mice. Glandular ontogeny in the uteri of CD-1 animals was also advanced by 3 days compared to that of BALB/c mice. These observations reconcile the conflicting reports of ER ontogeny in the neonatal mouse. More importantly, these results confirm our earlier observations, indicating that the cells lining uteri of 2- and 4-day-old BALB/c mice lack ER at a time when estrogen induces their proliferation.

Progesterone regulates epidermal growth factor receptor on mucous secreting cells in the rabbit endocervix.

During postnatal differentiation, epidermal growth factor (EGF) receptor is expressed by all major cell types of the cervix. Computer-assisted image analysis confirmed the highest concentration of EGF receptor is in the epithelial cells. Flow cytometric analysis of subpopulations of epithelial cells from estrous rabbits showed the mucous secreting cells had the highest concentration of EGF receptor, i.e. 1-1.5 x 10(5) receptors per cell. Because the mucous secreting cells are targets for steroid hormones it seemed likely that steroids regulate EGF receptor expression. To investigate this possibility, hormone-dependent changes in EGF receptor expression were quantified by flow cytometry. Ovariectomy and the treatment of ovariectomized animals with estradiol altered forward angle light scatter and side scatter signals which correlated with cell size and secretory granule content, respectively. However, the number of epithelial cells and the number of EGF receptors per cell were unaffected. Progesterone treatment of ovariectomized animals dramatically reduced the number of EGF receptors on the mucous secreting cells, accounting for a 43% reduction in the total EGF receptor content of the epithelium. The treatment of neonates with diethylstilbestrol did not change the number of EGF receptors in endocervical epithelial cells when examined in adulthood. However, the number of mucous secreting cells was decreased, thereby reducing the EGF receptor content of the epithelium 19-36% compared to estrous and estradiol-treated animals. These results provide the first evidence that progesterone regulates EGF receptor on mucous secreting cells in the endocervix and that diethylstilbestrol treatment alters the EGF receptor content of the epithelium by altering its cellular composition.

Growth-promoting effects of relaxin and related compositional changes in the uterus, cervix, and vagina of the rat.

Although the precise role of relaxin has yet to be elucidated, it has been implicated in the regulation of physiological and biochemical processes in the reproductive tract during pregnancy and parturition. In this study, the growth-promoting effects of relaxin and related compositional changes in the uterus, cervix, and vagina of immature ovariectomized estrogen-primed rats were examined. Relaxin increased the wet weight of the uterus, cervix, and vagina in a significant and linear manner over the log of the dose range (1-30 micrograms; 6 h). The increase in uterine weight was due to increases in both dry weight and water content at all doses. A dose of 1 microgram relaxin induced maximal increases in dry weights in the cervix and vagina over control values; higher doses increased wet weight, but these changes were due solely to increases in water content. Thirty micrograms of relaxin were found to increase total soluble protein and glycogen content of the vagina above control values after 6 h. Relaxin did not alter the total collagen levels of the uterus or cervix, and collagen concentrations were significantly reduced in these organs 6 and 24 h after treatment. Total glycosaminoglycan levels were elevated by relaxin in the uterus (6 h) and cervix (24 h). Total vaginal collagen was increased 24 h after relaxin injection, but the collagen concentration was decreased over the time interval studied, and glycosaminoglycan levels in the vagina were unaltered. In summary, relaxin stimulates growth of the uterus, cervix, and vagina by increasing water content and tissue mass. The increases in distensibility that relaxin induces in these organs appear to be related to changes in the fluid matrix and proteoglycan metabolism rather than alterations in collagen concentration, at least 6-24 h after a single injection. These results support the hypothesis that relaxin plays a significant role in the maintenance of pregnancy through its contribution to fetal accommodation and in the facilitation of parturition through expansion of the entire birth canal.

Estrogen regulation of the central enzymes involved in O- and N-linked glycoprotein assembly in the developing and the adult rabbit endocervix.

During cervical differentiation in 1- to 6-month-old rabbits, a marked increase was observed in the titer of serum estradiol, the number of secretory cells in the endocervix, and the granule content of these cells. Because these secretory granules are rich in carbohydrates it seemed likely that hormones regulate glycoconjugate biosynthesis in the endocervix. To investigate this possibility, the synthesis of O- and N-linked glycoproteins was studied in cell-free preparations from endocervical epithelium. The activity of N-acetylgalactosaminyl (GalNAc) transferase, the first enzyme in the pathway for O-linked oligosaccharide chain biosynthesis, measured in microsomes prepared from the developing cervix, was increased 8-fold. Oligosaccharyltransferase, the enzyme that catalyzes the first step in the attachment of N-linked oligosaccharide chains to proteins, was measured in microsomes prepared under the same conditions as those used for GalNAc transferase. The results of two independent assay methods revealed an estrogen-dependent 10- to 15-fold increase in oligosaccharyltransferase during cervical differentiation. Consistent with these developmental effects, ovariectomy of adult rabbits resulted in reduced (P less than 0.01) titers of serum estradiol and a 2-fold reduction in the specific activity of GalNAc transferase. When animals were treated with exogenous estradiol, GalNAc transferase activity returned to estrous control levels. The antagonistic action of progesterone on GalNAc transferase activity was verified using endocervical membranes from pseudopregnant animals. Similarly, oligosaccharyltransferase activity was reduced 2- to 3-fold when estrous animals were ovariectomized or made pseudopregnant. The treatment of ovariectomized animals with estradiol resulted in the restoration of oligosaccharyltransferase to estrous control values. Collectively, these results provide the first definitive evidence that hormones can regulate the activity of the enzymes involved in the attachment of O- and N-linked oligosaccharide chains to proteins in the endocervix.

Inhibition of nitric oxide synthase activity diminishes the acute effects of relaxin on growth, but not softening, of the cervix in the rat.

Relaxin promotes growth and softening of the cervix during pregnancy in the rat. This study examined the hypothesis that nitric oxide (NO) mediates the effects of relaxin on the rat cervix. To test that hypothesis, N omega-nitro-L-arginine methyl ester (L-NAME) was used to inhibit NO synthase, the enzyme that converts arginine to NO and L-citrulline. Nonpregnant rats were ovariectomized when they were 78 days old (day 1 of treatment). At ovariectomy each animal was fitted with silicon tubing implants containing progesterone (P) and estrogen (E) in doses that provide blood levels similar to those during late pregnancy. Rats were assigned to three treatment groups. The control group OPE (n = 6 rats) received 0.5 ml L-NAME vehicle (PBS) sc at 6-h intervals from 0600 h on day 7 through 1200 h on day 8 and 0.5 ml relaxin vehicle (PBS) sc at 0600 and 1200 h on day 8. Group OPER (n = 6 rats) was treated in the same way as group OPE, except that 20 microg porcine relaxin were administered. Group OPERI (n = 7 rats) was treated in the same way as group OPER, except that L-NAME was administered at a dose of 100 mg/kg x 6 h. Between 1400-1500 h on day 8, the cervices were removed and weighed. Cervical wet weight and extensibility were markedly greater (P < 0.01) in relaxin-treated group OPER rats than in group OPE controls. Treatment with L-NAME diminished relaxin's effects on cervical wet weight, but not cervical extensibility. In conclusion, this study provides evidence that NO contributes to the acute effects of relaxin on the growth, but not the softening, of the rat cervix.

Developmental pattern of estrogen receptor expression in female mouse genital tracts.

The distribution of the estrogen receptor (ER) was investigated in neonatal female genital tracts (uterus, oviduct, cervix, and vagina) from days 1-22 after birth, using immunohistochemistry employing an anti-ER monoclonal antibody. In uteri, the ER in epithelial cells began to be observed by day 4. The number of positive epithelial cells and the staining intensity gradually increased until day 22 of age. On the other hand, uterine stroma cells gave a strong ER immunostaining even on day 1. The staining intensity reached a maximum by days 4-7 and then slightly decreased with age. In the oviduct, cervix, and vagina, epithelial cells showed positive ER immunostaining on day 1, and the intensity increased gradually until day 22. ER immunostaining in stroma cells was almost constant during the development period. The ER in both epithelial and stroma cells from these younger animals showed similar biochemical properties, i.e. an increased affinity for nuclei and resistance to extraction with PBS. Thus, during neonatal development of the female reproductive tract, ER is present not only in stroma cells but also in epithelial cells. This ER protein exhibits properties and characteristics similar to those of adult mice. The presence of ER suggests that some of the estrogen actions of cell proliferation, differentiation, and tissue abnormalities resulting from prenatal and postnatal estrogen administration may be mediated by receptor interactions.

Steroid receptors in the developing and the adult rabbit endocervix and in endocervical epithelial cells isolated by flow cytometry.

Immunocytochemistry with monoclonal antibodies H222 and JZB39 was used to study nuclear estrogen (ER) and progesterone (PgR) receptors, respectively, in the cervix during differentiation and in the adult rabbit. The undifferentiated state of the cervix of 2-week-old rabbits correlates with a paucity of immunoreactive nuclear ER, while the epithelium of most of these animals showed moderate immunostaining for the nuclear PgR. The cervical epithelium, stroma and muscle cells of 1-month-old rabbits, showed weak immunostaining for the ER, while staining for PgR remained comparable to that of 2-week-old rabbits. For 2-4-month old rabbits the epithelium was characterized by moderate immunostaining for the nuclear ER and strong immunostaining for the PgR. Strong, heterogeneous immunostaining for nuclear ER and PgR receptors in endocervical epithelial cells from 6-month-old (adult), estrous rabbits suggested there are subpopulations of cells that express differential sensitivity to steroid hormones. In order to characterize such subpopulations, live endocervical epithelial cells were sorted with a flow cytometer on the basis of forward angle light scatter (FSC) and side scatter (SSC) signals which correlated with cell size and secretory granule content, respectively. Secretory cells, as verified by ultrastructural analysis and histochemical staining, expressed the highest FSC and SSC signals and were designated fraction "a". Changes in the hormonal status of the animals altered the intrinsic light scatter properties of fraction "a" cells as follows: maximum FSC and SSC signals were reported for cells from estrous animals; ovariectomy or progesterone-dominance decreased cell size (FCS) and secretory granule content (SSC), while treatment of ovariectomized rabbits with estradiol increased both parameters. When fraction "a" cells from estrous rabbits were incubated with the monoclonal antibodies, two distinct subpopulations of secretory cells were identified by intensity and pattern of nuclear staining for the ER and PgR. Changes in the hormonal status of the animals produced changes in the intensity of nuclear immunostaining, however both cell types remained distinguishable on the basis of immunostain pattern reflecting either permanent or transitory differences in them, and differential hormone sensitivity. The presence of nuclear ER and PgR proteins in these cells confirms their function is bireceptor-mediated.

Distribution and cyclic change of aromatase cytochrome P-450 activity in human uteri.

Activities of aromatase cytochrome P-450 in the columnar epithelial region (CE), squamous epithelial region (SE) and connective tissue (CT) of uterine cervix, and endometrium (EM) during the menstrual cycle were determined using [4-14C] and [1 beta-3H]androstenedione. Aromatase activities in the proliferative phase (n = 8) were 15.0 +/- 7.9, 10.9 +/- 10.3, 9.4 +/- 10.6 and 8.0 +/- 7.3 (mean +/- SD) fmol/h/mg protein in CE, SE, CT and EM, respectively, and aromatase activities in the secretory phase (n = 6) were 31.5 +/- 7.6, 19.1 +/- 7.1, 5.6 +/- 4.6 and 6.3 +/- 1.5 fmol/h/mg protein, respectively. The results show that the aromatase activities in these regions in the proliferative phase were not significantly different from each other. On the other hand, the aromatase activity in the secretory phase was significantly higher in CE than in any other regions (P less than 0.05), and significantly higher in SE than in CT or EM (P less than 0.05). There was no significant difference in aromatase activity between CT and EM. By comparison of aromatase activity between these two phases, the activity in CE was significantly higher in the secretory phase than in the proliferative phase (P less than 0.05), but no significant difference was observed in other regions.

The Cervical Epithelium From Fetal Age to Adolescence.

Uteri obtained at the postmortem examination of 164 girls ranging in age from premature and immature infants to 11 years were studied for evidence regarding the developmental changes that take place in the cervix during this period of life and in particular the mechanisms involved in the production and regression of congenital ectropion. Tt is concluded that congenital ectropion is a normal feature of development of the cervix.Its occurrence and its persistence or disappearance appear to depend on variable growth of cervical tissues as they react to hormonal stimulation, hormonal deprivation, and systemic growth. The mechanisms are described in detail.

Maturational changes in sympathetic and sensory innervation of the rat uterus: effects of neonatal capsaicin treatment.

The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.