Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse uterus and vagina

Both the uterus and vagina develop from the Müllerian duct but are quite distinct in morphology and function. To investigate factors controlling epithelial differentiation and cell proliferation in neonatal uterus and vagina, we focused on Hedgehog (HH) signaling. In neonatal mice, Sonic hh (Shh) was localized in the vaginal epithelium and Indian hh (Ihh) was slightly expressed in the uterus and vagina, whereas all Glioma-associated oncogene homolog (Gli) genes were mainly expressed in the stroma. The expression of target genes of HH signaling was high in the neonatal vagina and in the uterus, it increased with growth. Thus, in neonatal mice, Shh in the vaginal epithelium and Ihh in the uterus and vagina activated HH signaling in the stroma. Tissue recombinants showed that vaginal Shh expression was inhibited by the vaginal stroma and uterine Ihh expression was stimulated by the uterine stroma. Addition of a HH signaling inhibitor decreased epithelial cell proliferation in organ-cultured uterus and vagina and increased stromal cell proliferation in organ-cultured uterus. However, it did not affect epithelial differentiation or the expression of growth factors in organ-cultured uterus and vagina. Thus, activated HH signaling stimulates epithelial cell proliferation in neonatal uterus and vagina but inhibits stromal cell proliferation in neonatal uterus.     

A case of blind vagina in a crossbred Lusitano mare

This report describes a case of blind vagina diagnosed during a pre-breeding evaluation of a 5-year-old crossbred Lusitano mare. This mare was mated twice during the previous breeding season but remained open. Clinical evaluation revealed the existence of follicles in the ovaries and an enlarged uterus. An ultrasound examination showed that a granular free-floating fluid distended the uterus. No connection was detected between the uterus and the vagina and a presumptive diagnosis of congenital vaginal obstruction was raised. On vaginal examination it was noticed that the vagina was short in depth and ended as a blind pouch. The typical cervical morphology was not observed. Careful evaluation of the clinical situation, both during the follicular and the luteal phases of the mare's oestrous cycle, lead to a diagnosis of segmental aplasia of the cranial vagina. The mare had a normal karyotype on cytogenetic examination [64XX].     

Fine structure of the genital system in the females of Pergamasus mites (Acari: Gamasida: Pergamasidae)

The female reproductive system in Pergamasus mites consists of an unpaired vagina, vaginal duct, uterus, and ovary. Additionally, there are paired vaginal glands, as well as unpaired ventral and paired lateromedial glandular complexes. The vagina and vaginal duct are cuticle‐lined. In the dorsal wall of the vagina, this lining forms the endogynium which possesses a “sac” and two conspicuous “spherules” and is armed with “stipula” and other cuticular protrusions. The endogynium functions as a spermatheca, being a storing site for the spermatophore. The spherule procuticle is perforated by microvilli of underlying cells that are structurally very unusual. The lining of the vaginal duct forms numerous cuticular fibers directed toward the vagina. There is an external layer of muscles, supposedly functioning as a sphincter. The uterus is an organ in which the fertilized egg is stored for some time and starts embryonic development. Its wall is composed of glandular epithelial cells. The ovary consists of inner and outer parts. The former part is formed by a nutritive syncytium, whereas the latter contains growing oocytes. Two groups of glands connect with the genital tract. Paired vaginal glands are composed of glandular and secretion‐storing parts and open into the vagina. Paired lateromedial and unpaired ventral glandular complexes empty into the genital tract between the vaginal duct and uterus. The structure of the female genital system is discussed in terms of its function and phylogeny. J. Morphol. 240:195–223, 1999. © 1999 Wiley‐Liss, Inc.     

Nitric oxide synthase in the rabbit uterus and vagina: hormonal regulation and functional significance

The effects of estrogen (E(2)), progesterone (P(4)), and E(2) and P(4) (E(2)+P(4)) on uterine, vaginal, and cerebellar nitric oxide synthase (NOS) were examined. Additionally, experiments were done to investigate whether NOS-containing nerves were present in the uterus and vagina and the extent to which vaginal smooth muscle response was dependent on nitric oxide (NO). Cytosolic NOS was determined by the formation of [(14)C]citrulline from [(14)C]arginine, and NOS localization was visualized by immunohistochemistry. Vaginal smooth muscle relaxation was induced by electrical field stimulations (EFS). NOS activity in the uterus was markedly down-regulated in all hormone-treated groups. Vaginal NOS activity was nearly 4-fold higher than the uterine NOS activity and was considerably reduced by E(2) or E(2)+P(4) treatment. In contrast to findings in the uterus, P(4) treatment up-regulated vaginal NOS. Hormone treatment had no significant effect on cerebellar NOS. NOS-containing nerves could be demonstrated in the uterus and vagina by immunohistochemistry. Vaginal smooth muscle responded with relaxation after EFS, which was inhibited by N(G)-nitro-L-arginine. A relatively high vaginal NOS, a down-regulation by E(2), an up-regulation by P(4), and NO-dependent response of vaginal smooth muscle suggest a tissue-specific physiological role.     

Prolonged antioestrogenic activity of ICI 46, 474 in the ovariectomized mouse.

Subcutaneous administration of ICI 46,474 (3 mg) to ovariectomized mice was found to produce vaginal refractoriness to subcutaneously administered oestradiol for up to 6 weeks. Tritiated oestradiol-17 beta accumulated in the uterus and vagina of the ovariectomized mouse, with maximum accumulation at 3 to 4 hr. This property of the target tissues was used to investigate the binding of tritiated oestradiol after the administration of 3 mg ICI 46,474 to ovariectomized mice. Radioactivity in the vagina was found to be comparable to control values 6 weeks after ICI 46,474 administration; uterine levels of radioactivity returned to control values by 10 weeks. Administration of ICI 46,474 had an oestrogenic effect upon the mouse uterus whereas the vagina appeared to be initially stimulated and was then unable to respond to or to bind oestradiol.     

Ectopic fetuses in two cottontail rabbits.

Mummified fetuses were discovered in the abdominal cavities of two cottontail rabbits (Sylvilagus floridanus) collected during separate years from the same geographical location in Virginia. One of these rabbits had a patent opening through the vaginal wall to the abdominal cavity. The uterus and vagina of the second rabbit appeared normal.     

A recessive mutation causing imperforate vagina in mice

A recessive mutation (ipv) causing imperforate vagina was discovered in a line of mice selected for low lean tissue mass as a proportion of body weight. Two full sisters were found to have marked swelling of the perineum and complete closure of the vagina. Crosses of heterozygotes identified by progeny testing produced a female progeny ratio not different from the 3 normal: 1 affected (chi 2 = 0.695; p less than .3) expected on the basis of a recessive allele at a single autosomal locus. As a consequence of the imperforate vagina, the uterus and vagina were greatly distended by fluid. The uterus of affected females displayed a swollen uterine lumen and thin endometrial stroma and muscularis. Ovarian tissue of affected females was similar to that of normal mice, and affected females produced ova that were normal in appearance. The mutation causing an imperforate vagina may present a useful model for studying the basis of abnormal vaginal development in other species and increasing the understanding of normal vaginal development in the mouse.     

The effects of light deprivation or blindness on the female genital tract of gerbils (Mariones hurrianae Jerdon)

Total absence of light or blindness results in atretic changes in the large ovarian follicles. It also caused stromal edema of the uterus and interrupted the estrous cycle. The cells found in the vaginal smear appeared to be that of diestrous. Light deprivation inhibits the synthesis of RNA and protein of the uterus and vagina. Light deprivation of blindness also results in the reduction of the uterine weight and its glycogen content. Antiestrogenic action of light deprivation or removal of the eyes was reflected in a decreased concentration of RNA, protein, sialic acid and glycogen in the uterus and vagina.     

Genital tract pressures in mares. I. Normal pressures and the effect of physiological events

A computerised system involving electronic catheter-tipped transducers was used to measure pressures developed within the vagina and uterus of mares. Larger mares tended to have lower intravaginal pressure than ponies. Insertion of an arm into the vagina to place the catheters caused a rise in intravaginal pressure. Pressure in the uterus was usually higher than that in the vagina. Both vaginal and uterine pressures were increased by urination, snorting, whinnying, stretching and respiration - the latter effect was most noticeable in larger mares. Vaginal pressure was also influenced by peristalsis in the rectum, defaecation, the passage of flatus and the stance of the mare.     

The oestrus cycle of the Senegal bush baby (Galago senegalensis senegalensis) in the Sudan

Structural changes in the overies, uterus and vagina of the Senegal galago ( Galago senegalensis senegalensis ) have been observed at several stages of the oestrus cycle in both wild and captive animals. These changes have been correlated with the periodic opening and closing of the vaginal orifice and changes in vaginal cytology. The general pattern of these structural changes was similar to that seen in other mammals but showed the following special features: periodic opening and closing of the vaginal orifice; a prolonged post-ovulatory invasion of the uterus and vagina by large numbers of eosinophil leucocytes; an unusually long life of the corpus luteum of the nonpregnant cycle. Although this animal did not menstruate its endometrium appeared to have to dual arterial supply like that seen in those higher primates that do menstruate. The coiled, elastic endometrial arteries formed a vascular adaptation to permit rapid dilatation of the uterus during early pregnancy. The urethra perforated the whole length of the long and peniform clitoris and this was associated with the periodic opening and closing of the vaginal orifice. These features made sexing very difficult. The observed time of occurrence of oestrus, together with field data on pregnancy stages and times of birth, indicated the probable occurrence of two breeding seasons in the year separated by long periods of anoestrus. Twinning was found to be uncommon.     

Mayer-Rokitansky-Kuster-Hauser syndrome type II: A rare case

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a malformation complex comprising absent vagina and absent or rudimentary uterus. MRKH syndrome may be attributed to an initial affection of the intermediate mesoderm consequently leading (by the end of the 4^th week of fetal life) to an alteration of the blastema of the cervicothoracicsomites and the pronephricducts. These latter subsequently induce the differentiation of the mesonephric and then the Wolffian and Mullerian ducts. There are very sparse such cases reported. We present a case of type II MRKH or Mullerian renal cervical somite association (i.e., Mullerian duct aplasia, renal dysplasia, and cervical somite anomalies).     

The structure of oestrogen sensitized rat vagina after exposure to steroids as studied in transplants

Summary Grafts from the vagina and the uterus were transplanted to the anterior chamber of the eye together with crystals of different steroids to investigate whether either the grafted vagina or uterus could be used as indicator of locally produced gestagens.Autologous vaginal and uterine tissues were transplanted into the anterior chamber of the eyes of 199 adult spayed female rats. Crystals of various steroids were placed near to the transplant of the right eye to investigate the local reaction. The steroids used were oestradiol-17, androst-4-ene-317 dione, testosterone, testosterone acetate, progesterone and 3-hydroxypregn-5-en-20-one. The transplant in the left eye served as a control for general reactions. Most of the animals were injected with oestradiol benzoate in order to sensitize the vagina and uterus.The daily injections with 0.1 g oestradiol benzoate produced a typical oestrous picture with a cornified epithelium both in the vagina in situ and in the grafts. The oestrous reaction increased when oestradiol crystals were implanted or when higher doses of oestradiol benzoate were injected.When testosterone or testosterone acetate was implanted in the eye the epithelium of the vaginal transplant was thinner than when only oestrogen had been given.When androsteredione crystals were used, the epithelium of the transplanted vagina was either a rather thick, non-cornified epithelium or a stratified squamous epithelium. In both epithelia mucus could be found in the cells in the upper-most layers.Implantation of progesterone changed the oestrous picture. The epithelium consisted of only 2–3 layers of cells. The upper-most layer or layers presented small to large swollen columnar mucin cells.When pregnenolone crystals were used, the grafted vagina reacted as in the progesterone series though more weakly.The uterus was not suitable for transplantation as it mostly changed into a cystic undifferentiated structure.The vagina in situ and the vaginal graft in the left eye which was not supplied with a steroid showed no characteristics that were marked and constant for any of the steroids except for the oestrogen.In the uterus in situ the gestagens, especially progesterone, caused a stimulation of the stromal cells. Their nuclei became vesicular and showed fine chromatin particles.The investigation was supported by grants from the Medical Faculty of Lund and The Royal Physiographic Society of Lund.     

Morphological and biochemical alterations in reproductive tracts of neonatal female mice treated with the pesticide methoxychlor

Effects of estradiol-17 beta and the estrogenicity of different doses of the technical grade pesticide methoxychlor were compared in the vagina, uterus, and oviducts of neonatal mice. Beginning within 24 h of birth, neonates received 10 daily i.p. injections of sesame oil vehicle, 10.0 micrograms estradiol, or 0.05, 0.1, 0.5, or 1.0 mg methoxychlor. Estradiol injections induced precocious vaginal opening, complete vaginal cornification, and increased total reproductive tract weight and its DNA content. In comparison to the controls, the three highest methoxychlor doses also significantly increased the weights of the reproductive tracts and stimulated their development. The two highest doses (0.5 and 1.0 mg) also induced precocious vaginal opening and complete vaginal cornification. In addition, the same two doses produced atypical cells in the uterus and oviducts that may be indicative of early dysplasia; similar atypia were not recorded following estradiol treatments. Total DNA content in various reproductive organs increased with increased methoxychlor dosages. Dose-response changes were observed in the oviduct and uterus but not vagina. In summary, methoxychlor stimulated the development of neonatal female reproductive tracts, even at concentrations not previously reported to be biologically active. Furthermore, the higher doses induced abnormalities that were not seen following estradiol treatment; these abnormalities may represent precursors of pathological changes.     

Action of an antiestrogen agent, tamoxifen on the uterus and vagina of the ovariectomized rat]

Tamoxifen has more or less strong estrogen influence according to the targets : a light one on the uterus (1 mg being much less strong than 0.25 microgram of estradiol), a dynamic one on the vagina (50 microgram of tamoxifen make the vagina open in as short a time as 0.25 microgram of estradiol do but the keratinisation is still not completed even with 1 mg of tamoxifen). We can still see this influence four days after the end of the treatment. This influence is weak on the uterus until the 11 th day and it is much stronger on the vagina until about the 8 th day. Tamoxifen has an antiestrogenic action when opposed to 20 microgram of estradiol : this action is limited as soon as you give a dosis of 50 microgram on the uterus and it is nearly total with a dose of 1 mg ; we can notice it on the vaginal only from 200 microgram on.     

Role of fluid from seminal vesicles and coagulating glands in sperm transport into the uterus and fertility in rats.

The relationship between the quantity of seminal vesicle secretion in the ejaculate, the percentage of spermatozoa reaching the uterus and fertility was studied in rats. Different portions of seminal vesicles were removed from male rats; 15 min after coitus (day 0), the numbers of spermatozoa in the uterus and vagina were counted and the vaginal plug characteristics were noted. Fertility was evaluated by the number of fetuses on day 14. A gradual decrease in the percentage of spermatozoa in the uterus was positively related to the reduction in seminal vesicle secretion, estimated by plug weight. This decline was not caused by a delay in sperm transport to the uterine lumen and the results suggested that the spermatozoa that fail to enter the uterus in the first minutes after coitus never enter. The vaginal plug weight, which is related to the seminal vesicle weight, and the position of the plug, which must be firmly lodged into the cervical opening, seem to be the most important conditions for promoting the rapid passage of spermatozoa into the uterus. When the seminal vesicles were partially removed, the plug was not tightly lodged and formed a 'cup' filled with spermatozoa. The number of fetuses did not show a close correlation with the quantity of seminal vesicle secretion. Studies of males in which the seminal vesicles had been removed indicated that a normal number of fetuses can be obtained despite low numbers of spermatozoa reaching the uterus. Ablation of the coagulating glands showed that, when there is no vaginal plug, no spermatozoa reach the uterus and fertility is suppressed. Nevertheless, the complete removal of coagulating glands is difficult; when small portions of these glands remain, the vaginal plug is formed and then fertility is achieved.     

腹腔镜辅助下阴式子宫切除术与阴式子宫全切除术治疗子宫良性病变的临床比较

目的:探究阴式子宫全切除术与腹腔镜辅助下阴式子宫切除术治疗子宫良性病变的临床效果。方法:选择2011年10月~2013年9月我院收治的子宫良性病变的患者120例,其中行腹腔镜辅助下阴式子宫切除术80例(研究组)和行阴式子全宫切除术40例(对照组),观察并分析两组的临床指标及手术并发症。结果:研究组住院费用明显高于对照组(P0.05),手术时间、术中出血量及住院时间均低于对照组(P0.05);研究组无邻近脏器损伤,对照组输尿管损伤2例(5.00%),研究组患者出现手术损伤率明显低于对照组,差异存在统计学差异(x2=3.968,P=0.046);对两组患者术后随访1年,两组患者均无出现再手术情况;两组患者术后阴道残端均愈合较好,未出现阴道残端漏,患者无大小便困难及其他不适。结论:腹腔镜辅助下阴式子宫切除术治疗子宫良性病变疗效优于阴式子宫全切术,其手术时间、术中出血量及住院时间均较低,创伤小,更有利于患者恢复健康,在临床上值得应用推广。     

3D finite element modeling of pelvic organ prolapse

Objectives: The purpose of this study is to develop a validated 3D finite element model of the pelvic floor system which can offer insights into the mechanics of anterior vaginal wall prolapse and have the ability to assess biomedical device treatment methods. The finite element results should accurately mimic the clinical findings of prolapse due to intra-abdominal pressure (IAP) and soft tissues impairment conditions. Methods: A 3D model of pelvic system was created in Creo Parametric 2.0 based on MRI Images, which included uterus, cervix, vagina, cardinal ligaments, uterosacral ligaments, and a simplified levator plate and rectum. The geometrical model was imported into ANSYS Workbench 14.5. Mechanical properties of soft tissues were based on experimental data of tensile test results from current literature. Studies were conducted for IAP loadings on the vaginal wall and uterus, increasing from lowest to extreme values. Results: Anterior vaginal wall collapse occurred at an IAP value corresponding to maximal valsalva and showed similar collapsed shape as clinical findings. Prolapse conditions exhibited high sensitivity to vaginal wall stiffness, whereas healthy tissues was found to support the vagina against prolapse. Ligament impairment was found to have only a secondary effect on prolapse.     

Report of a case of true hermaphroditism with karyotype 45,X/46,XX/46,X,mar/47,XX,mar

The case of a 24-year-old man with hypoplastic external genitalia, lack of the right scrotal testis and gynaecomastia has been described. In the intermitotic cells the cytogenetic investigations revealed the presence of the X body and the absence of the Y body. A 45,X/46,XX/46,X,mar/47,XX,mar karyotype could be established. On laparotomy a rudimentary ovary, uterus and vagina were detected on the right side of the abdominal cavity.     

Anterior vaginal and intrauterine pressures in mares

Resting pressure in the anterior vagina and uterus was measured monthly in eight mares for 5 mo. During this time, four of the mares maintained their body weight and four lost weight. Mean anterior vaginal pressure was -11.9 mmHg, and intrauterine pressure was -5.3 mmHg; the latter was positively correlated to body weight and weight/height ratio. Anterior vaginal pressure and uterine pressure were also positively correlated. Allowing air into the anterior vagina raised this pressure to -4.0 mmHg, i.e. higher than uterine pressure. There was a tendency for genital tract pressures to be lower in anoestrous mares than those which remained cyclic. Some physiological events caused marked increases in genital pressures.     

The germ layer origin of mouse vaginal epithelium restricts its responsiveness to mesenchymal inductors: uterine induction

The epithelium of the mammalian vagina arises from two distinct germ layers, endoderm from the urogenital sinus and mesoderm from the lower fused Müllerian ducts. While previously it has been reported that neonatal vaginal epithelium can be induced to differentiate as uterus, which normally develops from the middle portion of the Müllerian ducts, it has not been determined whether this ability is shared by both mesoderm- and endoderm-derived vaginal epithelia. To test if germ layer origin influences the ability of vaginal epithelium to undergo uterine differentiation, we have isolated sinus-derived and Müllerian-derived vaginal epithelia from newborn mice, combined them with uterine mesenchyme, and grown them for 4 weeks in female mice. Mesoderm-derived Müllerian vaginal epithelium in combination with uterine mesenchyme formed the simple columnar epithelium typical of uterus. Similar results were obtained with neonatal cervical epithelium, another mesodermal Müllerian duct derivative. On the other hand, sinus vaginal epithelium combined with uterine mesenchyme formed small cysts lined by a stratified squamous vaginal-like epithelium. This epithelium never showed evidence of cycling between the cornified and mucified states as is typically seen in vaginal epithelium combined with vaginal stroma. These results indicate that the ability of epithelium to form uterus is limited to mesoderm-derived epithelia and suggest that endoderm-derived sinus vaginal epithelium cannot undergo the typical differentiative modifications in response to the hormonal fluctuations of the estrous cycle when associated with uterine stroma.