Oviductal Fimbriae Research Articles

Morphology, Glycan Pattern, Heat Shock Proteins, and Sex Steroid Receptors Expression in the Tubal Fimbria Epithelium of the Baboon Papio hamadryas during the Menstrual Cycle.

The oviductal fimbria is the first extraovarian anatomical structure that the cumulus-oocyte complex (COC) encounters, and is sensitive to sex hormone changes. The morphology, glycan pattern, expression of heat shock proteins (HSPs), estradiol receptor (ER), and progesterone receptor (PR) were investigated in the oviductal fimbria epithelium of the baboon (Papio hamadryas) during the menstrual cycle. The morphology was investigated by light and scanning electron microscopy; the glycopattern was characterized using conventional and lectin histochemistry; HSPs (60, -70, -90), ER, and PR were localized immunohistochemically. Well-differentiated ciliated and nonciliated cells were present only during the preovulatory phase. The nonciliated cells contained small apical protrusions and thin microvilli. During the preovulatory phase (1) the luminal surface of the fimbria displayed acidic glycans, complex N-glycans containing fucose, and oligolactosamine residues; (2) nonciliated cells expressed HSP60 and HSP90 in the apical blebs, HSP70 in the nucleus and cytoplasm, as well as nuclear ERα and PR; (3) ciliated cells showed HSP70 in the nucleus, cytoplasm, and cilia that also expressed HSP90 and PR. These results are related to the function of the fimbria where the early COC-oviduct crosstalk occurs and may represent a benchmark for translational studies of other primates.

Incidence of malignant transformation in the oviductal fimbria in laying hens, a preclinical model of spontaneous ovarian cancer.

Ovarian high grade serous carcinoma (HGSC) is a lethal form of ovarian cancer (OVCA). In most cases it is detected at late stages as the symptoms are non-specific during early stages. Emerging information suggests that the oviductal fimbria is a site of origin of ovarian HGSC. Currently available tests cannot detect ovarian HGSC at early stage. The lack of a preclinical model with oviductal fimbria that develops spontaneous ovarian HGSC is a significant barrier to developing an early detection test for this disease. The goal of this study was to examine if the oviductal fimbria in hens is a site of origin of HGSC and whether it expresses several putative markers expressed in ovarian HGSC in patients. A total of 135 laying hens (4 years old) were selected from a flock using transvaginal ultrasound (TVUS) imaging, followed by euthanasia and gross examination for the presence of solid masses and ascites. Histological types of carcinomas were determined by hematoxylin and eosin staining. Expression of WT-1, mutant p53, CA-125, PAX2 and Ki67 in normal or malignant fimbriae or ovaries were examined using immunohistochemistry, immunoblotting and gene expression assays. This study detected tumors in oviductal fimbriae in hens and routine staining revealed ovarian HGSC-like microscopic features in these tumors. These tumors showed similarities to ovarian HGSC in patients in expressing several markers. Compared with normal fimbriae, intensities of expression of WT-1, mutant p53, CA-125, and Ki67 were significantly (P<0.05) higher in fimbrial tumors. In contrast, expression of PAX2 decreased gradually as the tumor progressed to late stages. The patterns of expression of these markers were similar to those in ovarian HGSC patients. Thus, tumors of the oviductal fimbria in hens may offer a preclinical model to study different aspects of spontaneous ovarian HGSC in women including its early detection.

The Stem-Cell Profile of Ovarian Surface Epithelium is Reproduced in the Oviductal Fimbriae, with Increased Stem-Cell Marker Density in Distal Parts of the Fimbriae

High-grade serous ovarian carcinomas are the most common and most lethal ovarian cancers, but their histologic origin is still controversial. Current evidence suggests that they may originate in the ovarian surface epithelium (OSE) and/or epithelium of oviductal fimbriae (FE). To further investigate this question we compared the stem-cell profiles of these epithelia. Formalin-fixed sections of normal FE (N=21) and ovaries (N=21) were stained immunohistochemically for the stem-cell markers NANOG, SFRP1, LHX9, ALDH1A1, and ALDH1A2. All markers were detected in both OSE and FE. A total of 75% to 100% of surface OSE expressed all markers except ALDH1A1, which occurred in about 25% of cells. Among epithelial inclusion cysts with flat-to-cuboidal epithelium, resembling OSE, ALDH1A1 was significantly increased, whereas SFRP1 was reduced compared with surface OSE, suggesting an increased trend towards malignant transformation. Similarly, among cysts lined by columnar cells resembling FE, SFRP1 expression was low, whereas ALDH1A1 approached 100% of the cysts. FE exhibited considerable variation between and within specimens. In about half of the samples, SFRP1 and NANOG were detected in ≤25% FE. The most widespread markers were ALDH1A1 and ALDH1A2. The highest proportion of all markers occurred in the distal parts of the FE, the site of the putative ovarian cancer precursors. Marker expression in tubal ampullae was low or absent except for ALDH1A1 and ALDH1A2. The results provide an explanation for the characteristic distal location of fimbrial high-grade serous ovarian carcinoma precursor lesions, and indicate that both OSE and FE have the capacity to undergo neoplastic transformation.

The origin of ovarian cancers - hypotheses and controversies

Ovarian cancer is the prime cause of death from gynecological malignancies in the Western world. In spite of its importance, it is poorly understood and its prognosis remains poor. The most common and lethal of all ovarian cancer subtypes are the high grade serous ovarian carcinomas (HGSOCs). A major problem in their clinical management is the current uncertainty about their cell type of origin, which limits means of early detection and prevention. It has not been resolved whether all HGSOCs originate in oviductal fimbriae or in ovarian surface epithelium (OSE). This review summarises evidence for these two hypotheses and considers the alternative possibility that HGSOCs may arise at both sites. This concept is based on the common embryonic origin of OSE and fimbriae in the coelomic epithelium and evidence of overlapping differentiation between these epithelia in the adult, which suggests incomplete commitment and pleuripotentiality. This hypothesis would account for OSE and fimbriae giving rise to identical carcinomas, and for their susceptibility to neoplastic transformation that is absent in the adjacent extraovarian serosa and oviductal ampulla.

The Origin of Ovarian Carcinomas

It is currently a controversial issue whether epithelial ovarian cancers arise in the ovarian surface epithelium (OSE) or the fimbrial epithelium of the oviduct. The hypothesis presented here aims to reconcile these 2 views and provides a possible explanation for 2 questions arising: first, why tumors originating in the fimbriae and OSE, which are parts of different organs, express common features; second, why these epithelia are prone to neoplastic transformation whereas the remaining oviduct and the extraovarian mesothelium are not. We hypothesize that these questions relate to the common origin of the OSE and fimbriae in that region of the embryonic coelomic epithelium, which will eventually link the extraovarian mesothelium to the epithelium of the oviductal ampulla. OSE and fimbriae become separated during embryonic development but, like other transitional, interepithelial junctions in adults, this region might remain incompletely committed and thus prone to neoplastic progression. To define differentiation at the OSE-tubal junction, salpingo-oophorectomy specimens were stained immunohistochemically for mesenchymal differentiation markers of OSE and for epithelial markers and Pax8, characterizing oviductal fimbriae and ampullae. OSE and ampullae were distinctly different, but there was no sharp boundary between OSE and fimbriae. Rather, both mesenchymal and epithelial markers overlapped, and Pax8 and fimbrial epithelial markers diminished distally, near the OSE. The results support the hypothesis that the OSE and fimbriae are parts of a transitional epithelium of common origin rather than 2 independent sources of ovarian cancer, and suggest that their immature, incompletely determined phenotype contributes to their propensity to neoplastic transformation.

Techniques for the Insemination of Low Doses of Stallion Sperm

In the last decade, there has been a significant increase in the quality and commercial use of frozen equine semen. The emergence of new reproductive technologies, coupled with the high prices for an insemination dose from some stallions, the increasing costs of import and export and the marketing policies of stallion agents or owners in the sport horse industry has stimulated the fractionation of doses for insemination. Consequently, the sperm number and the volume of an insemination dose are significantly reduced. To deliver lower doses of sperm in lower volumes compared to the standard dose, two techniques are used in clinical practice. Semen can be delivered hysteroscopically (HI) or by rectally guiding a flexible pipette to the tip of the desired uterine horn (RI). Both techniques have been described with good success and have triggered an incentive to further reduce the number of spermatozoa without having a negative effect on fertility. This article will review the expected success of both techniques in clinical settings and will highlight their advantages and disadvantages both for the mare and stallion. In addition, some of the implications of reducing sperm numbers on the industry will be discussed. From the available information, it is evident that lower sperm numbers deposited by RI or HI to deliver the inseminate can result in acceptable pregnancy rates with fresh or frozen semen in commercial settings. These methods of insemination could have major implications in the implementation and commercialization of new and emerging technologies in the equine industry.

026. The cumulus matrix in ovulation: inert packaging or active delivery vehicle for the oocyte?

Preovulatory follicles respond to the LH-surge with a cascade of molecular events. The ovulatory signal initially impinges on the mural granulosa layers triggering rapid tissue morphogenesis and ultimately terminal differentiation of these cells. Mural granulosa cells transiently produce a suite of transcriptional regulators, EGF-like ligands as well the extracellular matrix (ECM) proteoglycan, versican and the protease ADAMTS-1. These act in concert with permissive oocyte signals to induce and organise a complex hyaluronan (HA) rich ECM surrounding the cumulus cells and oocyte. This expanded cumulus matrix is analogous in composition to an extensive form of pericellular matrices actively associated with cell migration. During ovulation the cumulus matrix becomes anti-adhesive to the intra-follicular environment but is strongly pro-adhesive for the oviductal fimbria. When the follicle apex is perforated the COC is released binds to the fimbria and transports into the oviduct where fertilisation occurs. Success of ovulation and fertilisation is sensitive to the appropriate production and assembly of cumulus matrix components that are in turn dependent on an appropriate balance of oocyte and granulosa derived signals. Production of these cumulus matrix components is thus a potential checkpoint that assures ovulation of competent oocytes. The HA matrix is cross-linked by organiser molecules and also is enriched in proteases ADAMTS-1, 4, 5. Although these have potentially redundant functionality, ADAMTS-1 null female mice are profoundly sub-fertile and have reduced ovulation rate. Specific components of the cumulus matrix are disorganised in ADAMTS-1 null mice and cleavage of versican in these cumulus complexes is reduced. Thus ADAMTS-1 and versican have unique roles in normal cumulus matrix expansion that is important for ovulation. Altered interaction of the cumulus complex with neighbouring tissues alters transport through the oviduct, while abnormal persistence of COC matrix structure after ovulation is also likely to impair sperm interaction and penetration. Evidence thus indicates that the expanded cumulus matrix plays several active roles in oocyte release, transport and sperm interaction.

Investigation of ovum transport in the oviduct: the dynamics of oviductal fluids in domestic rabbits.

Ova are captured by the oviductal fimbria and rapidly transported to the ampullary-isthmic junction of the fallopian tube. Fertilized ova and oviductal fluids are then carried medially in the fallopian tube, while undergoing maturation in preparation for entering the uterine cavity, where nidation and further development take place. This movement of oviductal fluids was visualized in a rabbit model with human chorionic gonadotropin-induced ovulation, by injection of a contrast medium into the ampulla region of the oviduct. In the ampulla, the opaque medium was observed to oscillate at 0-85.4 mm/s. This medial transport of the fluid towards the uterus decreased to 0-9.6 mm/s in the isthmic portion of the tube. This decrease substantiates previous findings that the transport of material in the isthmic portion of the oviduct is more strongly under the control of ciliary action than under peristaltic activity.

Endocrine and paracrine regulation of cumulus expansion.

In a Graafian follicle, granulosa cells are classified into two principal cell subpopulations: cumulus cells, which are closely associated with the oocyte to form the cumulus cell-oocyte complex (COC), and mural granulosa cells, which are organised as a stratified epithelium at the periphery of the follicle. Following the preovulatory gonadotropin surge, cumulus cells lose contact with mural granulosa cells and start to synthesise and secrete a large amount of hyaluronan (HA), a glycosaminoglycan with high molecular weight and large hydrodynamic domains (Salustriet al., 1992). Proteins derived from serum (Chenet al., 1992, 1994) and synthesised by cumulus cells (Camaioniet al., 1993, 1996) organise the strands of HA into an intercellular elastic network that traps the cumulus cells and the oocyte in a unit which can not be mechanically dissociated – a process also referred to as cumulus expansion. At ovulation, the expanded COC is released through the ruptured follicle wall and transferred to the oviduct. The matrix in the expanded COC facilitates its extrusion from the follicle and its capture by oviductal fimbria, and provides, together with the cumulus cells, a suitable microenvironment for sperm penetration and fertilisation (for references see Salustriet al., 1993).

An Estrogen-Dependent Glycoprotein is Synthesized and Released from the Oviduct in a Temporal- and Region-Specific Manner during Early Pregnancy in the Ewe1

Administration of estradiol-17 beta (E) to ovariectomized (ovx) sheep results in the synthesis and release of an M(r) 90,000-92,000 glycoprotein into the oviductal lumen and into culture medium of ampullar explants (Biol Reprod 1992; 47:889-902). The objective of this study was to determine when and from what region of the oviduct the M(r) 90,000-92,000 glycoprotein is synthesized and released during early pregnancy. Estrous ewes were bred to intact rams of known fertility, and oviducts were obtained at estrus (Day 0) and at Days 1.5, 2, 3, 4, 6, and 16 of pregnancy. Pregnancy was verified by the presence of a fertilized egg or developing conceptus and a functional corpus luteum. Oviductal secretions were collected by flushing oviducts with saline and by explant culture. The oviductal fimbria, ampulla, and isthmus were individually cultured (24 h) in the presence of 3H-leucine (3H-leu) or 3H-glucosamine (3H-glcN). The presence of the M(r) 90,000-92,000 glycoprotein in oviductal flushings and culture medium was determined by fluorography and Western blotting. The M(r) 90,000-92,000 protein was present in SDS gels and blots of oviductal flushings from animals through Days 4-6 of pregnancy, but not in flushings from Day 16 pregnant animals or from ovx, untreated animals. This protein was present in 3H-leu- and 3H-glcN-labeled culture medium of the oviductal ampulla (Days 0, 1.5, 2, 3, 4, 6, and 16) and fimbria (Days 0, 1.5, 2, 3, and 4) during early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Peritoneal Dialysis Catheter Outflow Obstruction Due to Oviductal Fimbriae: A Case Report

Outflow obstruction is a common cause of peritoneal dialysis catheter malfunction. We report an unusual case of outflow obstruction caused by oviductal fimbriae. Mini-laparatomy and repositioning of the catheter without excising the fallopian tube resulted in good outcome.

A factor inhibiting ovum capture by the oviductal fimbriae present in endometriosis peritoneal fluid

The cumulus-fimbria interaction was investigated in vitro with endometriosis peritoneal fluid (PF). On the oviductal fimbria of the golden hamster, incubated with endometriosis and nonendometriosis PF and culture medium 199 contained 4% bovine serum albumin (control), was placed the mouse oocyte-cumulus complex at 5-minute intervals for 60 to 70 minutes. Incubation periods until the loss of fimbrial capability of ovum capture (ovum capturability disappearance time [OCDT] ) were 23.3 +/- 2.7 (standard error of the mean), 51.7 +/- 2.9, and 61.3 +/- 0.9 minutes with endometriosis, nonendometriosis PF, and control, respectively. OCDT was significantly decreased with cell-free and ultrafiltrated endometriosis PF containing a molecular size greater than 100,000 (26.0 +/- 2.8 and 26.1 +/- 2.5 minutes, respectively). A factor inhibiting fimbrial capability of ovum capture is present in endometriosis PF.

Parameters influencing ovum pickup by oviductal fimbria in the golden hamster

AbstractThe process whereby hamster oviductal fimbria transport ova to the ampulla was investigated in vitro and in vivo with the intent of determining whether cumulus‐free ova were transported and resolving some of the parameters involved in cumulus‐isolated from ovaries could not be picked up until 16–17 h before it would be ovulated. This was apparently related to the time at which the cumulus matrix begins to expand. The fimbria were not species‐specific, as they readily picked up rat, mouse, and rabbit ovulated cumul, but they were partially tissue‐specific as they would only pick up tissues such as the vitreous humor and loose connective tissue, which contain considerable extracellular glycosaminoglycan. Interaction of cumulus and fimbria could be prevented b treating either structure with polycatinic macromolecules such as poly‐l‐lysine, cationic ferritin, and protamine. Treatment of fimbria with proteolytic enzymes or hyaluronidase did not prevent pickup, but neuraminidase did. The only “artificial cumulus” the fimbria would pick up was chicken egg‐white. Cumulus‐free ova were not picked up in vitro, but part of them placed into the ovarian bursa were transported to the ampulla in vivo. Coating the ova with chicken egg‐white allowed their pickup in vitro, but had little effect on the success of transport of ova transplanted into the ovarian bursa in vivo. The transport of ova from the ovarian bursa to the oviductal ampulla is apparently a rather complex process involving interaction of some component of the cilia surfaces with the cumulus as well as other factors not necessarily related to this interaction.