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Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium.

Ovarian organogenesis requires the coordinated specification of supporting and steroidogenic cell lineages from multipotent coelomic epithelium (CE) progenitors. A longstanding question is whether the CE contains transcriptionally distinct, spatially organized progenitor subpopulations with predetermined lineage biases, or whether specification into supporting and steroidogenic lineages occurs only after delamination and integration into the bipotential gonad. The developmental origins of granulosa cells and the emergence of ovarian steroidogenic/stromal progenitors (SPs) also remain poorly defined. Here, we show that CE cells covering the fetal mouse ovary are transcriptionally heterogeneous and spatially organized into subdomains already primed toward supporting or steroidogenic fates. CE priming is dynamic, with transient coexistence of supporting- and steroidogenic-biased CE progenitors before resolving into a predominantly supporting-biased CE. Local delamination of these primed cells seeds intragonadal niches where pre-granulosa cells and SPs mirror the spatio-temporal arrangements of CE-primed progenitors. We further demonstrate a dual origin for the supporting lineage, with granulosa cells deriving from both the CE and supporting-like cells (SLCs). In parallel, we show that SPs arise from steroidogenic-primed CE cells, expand to represent 52% of ovarian somatic cells at birth, persist into adulthood and contribute to both theca and steroidogenic stromal cells. Together, these findings reveal transcriptionally and spatially distinct CE subpopulations that shape somatic lineage emergence with important implications for ovarian pathophysiology.

Ovarian development

Ovarian cystomas and ovulation, a histogenetic concept.

The current histologic classification of tumors of the ovary and testis is reviewed, and their relative frequency is illustrated by notifications to the Swedish Cancer Registry from 1959 to 1965. By far the most common neoplasms were epithelial tumors of the ovary (i.e., cystomas). These do not occur in the testis. Cystomas are believed to originate from the surface epithelium (coelomic epithelium, mesothelium) of the ovary, but there is no generally accepted explanation of how the epithelial cells enter the ovary. Based on the absence of cystomas in the testis, the suggestion is advanced that epithelial inclusions may arise during the reparative period following ovulation. The implications of this concept for the histogenesis of cystomas are discussed.

Cystadenoma

[Epithelial differentiation of rudimentary gonads of human embryos].

Changes in coelomic epihtelium of the germinal gonads in human embryos at the age of 28-35 days of intrauterine development were studied after fixation in Carnoy's fluid, in Shabadash's fluid, in 12% neutral formalin. Paraffin sections were stained with hematoxylin, with ferric hematoxylin after Heidenhain. Fibrils of the basal membrane were detected by silver impregnation after Karupu. PAS-reaction after McManus with additional staining by hamatoxylin and light green and the reaction with bromfenol blue after Michel-Kalvoux to reveal total proteins were applied. Since gonad formation, its coelomic epithelium resembles false pseudostratified one: the nuclei are arranged at different levels, with apical position of mitoses. The cells of the "germinal" epithelium secrete protein-polysaccharide products. The process reaches its maximum by 31-33 day of embryogenesis and coincides with the appearance of the gonads of primary sex cells in the epithelium. This secretion is probably connected with production of an "attractive factor" for gonocytes. On apical surfaces of the epithelium of the gonads, silver impregnation, PAS-reaction and reaction for total proteins reveal an edge which is probably represented by microvilli. The basal membrane of the coelomic epithelium of the gonads loses its integrity when migrating gonads penetrate into the "germinal" epithelium. Later, the integrity of the basal membrane structure is restorted. All these make it possible to consider the epithelium of the embryonal gonads as a specific, different from the other coelomic epithelium layer.

Cell Differentiation

[Coelomic gonadal epithelia during the period of human embryonic morphologic sex differentiation].

The course of divergent differentiation of coelomic epithelium in the indifferent gonad has been traced up to the stage when morphological sex signs are distinctly seen. Eleven human embryos fixed in Carnoy and Bouin's fluid have been studied from 6 to 10 weeks of gestation. Paraffin sections were stained with hematoxylin, ferric hematoxylin after Heidenhain. Basal membrane fibres were revealed by silver impregnation after Karupu. PAS-reaction after McManus and additional staining with hematoxylin and light green were applied, as well as the reaction for total proteins with bromphenol blue after Miguel--Calvo. Sex differentiation of coelomic epithelium in the gonad developing according to the male type begins a little later than in the ovary. In the epithelium of the forming testis a great amount of mitotic figures is observed that might be connected with the presence of Y-chromosome stimulating cells for extra mitotic cycles. The increasing presence of Y-chromosome stimulating cells for extra mitotic cycles. The increasing number of mitotic figures in the epithelium should be considered as a sign demonstrating that differentiation according to the male type has started. Superficial epithelium of the embryonic ovary has a peculiar false pseudostratified structure. This secures cellular reserve for the ovarian cortex formation from the external epithelium. The apical surface of the cells in the external epithelium has a border which is evidently formed by microvilli and revealed by PAS-reaction and bromphenol blue. Ovarian follicular cells and Sertoli's cells (sustentocytes) in testis have the common origin in the human fetus--from coelomic epithelium of the gonad germ.

Epithelial Cells

Ovarian differentiation in Turner's syndrome.

The authors have studied the gonadal histogenesis and the sexual chromosome influence on the gonads of 17 patients with the following complements : 45,X/46,XXqi (1 case); 45,X (4 cases); 45,X/46,XXP--(1 cases); 45,Xq-- (1 case); 45,X/46,XX (8 cases); 45,X/46,XX/46,XXqi (1case); and 45,X/46,XXqi/47,XXqiXqi (1 case). The presence of sexual differentiation structures was investigated : coelomic epithelium, stromal characteristics, follicles sexual cords, medullary tubules, rete ovarii, hilar cells, mesonephric remnants and coelomic epithelium inclusions. All gonads were constituted by rudimentary ovarian stroma with different states of hyalinization. Primordial follicles were noted in two patients with respectively 45,X/46,XX and 45,X/46,XXqi/47,XXqiXqi karyotypes, and a cystic follicle was present in one patient 45,X/46,XXp--. Sexual cords were seen in 6 patients and medullary tubules in 9. Different amounts of hilar cells were found as well. The authors conclude that in Turner's syndrome there exists an ovarian dysgenesis which is probably caused by early involution before reaching the maturation, conditioned by the genetic incapacity of the oogonia to complete the meiotic prophase.

Adolescent

The basiepithelial nerve plexus of the viscera and coelom of eleutherozoan Echinodermata.

The organisation of the basiepithelial nerve plexus in the alimentary canal of a starfish and the water vascular system of a sea-urchin is described. The plexus contains varicose aminergic neurones which terminate adjacent to the ciliated epithelial cells. It is proposed that the basiepithelial plexus innervates these cells and controls ciliary beating. The distribution of the basiepithelial plexus in various tissues described by other workers is discussed particularly in relation to whether it is the coelomic epithelium or the luminal epithelium which is innervated. It is concluded that where there is both an endothelium and a coelomic epithelium only one is innervated. The muscles, where present, of the viscera are innervated by a separate nervous system. The muscles are always on the opposite side of the non-cellular connective tissue sheath to the basiepithelial plexus.

Animals

Fine structure of the axial complex of Sphaerechinus granularis (Lam.) (Echinodermata: Echinoidea).

Three regions of the axial complex in Sphaerechinus granularis can be distinguished: 1) The axial organ which protrudes from one side of the axial sinus; the sinus septum which separates the sinus from the body cavity and encloses the stone canal; the pulsating vessel which runs along the inside of the axial organ. 2) The blindly-ending terminal sinus in which the pulsating vessel broadens out to the contractile terminal process. 3) The ampulla of the stone canal which connects the axocoel and water vascular system and which opens out through the madreporite. A single-layered, monociliated coelomic epithelium surrounds all regions of the axial complex. This epithelium contains smooth muscle cells at the contractile areas. Canaliculi, surrounded by basal lamina, are formed through infolding of epithelia; they end blindly in the fluid- and connective tissue-matrix of the inner structures. The lacunae of the dorso-ventral mesentery connect the periesophageal and the perianal haemal ring with the axial organ. The axial organ contains many coelomocytes rich in pigment and granules. These coelomocytes are separated into compartments by elastic fibres. Phagocytosis of whole cells and transformational stages of coelomocytes suggest storage and degradation functions. An excretory function via the water vascular system is also suggested.

Animals

Solitary (localized) pleural mesothelioma. A light- and electron-microscopic study.

Six solitary (localized) pleural mesotheliomas were studied by light and electron microscopy. All the lesions were benign and were composed mainly of fibrous tissue of variable cellularity with or without cystic spaces lined by round cells. The lining cells of the cysts and the adjoining round plump cells were interpreted as true neoplastic cells of the fibroblast type. Results of light- and electron-microscopic study of human mesothelial cells and fetal mesothelial cells of rats were compared. The cytoplasmic organelles of the tumor cells were generally scanty, though rough endoplasmic reticulum, sparse mitochondria, intracellular bundles of fibrils, and numerous polysomes were seen. Some tumor cells had junctional apparatus and basement membrane and showed interdigitation of the plasma membrane. These cells lined the cystic spaces irregularly and also proliferated into the surrounding fibrous tissue, where they assumed a spindle shape and resembled fibroblasts. Ultrastructurally, the tumor cells were similar to mesothelial and stromal cells of fetal rat pleura. We speculated that the solitary (localized) mesotheliomas were probably derived from coelomic epithelium and that tumor cells remained undifferentiated or revealed minimal differentiation toward mesothelial cells.

Adult

Human testicular development and the role of the mesonephros in the origin of a dual Sertoli cell system.

Some aspects of the development of the human testis (and overy) are discussed and the main theories regarding gonadal differentiation summarized. The major part of this review deals with the origin and differentiation of the three groups of somatic cellular content: Sertoli cells, Leydig cells and peritubular cells. The most important role of the mesonephros in gonadal development is described. Under the influence of the mesonephros, a second type of meiosis-inducing Sertoli cell differentiates and becomes the opponent of a meiosis-preventing type of Sertoli cell which derives from the coelomic epithelium. All somatic cells are pooled in the central gonadal blastema which is part of the medulla. They migrate via the rete blastema to the sites of their final differentiation. Included are the precursors of the Leydig cells and the peritubular cells.

Cell Differentiation

The Brenner tumor: a clinicopathologic review.

The Brenner tumor of the ovary has been the topic of voluminous clinical and pathologic literature since its original description by Macnaughton-Jones in 1898. One of the major problems confronting most investigators of this uncommon neoplasm has been the question of histogenesis. There is general agreement that the tumor is derived from surface (coelomic) epithelium, as are the serous and mucinous cystadenomas. Most Brenner tumors are asymptomatic except for some which have features suggestive of estrogen production. The major pathologic variants are the proliferating and the malignant Brenner tumors; a poor prognosis is associated with the latter neoplasm. Approximately 30% of all benign Brenner tumors have a second histologic type of tumor in the ipsilateral or contralateral ovary, a serous or mucinous cystadenoma in most cases. Brenner tumors have also been reported in the broad ligament and in the testis on rare occasions.

Adult

[Development of the seminiferious tubules and rete testis during the prenatal period of human ontogenesis].

The sources of origin and the peculiarities of formation of the seminal ducts and rete testis during the prenatal period of ontogenesis in man were studied. It has been established that the seminal duct sand the ducts of the rete testis form from the cellular cords of the coelomic epithelium and the primordial germ cells which appear simultaneously in the septum of the testis and the primordial germ cells which appear simultaneously in the septum of the testis and central part of its parenchyma in the embryos, 13.0--17.0 mm long. By plastic and graphic reconstruction, as well as by methods of subtle preparation under binocular microscope MBC-I control it was revealed that the seminal ducts anastomosed between themselves both within the limits of one and the adjacent lobules. The ducts of the rete testis do not form anastomoses, but superimpose over one another, creating an impression of a rete. Approaching the tunica albuginea they merge, continuing into the cuctuli efferentes testis.

Humans

[The first stages of the appendix development in the human embryo].

The cecoappendicular area of 14 human embryos with a length ranging from 6 to 17 mm from vertex to coccyx (28 to 48 days old; Carnegie stages 13 to 19) was studied. The appendix is not an atrophic remain of the caecum, it develops at the same time as the caecum. The first morphological anlage of the organ is observed in human embryos from 6 to 10 mm (28 to 37 days of age; Carnegie stages 13 to 16) in the form of an elevation covered with coelomic epithelium, constituted by the mesenchyme which surrounds the anlage of the caecum. In later stages, on human embryos of 11 to 16 mm (37 to 44 days of age; Carnegie stages 16 to 18), the mesoblastic anlage of the appendix is more evident, but it is not invaded by the entoblastic cells which come from the caecum on embryos of 12 to 13 mm. On embryos of about 17 mm (48 days old; Carnegie stage 19) the entoblastic anlage of the appendix has invaded the original mesoblastic anlage. The formation of the appendix by two anlage one earlier, mesoblastic, and another later, entoblastic, is similar to that of other lymphoid organs like the sack of Fabricius in birds.

Appendix

Mucinous cystadenocarcinoma of the retroperitoneum.

A case of a primary retroperitoneal mucinous cystadenocarcinoma of ovarian type found at laparotomy in the presence of two normal ovaries is described. Careful examination of the tumor showed no evidence of ovarian tissue in the wall. The appearance of this tumor could be traced from areas of benign mucinous cystadenoma, through a mucinous tumor of borderline malignancy to a highly malignant anaplastic tumor containing only occasional mucicarmine positive cells. In areas, the connective tissue of the neoplasm, resembled ovarian stroma in appearance. At autopsy, the retroperitoneum was free of neoplasm, but widespread metastases, consisting of poorly differentiated adenocarcinoma were observed. This neoplasm may have arisen from displaced coelomic epithelium or from a supernumerary ovary.

Cystadenoma

Epidermoid cysts of the ovary: a report of five cases with histogenetic considerations and ultrastructural findings.

Five cases of epidermoid cysts of the ovary are added to the two-reported in the literature. This rare lesion was uniformly an incidental finding in the study of hysterectomy specimens. Its main interest is in its histogenesis, which is suggested to involve metaplasia of the coelomic surface epithelium of the ovary. Ultrastructural evidence is one case strongly favors this possibility, thus adding another line of differentiation to those already established for the multipotent coelomic epithelium. However, some cases may be teratoid in origin, as has been suggested for the analogous lesion in the testis.

Adult

[Ovarian cancer in a monocygotic twin pair (Author's transl)].

We report on a female monocygotic twin pair, where the two women fell ill of an adenocarcinoma of the ovaries almost simultaneously. The paramesonephric epithelium of the coelom is discussed as origin for the disease. The concordance of the disease in the same environment points to the genetic factors is being more important in the development of the disease. Nevertheless a clearcut hereditary troit can not be defined at this time.

Adenocarcinoma

Ultrastructure of the benign and borderline Brenner tumours.

One benign Brenner tumour and one Brenner tumour of borderline malignancy were investigated by electron microscopy. The cells of the benign Brenner tumour nests and the cells in the borderline tumour were similar in ultrastructure. The intercellular spaces were large and reinforced by a moderate number of desmosomes. The nuclei were round or oval. The nuclear membrane was irregular in shape with deep infoldings corresponding to the characteristic nuclear groovings seen by light microscopy. Only few secreting cells could be found in the benign of Brenner tumour. The cystic cavities of the borderline Brenner tumour were lined by nonciliated secreting and ciliated nonsecreting cells. The secretory granules were PAS-positive and diastaseresistant. The granules stained homogeneously and strongly with the PASM-method at the electron microscopical level indicating the presence of 1.2-hydroxyl groups. The Brenner tumours have many similarities to the transitional epithelium and to the Muellerian-derived tubular structures. The findings support the theory that Brenner tumours are of coelomic origin and develop by direct metaplasia from the ovarian surface epithelium.

Brenner Tumor

A trypsin-like oviducal proteinase involved in Bufo arenarum fertilization.

When the jelly-less eggs removed from the most cephalic region of the oviduct (pars recta) of the toad Bufo arenarum were inseminated at a high sperm concentration, high frequencies of fertilization were obtained. On the other hand, control eggs removed from the pleuroperitoneal cavity (coelomic eggs)) were neither fertilized upon insemination under identical conditions, nor with the water extract of the jelly. Under these inseminating conditions, however, a high frequency of fertilization was obtained when coelomic eggs were preincubated in the presence of the fluid secreted by the epithelium of the pars recta or of an extract prepared from pars recta homogenate. Experimental evidence is presented showing that the component responsible for this effect acts on the vitelline envelope of the egg, increasing its susceptibility to sperm lysin. It is probable, therefore, that it induces successful fertilization of coelomic eggs by making the vitelline envelope more easily penetrable by sperm. The active factor was partially purified by Sephadex chromatography. The product obtained was of high activity and, as judged by its inhibition with soybean trypsin inhibitor and lima-bean trypsin inhibitor, it is likely to be a trypsin-like enzyme. The molecular weight of the factor was estimated to be 47000 by Sephadex chromatography. Secretion of the pars recta factor is hypophysis-dependent and its activity is not influenced by pH within the range testes (6.0--8.4).

Animals

An ultrastructural study of the dermal papulae of the starfish, Asterias rubens, with special reference to innervation of the muscles.

The ultrastructure of the dermal papulae of a starfish (Asterias rubens) is consistent with a respiratory function. The present study has shown no regions specialized for excretory mechanisms. The papulae consist of an outer ectodermal epithelium of sensory, support and gland cells and a small basiepithelial nerve plexus. A true basement membrane lies underneath the epithelium and regularly arranged longitudinal muscle bundles lie within the connective tissue. The coelomic cavity of the papulae is lined with ciliated endothelial cells, which overlie an irregular layer of circular muscles. A system of canals that are not lined by cells occurs at the base of the papulae with the circular muscles. The longitudinal and circular muscles show a different gross morphological arrangement and innervation. This paper proposes that there are "skeletal" and "visceral" types of smooth muscle in echinoderms and discusses this proposal at length.

Animals