Characterization of the human fetal gonad and reproductive tract by single-cell transcriptomics.

During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular composition of male and female human fetal gonads is well described, that of the adjacent developing reproductive tract remains poorly characterized. Here, we performed single-cell transcriptomics on male and female human fetal gonads together with the adjacent developing reproductive tract from first and second trimesters, highlighting the morphological and molecular changes during sex differentiation. We validated different cell populations of the developing reproductive tract and gonads and compared the molecular signatures between the first and second trimesters, as well as between sexes, to identify conserved and sex-specific features. Together, our study provides insights into human fetal sex-specific gonadogenesis and development of the reproductive tract beyond the gonads.

Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary.

The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray's Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

Transcriptome analysis of the mouse fetal and adult rete ovarii and surrounding tissues.

The rete ovarii (RO) is an epithelial structure that arises during fetal development in close proximity to the ovary and persists throughout adulthood in mice. However, the functional significance of the RO remains elusive, and it has been absent from recent discussions of female reproductive anatomy. The RO comprises three distinct regions: the intraovarian rete (IOR) within the ovary, the extraovarian rete (EOR) in the periovarian tissue, and the connecting rete (CR) linking the EOR and IOR. We hypothesize that the RO plays a pivotal role in maintaining ovarian homeostasis and responding to physiological changes. To uncover the nature and function of RO cells, we conducted transcriptome analysis, encompassing bulk, single-cell, and nucleus-level sequencing of both fetal and adult RO tissues using the Pax8-rtTA; Tre-H2B-GFP mouse line, where all RO regions express nuclear GFP. This study presents three datasets, which highlight RO-specific gene expression signatures and reveal differences in gene expression across the three RO regions during development and in adulthood. The integration and rigorous validation of these datasets will advance our understanding of the RO's roles in ovarian development, female maturation, and adult female fertility.

Cyst of rete ovarii: A case report.

Rete ovarii giving rise to cysts, and benign and malignant tumors is a rare entity. Radiological and histopathological examinations can be used to make the diagnosis of rete cyst and differentiate it from cystic tumor of ovarian origin, with surgery being the treatment of choice.

Integration of mouse ovary morphogenesis with developmental dynamics of the oviduct, ovarian ligaments, and rete ovarii.

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending from the ovary into the ovarian capsule. Using genetic mouse models in which the oviduct and RO are perturbed, we found the oviduct is required for ovary encapsulation. This study reveals novel relationships among the ovary and surrounding tissues and paves the way for functional investigation of the relationship between architecture and differentiation of the mammalian ovary.

In humans and other mammals, the female reproductive organs, or ovaries, develop early in life, while the young are still in their mother's womb. Ovaries contain several different compartments, including the ovarian follicles. These are small groups of cells that produce reproductive hormones, and each follicle also has the potential to produce one egg for fertilisation. The ovaries are further surrounded by different tissues that develop alongside them. These include the oviducts, which carry fertilised eggs from the ovaries into the womb, and ligaments, which anchor the ovaries to the wall of the body cavity. During the development of ovaries, ovarian follicles are sorted into two distinct groups. The first, called medullary follicles, are lost before puberty. The second group, or cortical follicles, remain in a state of 'suspended animation' until puberty. After that, they act as a 'reserve' of eggs for the rest of the reproductive lifespan. Once each cortical follicle has produced an egg, it is not replenished. This means that proper follicle sorting is crucial for establishing female fertility, and therefore the ability to conceive. The mechanisms behind follicle sorting, however, are still poorly understood. McKey et al. set out to determine how the ovary's structure changed during its development. In the experiments, high-resolution microscopy techniques were used to reconstruct ovaries of mice in 3D across different stages of development. This revealed that the ends of each ovary started folding towards each other just before birth, and that the folding also happened at the same time as follicle sorting. Simultaneous changes in the shape and orientation of the ligaments suggested that these tissues might direct the folding, for example by pushing or pulling on the rest of the ovary. These results suggest that the changes in ovary structure in early life are critically linked to the establishment of the ovary's egg reserves. McKey et al. hope that this study will pave the way to a better understanding of infertility and, ultimately, better treatments.

Electrolyte, Oestradiol and Progesterone Concentrations in Ovarian Cyst Fluid in Guinea Pigs (Cavia porcellus).

Despite their high prevalence, the aetiopathogenesis of ovarian cysts in guinea pigs (Cavia porcellus) is unknown. We examined tissue samples of cystic ovaries from 20 guinea pigs by histopathology and immunohistochemistry for CD10 antigen, and determined the concentrations of Na+, K+, Cl-, oestradiol and progesterone in the cyst fluid. Cystic rete ovarii were found in all 20 guinea pigs but no follicular cysts. Concentrations of Na+ (142.2 ± 5.04 mmol/l), K+ (5.6 ± 0.76 mmol/l) and Cl- (116.1 ± 5.25 mmol/l) corresponded to extracellular, rather than intracellular, fluid indicating that rete ovarii cysts in guinea pigs are transudative in nature. A positive correlation was found between Na+ and Cl- concentrations (r = 0.7713, P <0.0001). The mean concentrations of oestradiol (61.9 ± 17.44 pg/ml) and progesterone (2.7 ± 5.42 ng/ml) in the cyst fluid were higher than expected because the rete epithelium is not known to have steroidogenic activity. A negative correlation was found between oestradiol and progesterone concentrations in cyst fluid (r = -0.4296, P = 0.0178). Possible pathogenetic mechanisms of cystic rete ovarii in guinea pigs are discussed.

Squamous metaplasia of the rete ovarii do not suppress ovarian cyclicity and pregnancy in cattle: case report / [Metaplasia escamosa da rete ovarii não interrompe a ciclicidade ovariana e a gestação em bovinos: relato de caso]

Squamous metaplasia of the rete ovarii is an ovarian pathologic change characterized by replacement of the normal single layered cuboidal epithelium of the rete ovarii by a stratified squamous keratinized epithelium. Uterus and ovaries from a local slaughterhouse pregnant crossbreed cow were evaluated through ultrasound, macroscopically and histologically. Grossly, there were multiple cysts in both ovaries, which were histologically characterized as rete ovarii cysts with squamous metaplasia and intraluminal accumulation of keratinized material. Squamous metaplasia of the rete ovarii has been previously reported in cows, however this is the first report of this condition in a pregnant animal, demonstrating that this ovarian change is compatible with pregnancy.(AU)

A metaplasia escamosa da rete ovarii é uma patologia ovariana caracterizada pela substituição do epitélio simples cuboidal normal da rete ovarii por um epitélio estratificado escamoso queratinizado. Útero e ovários de uma vaca mestiça gestante, proveniente de abatedouro, foram avaliados por ultrassonografia, macroscopia e histologia. Verificaram-se vários cistos em ambos os ovários, histologicamente caracterizados como cistos de rete ovarii com metaplasia escamosa, com acúmulo intraluminal de material queratinizado. Metaplasia escamosa da rete ovarii foi relatada anteriormente em vacas, porém este é o primeiro relato em que essa alteração ovariana é compatível com manutenção da ciclicidde ovariana e gestação na vaca.(AU)

Brenner tumor associated with rete ovarii: a histologic and immunohistochemical analysis of six cases exploring the relationship between these entities.

The association of Brenner tumor (BT) with rete ovarii (RO) has been rarely alluded to in the literature. Both entities have debatable histogenesis. In this study of six cases of BT associated with RO, we describe the morphologic features and performed immunohistochemical staining for markers of Mullerian, Wolffian, mesothelial, and sex cord stromal derivation to explore the relationship between these entities. Histologically, all BTs were benign, microscopic, and incidental. RO was prominent and hyperplastic with gradual or abrupt transition to BT. In addition, focal areas of rete entrapped between BT nests were seen. All BTs were positive for GATA-3 and negative for PAX-8. Conversely, the RO in all cases was negative for GATA-3 and positive for PAX-8. WT-1 was positive in both entities. Sex cord stromal and mesothelial markers (other than WT-1) were negative in BT and RO. Although morphologically, BTs seem to arise from RO in these cases, they have a distinct immunophenotype. It is possible that at least some BTs arise from metaplastic changes in RO epithelium.

Proceedings of the 2018 National Toxicology Program Satellite Symposium.

The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included seminiferous tubule dysgenesis in rats, ameloblast and odontoblast degeneration/necrosis in a Sprague Dawley rat, intestinal leiomyositis in a beagle dog, gallbladder mucinous hyperplasia, focus of hepatocellular alteration and bile duct alteration in otters, renal tubule cytoplasmic vacuolation with basophilic granules in mice treated swith antisense oligonucleotide therapy, a uterine choriocarcinoma in a rhesus macaque, and rete ovarii proliferative ovarian lesions in various aged rat strains. One particularly provocative lesion was a malignant neoplastic proliferation in the renal pelvic region of a cynomolgus macaque from a 21-day study. Additional challenging lesions included thyroid proliferative lesions in zebra fish and gross findings in fish larvae during routine chemical screening. The Rabbit and Minipig International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups also presented a series of challenging lesions.

Histology of the Ovary of the Laying Hen (Gallus domesticus).

The laying hen (Gallus domesticus) is a robust animal model for epithelial ovarian cancer. The use of animal models is critical in identifying early disease markers and developing and testing chemotherapies. We describe the microscopic characteristics of the normally functioning laying hen ovary and proximal oviduct to establish baselines from which lesions associated with ovarian cancer can be more readily identified. Ovaries and oviducts were collected from 18-month-old laying hens (n = 18) and fixed in 10% neutral buffered formalin. Hematoxylin- and eosin-stained sections were examined by light microscopy. Both post-ovulatory follicular regression and atresia of small follicles produce remnant clusters of vacuolated cells with no histological evidence that scar tissue persists. Infiltrates of heterophils are associated with atresia of small follicles, a relationship not previously documented in laying hen ovaries. Because these tissues can be mistaken for cancerous lesions, we present a detailed histological description of remnant Wolffian tissues in the laying hen ovary. Immunohistochemical staining for pancytokeratin produced a positive response in ovarian surface epithelium and staining for vimentin produced a positive response in granulosa cells of follicles. Epithelial cells lining glands of the remnant epoöphoron had a positive response to both pancytokeratin and vimentin, a result also observed in women.

Ovarian lesions in 44 rabbits (Oryctolagus cuniculus).

The clinical and pathological records of 44 domestic, female rabbits with an age ranging from 6-124 months (median age: 63.5 month) were assessed retrospectively for ovarian lesions. Included were all rabbits that underwent an ovariohysterectomy with a subsequent pathological examination of the genital tract between March 1997 and June 2016. Pathological examination revealed ovarian lesions in 12 of the 44 rabbits including follicular cysts (n=7), cystic rete ovarii (n=3), widespread ovarian necrosis with dystrophic calcification (n=2), ovarian adenoma (n=1). Clinical examination including radiographs only suggested ovarian disorders in two cases of ovarian necrosis with dystrophic calcification and in two cases of cystic rete ovarii. Clinical significance was only conclusive in a case of cystic rete ovarii.

Spontaneous reproductive pathology in female guinea pigs.

Reproductive pathology of domestic guinea pigs is underreported to date. To provide a comprehensive review of uterine disease in guinea pigs, we performed a retrospective study of the pathology archives of the University of Tennessee, College of Veterinary Medicine. By histology, 13 of 37 uterine lesions in 23 animals were neoplastic; the other 24 nonneoplastic lesions included cystic endometrial hyperplasia (16 of 24), endometrial hemorrhage (3 of 24), pyometra (2 of 24), polyp (2 of 24), and mucometra (1 of 24). The most common guinea pig uterine neoplasms were uterine leiomyomas (6 of 13), followed by adenomas (3 of 13) and leiomyosarcomas (1 of 13). Other neoplasms included anaplastic tumors of unknown origin (2 of 13) and choriocarcinoma (1 of 13). Both anaplastic tumors and the choriocarcinoma were positive for vimentin. The choriocarcinoma was positive for HSD83B1, indicating a trophoblastic origin and its final diagnosis. All were negative for cytokeratin and smooth muscle. In multiple animals, more than 1 tumor or lesion was reported. Estrogen receptor and progesterone receptor expression was nearly 100% in uterine neoplasms. Nearly all animals for which data were available had cystic rete ovarii (18 of 19); the animal with no cystic rete ovarii had paraovarian cysts. In our study, female pet guinea pigs had a tendency to develop cystic endometrial hyperplasia and uterine neoplasia. Factors for the development of these lesions could be cystic rete ovarii, hormone dysregulation, and/or age. Other factors could contribute to the development of uterine lesions. As in other species, early ovariohysterectomy could decrease the prevalence of uterine lesions.

Clinical and pathological presentation of squamous metaplasia of the rete ovarii in a Zebu cow / Apresentação clínica e patológica de um caso de metaplasia escamosa da rete ovariana em vaca Zebu

Squamous metaplasia of rete ovarii is characterized by replacement of the normal cuboidal epithelium of rete ovarii by a keratinized stratified scamous epithelium, leading to accumulation of keratinized material within the tubules and cystic dilatation of rete ovarii. The present study decribes a case of scamous metaplasia of rete ovarii in a 10 year old Zebu cow, including clinical, surgical, ultrasonographic, histopathological and hormonal findings. At first ultrasound examination the cow had lightly asymmetric ovaries with follicles presenting echogenicity similar to luteinized follicular cysts. After transvaginal follicular aspiration creamy yellowish sanguineous-purulent content was recovered. After unilateral ovariectomy the ovary was sectioned and brownish viscous material drained from cystic cavity. Histopathology confirmed the diagnosid of squamous metaplasia of the rete ovarii. Progesterone concentrations assessed by chemiluminescent enzyme immunoassay within different time periods after ovariectomy showed that pathology did not compromise normal luteal ovarian activity in a contralateral reminiscent ovary.

A metaplasia escamosa de rete ovarii é caracterizada pela substituição do epitélio cúbico normal da rete ovarii por um epitélio escamoso estratificado queratinizado, levando ao acúmulo de material queratinizado dentro dos túbulos e à dilatação cística da rete ovarii. O presente estudo descreve um caso de metaplasia escamosa de rete ovarii em uma vaca Zebu de aproximadamente 10 anos, incluindo aspectos clínico, cirúrgico, ultrassonográfico, histopatológico e dos achados hormonais. Ao primeiro exame ultrassonográfico, a vaca tinha ovários levemente assimétricos e com folículos apresentando ecogenicidade semelhante à dos cistos foliculares luteinizados. Após a aspiração folicular por via transvaginal, foi recuperado conteúdo sanguinopurulento amarelado e de aspecto cremoso. Após a ovariectomia unilateral, o ovário foi seccionado, permitindo a drenagem de material de aspecto viscoso amarronzado da cavidade cística. A histopatologia confirmou o diagnóstico de metaplasia escamosa da rete ovarii. As concentrações de progesterona avaliadas por quimioluminescência, em diferentes períodos de tempo após a ovariectomina unilateral, mostrou que a patologia não comprometeu a atividade ovariana normal do ovário contralateral remanescente.

Ovarian cystic disease in guinea pigs.

Ovarian cysts are nonfunctional, fluid-filled cysts that develop spontaneously near the ovaries throughout the female guinea pig's reproductive cycle, reducing fertility in females older than 15 months and causing potentially serious uterine disorders. Permanent treatment requires ovariohysterectomy or ovariectomy. This article reviews the clinical signs, diagnosis, histopathology, treatment (including hormonal therapies), surgery, and postoperative care.

Ovarian cysts in the guinea pig (Cavia porcellus).

This article reviews ovarian cysts in the guinea pig (Cavia porcellus), a disease commonly associated with symmetric, nonpruritic alopecia of the dorsum and flanks. Relevant anatomy is discussed and current theories of pathogenesis are reviewed. Prevalence, predisposing factors, diagnosis, treatment, and prognosis are presented.