Cat Uterus Research Articles

INDICATION FOR ELECTIVE OR THERAPEUTIC SURGICAL STERILIZATION IN DOGS AND CATS: Integrative Review

Castration is the most recommended surgical procedure in small animal clinics and consists of removing the ovaries, uterus and uterine tubes of dogs and cats with the aim of avoiding unwanted pregnancies and treating and preventing reproductive illnesses. This literature review seeks to offer a broad view of the indication for castration, observing whether this surgical technique is more suitable for treating illnesses or as a contraceptive measure, the owners' perceptions of the procedure and its impact on public health. The methodology used was an integrative literature review, delimiting the topic and then searching for recent articles related to the topic, using sources such as Google Scholar, Scielo, PubMed, magazine journals and books using keywords, specific issues such as “Castration in dogs and cats”, “Contraception for dogs and cats”, “Reproductive diseases in dogs and cats”. The analysis of the articles identified that elective castration is an important means of preventing diseases of the reproductive tract and uncontrolled reproduction and is highly recommended in small animal veterinary clinics, however, most owners choose to carry it out only in cases involving pathologies. It is necessary to educate the population about the benefits of neutering and government platforms must be charged with free population control projects for these animals.

A comparative histological, histometrical and hormonal study between the ovary and uterus of non-pregnant and pregnant local breed cat (Catus felius)

A comparative histological, histometrical and hormonal study between the ovary and uterus of non-pregnant and pregnant local breed cat (Catus felius)

Use of contraceptives in cats with ovarian and uterine pathology

Regulation of the reproductive capacity of cats using megestrol acetate (a gestagenic preparation) contributes to the development of pathological processes in the uterus, ovaries, and imbalance of gonadal hormones. Therefore, it is essential to investigate and scientifically substantiate the pathogenetic processes in the body of cats under medical contraception. The purpose of this study was to substantiate the pathomorphological changes and dynamics of certain blood parameters in the body of cats under the use of megestrol acetate. The study employed clinical (examination, palpation), laboratory (haematological, biochemical, hormonal), morphological (examination of the genital organs of cats amputated during ovariohysterectomy) methods. A decrease in ovarian size in hypotrophic cats by 11.3×9.05% was found compared to the ovaries of healthy cats. The dependence of megestrol acetate administration on the occurrence of cystic formations in the ovaries was found, with an increase in ovaries in the experimental group by 1.7×2.47 times in follicular cysts and by 1.9×3.1 and 2.5×3.9 times in luteal cysts and polycystic cysts, respectively. It was found that the uterus in cats with megestrol acetate was increased by 3.16×1.93 times in the right horn and 2.84×2.1 times in the left horn compared to the uterus of healthy cats. The dynamics of progesterone (increase by 37.85%), follicle-stimulating hormone (decrease by 43.75%) and oestradiol (increase by 72.15%) were determined in comparison with intact animals. The increase in serum glucose levels in cats after megestrol administration by 34.31%, total protein by 25.0% and creatinine by 11.10%, aspartate aminotransferase by 43.84% (1.78 times) and alanine aminotransferase by 49.84% (1.99 times), and serum urea by 58.71% was substantiated. At the same time, haemoglobin levels decreased by 16.5%. The findings of this study can be used in the development of new methods and regimens of medical contraception with minimisation of risks of complications of the reproductive system, regulation of reproductive capacity, and prevention of infertility in cats

Pyometra alters the redox status and expression of estrogen and progesterone receptors in the uterus of domestic cats.

The aim of this study was to evaluate the expression profile of sex steroid receptors and redox mediators in the uterus of domestic cats with pyometra. Twelve cats were used and divided into groups: (1) non-gestational healthy diestrus (n = 7) and (2) pyometra (n = 5). The plasma profiles of estradiol and progesterone (P4) as well as uterine expression levels of estradiol alpha (ERα), progesterone (PR) and androgen (AR) receptors, of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1), and of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were evaluated. Cats with pyometra showed higher plasma P4 levels and increased uterine messenger RNA (mRNA) and protein expression of ERα and PR, mainly in the glandular epithelium for ERα and in stromal and myometrial cells for PR. In addition, there was an increase in 8-OHdG immunostaining and GPX1 mRNA and protein expression in cats with pyometra compared with those in non-gestational diestrus, while catalase showed a reduction in endometrial immunostaining in cats with pyometra. There were no differences in uterine AR and SOD1 expression between the groups. The findings of this study showed that pyometra is associated with oxidative stress in the uterus of domestic cats and alterations of the profile of sex steroid receptors, especially ERα and PR, and of antioxidant enzymes, suggesting that changes in these mediators may play a role with the etiopathogenesis of this disease.

Histological changes in the uterine and ovarian walls in pyometra

In recent years, the number of small domestic animals, which have become cohabitants of people both in cities and in rural areas, has increased significantly. Keeping cats indoors with the use of artificial lighting has led to the fact that anestrus falls out of their sexual cycle, and the stages of arousal are manifested in them throughout the year. This phenomenon is the cause of various inflammatory processes in the uterus. The most common gynecological diseases in cats are pyometra, endometritis, and vaginitis. Violation of the hormonal status in the hypothalamus-pituitary chain in the absence of contact with natural partners is accompanied by a disorder of the function of the ovaries and uterus. A change in the hormonal balance, manifested by a violation of the ratio of estradiol and progesterone concentrations in the blood, affects the function of the endometrium and provokes an increase in the secretory activity of the uterine glands. Initiated in the arousal stage of the sexual cycle, it does not fade away but progresses even more. This is how the conditions for the emergence of an inflammatory process in the uterus are created and maintained. The course of the disease is accompanied by persistent morphological changes in the state of the uterus and all organs and their systems. Diagnosis of the disease is well-developed and does not present any difficulties in veterinary clinical practice. However, the approaches to substantiating the etiology and pathogenesis of the disease and the effectiveness and expediency of a conservative or operative treatment method are controversial. There are also limited reports on the histostructure of certain areas of the fallopian tubes and uterus, depending on the functional state of the cat’s body. The research aimed to investigate the histological structure of the uterus and ovaries of cats with pyometra. Ten explanted uteri and ovaries were subjected to histological examination in 10 cases of surgical treatment of cats with pyometra. In this research, it has been established that the pathohistological changes of the uterine wall due to pyometra are characterized by endometrial hypertrophy, the basis of which is hyperplasia with the formation of various forms of outgrowths covered with epithelium, followed by their dystrophy and the formation of detritus, which locally sticks to the endometrium and fills the uterine cavity, local desquamation of the serous mesothelium membrane, compaction of the muscular membrane, loosening of the vascular membrane, and dilatation of veins. The surface parts of the endometrial glands undergo dystrophic changes and cystic degeneration, manifested by hyperplasia of their walls and the formation of cavities filled with detritus of desquamated epithelium and cavities of “empty cysts” filled with remnants of detritus. Deep sections of the endometrial glands are reduced, but their histostructure is not transformed. Changes in the ovaries are manifested by focal desquamation of the mesothelium, the formation in the depth of the cortical substance of mainly one voluminous corpus luteum, atresia of follicles, and the presence of full-fledged tertiary follicles.

Estrogen and progesterone receptors and antioxidant enzymes are expressed differently in the uterus of domestic cats during the estrous cycle

Sex steroids and antioxidant enzymes are important in female sexual development and adequate modulation of the estrous cycle, pregnancy, and fetal development. Therefore, modifications in its signaling or expression in the genital system are associated with reproductive dysfunctions. However, the spatial-temporal expression profile of receptors for sex steroids and antioxidant enzymes in the uterus of domestic cats throughout the estrous cycle needs to be studied. Cats in proestrus/estrus (N = 6), diestrus, (N = 7), and anestrus (N = 6) were used to evaluate the uterine expression of estrogen alpha (ERα), progesterone (PR), and androgen (AR) receptors and of the antioxidant enzymes superoxide dismutase 1 (SOD1), catalase and glutathione peroxidase 1 (GPX1) by immunohistochemistry and qPCR. The uterus of cats in diestrus showed lower protein and mRNA expression of ERα and PR compared to proestrus/estrus and anestrus, mainly in the luminal and glandular epithelium and myometrium, different from catalase and SOD1, which showed higher expression in diestrus in relation to other phases of the cycle. GPX1, on the other hand, showed lower uterine gene expression in diestrus compared to proestrus/estrus and anestrus. No significant differences in AR expression were observed. In conclusion, ERα and PR sex steroid receptors and antioxidant enzymes are expressed differently in the uterus of domestic cats during the estrous cycle.

Distribution of Connective Tissue Fibres in the Feline Ovary and Uterus

Connective tissue is significant because it is one of the supporting tissues, it connects organs and keeps them in place, it contains inflammatory response components, and it provides the environment in which metabolic exchange occurs between cells. Collagen fibres are the most common type of connective tissue component. Type 3 collagen, glycoproteins, and proteoglycans make up reticular fibres. They allow the uterus and ovaries to contract and stretch since they are situated in between the muscles and collagen fibres in these organs. According to the requirements of the microenvironment in which they are found, elastic fibers have persistent changeable functionalities and are resistant to tensile forces. After regular histological tissue follow-up after washing, tissues removed from the ovaries and uterus of cats were fixed in 10% formaldehyde and blocked in the paraplast. Sections from the prepared blocks were cut at a thickness of 5–6 µm. The distribution and structure of these yarns were studied using the methods of Orsein for the structure of elastic yarns derived from connective tissue yarns, Van Gieson's for the structure of collagen yarns, and Gordon and Sweet's dyeing process for the structure of reticulum yarns. It was determined that the ovary and uterus had increased collagen fiber dispersion. Less dispersion was observed in reticulum and elastic fibres. The collagen fibres in the elastic and reticulum fibres, which were arranged in thick bundles between the follicles in the ovary, were found to have a thinner structure. It was noted that the collagen fibres were more thickly distributed in the lamina propria of the uterine endometrium, where the elastic and reticulum fibres were formed from thin filaments.

Kisspeptin/Kiss1r system and angiogenic and immunological mediators at the maternal-fetal interface of domestic cats.

The Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone and luteinizing hormone release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N=6) and late pregnancy (N=6), in addition to uterus from non-pregnant cats in diestrus (N=7), to evaluate protein and gene expression of kisspeptin (Kiss1), kisspeptin receptor (Kiss1r), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (Flk-1), placental growth factor (PLGF), interferon gamma (INFγ), migration inhibiting factor (MIF), tumor necrosis factor (TNFα), interleukins (IL6 and IL10) by immunohistochemistry and quantitative polymerase chain reaction. Pregnancy increased the uterine expression of Kiss1 and Kiss1r, especially at the late pregnancy, in addition to upregulating INFy, MIF, Vegf, Il10, and Tnf and downregulating Plgf. Higher placental expression of Kiss1r and Plgf mRNA occurred at the late pregnancy, while the expression of Kiss1, VEGF, Flk-1, INFy, TNFα, Il6, and IL10 was higher in the mid of pregnancy. A positive correlation between Kiss1 and Tnf was observed in the placenta, while Kiss1r had a negative correlation with Infγ, Il6, and Il10. The findings reveal that Kisspeptin/Kiss1r and angiogenic and immunological mediators at the maternal-fetal interface of pregnant cat have a gene correlation and are modulated by the gestational age. These data suggest possible functional links of Kisspeptin in placental angiogenesis and immunology.

To the doctrine of uterine innervation

On the basis of studies carried out on the uterus of people, dogs, cats and rabbits, A. comes to the following conclusions.

Pyometra and estrous cycle modulate the uterine expression of the kisspeptin system and angiogenic and immune factors in cats.

Failures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INFγ, MIF, TNFα, and IL10. These factors were positively correlated with Kiss1 and/or Kiss1r, and a positive correlation between Kiss1 and Kiss1r was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kiss1r on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and Il6 mRNA, and an increase in Tnf mRNA. The findings reveal that there is a gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of the domestic cat, which is modulated by the estrous cycle, and that pyometra affects the expression of these mediators. This study suggests, for the first time, a functional relationship between the Kiss/Kiss1r system and angiogenic and immune mediators in the female genital tract.

Influence of some etiological factors on development of gynecological patholo-gy and infertility of cats

The article provides an overview of professional literature on reproductive studies of cats, the definition of the main factors influencing the development of infertility in cats: hormonal changes, lack of sufficient stimulus during pairing, leading to ovulation, inability to fuse, ovarian cyst, chronic inflammatory processes in reproductive organs systems, infections, some parasites or the simplest, hereditary problems, including chromosomal abnormalities (genetic or congenital defects such as pseudoharmophioditis, true hermaphroditism, mosaicism, infantilism, freemantry) described congenital aplasia of the ovaries, trauma affecting the reproductive organs. The conditions of detention that considerably affect the reproductive system are considered. It has been established that insufficient stimulation is one of the most common causes of infertility, which is relevant for cats because they are characterized by induced ovulation. Most animals with an abnormal set of sex chromosomes are infertile, treatment methods have not been developed. Inadequate feeding is perhaps the most important cause of infertility in cats. The connection between lack and (or) excess in the diet of Calcium, Phosphorus, Iodine, Cobalt, Cuprum, Manganese, other macro-and micro elements, and inability to reproduce is established. The role of microorganisms in the emergence of infertility of cats of infectious diseases (leukemia, infectious peritonitis, panleukopenia, chlamydia, toxoplasmosis) is considered. Extension of the intraperitoneal period arises from the stage of the anestrus. Such clinical picture is observed in cats older than 8 years with hypothyroidism and hyperadrenocorticism, obesity and cachexia, the appointment of drugs with antinuclear activity. Among gynecological diseases in cats, the most common diseases are pyometra, endometritis and vaginitis. It has been established that the most frequently diagnosed diseases of the uterus of female dogs and cats are cystular hyperplasia of the endometrium in combination with the pythometer, data on the etiopathogenesis of these diseases is given. The scientific data on the application of ultrasound diagnostics, hormonal level studies, vaginal cytology, the use of hysterosalpingography, x-ray for more accurate diagnostics of causes of infertility of cats are given.

Inhibitory effect of Bisphenol A on in vitro feline uterine contractions

Bisphenol A (BPA) is an environmental pollutant used as a plasticizer in the manufacture of many plastic products, such as packaging, containers, and water and beverage bottles. There are deleterious effects of BPA on metabolic, endocrine, nervous, and reproductive systems. This is the first study in which there was investigation of the in vitro effect of BPA on the spontaneous contractions of the cat uterus. The tubal uterine segments (1 cm) collected from queens in estrus were suspended in an isolated organ bath. Following tissue stabilization, spontaneous contractions were recorded for 10 min to constitute the control group. The effects of the solvent (alcohol) and BPA at different concentrations (1, 10, and 100 μM) on uterine contractions were subsequently evaluated at 10 min intervals in terms of frequency and mean amplitude variables. The ethanol vehicle did not alter the uterine contractions compared to the control group. All concentrations of BPA used in the study resulted in a reduction (P < 0.05) in amplitude of uterine contractions in a dose-dependent manner, while only the largest dose of BPA decreased the frequency of contractions (P < 0.05). In reproductive physiology, regular uterine contractions facilitate successful fertilization, migration, implantation, and maintenance of pregnancy, as well as fetus expulsion. The results of this study indicate BPA has an inhibitory effect on spontaneous contractions of the cat uterus. It is proposed that this suppressive effect of BPA on uterine contractions might lead to queen infertility.

Ectopic Pregnancy in Two Cats

Background: Ectopic pregnancy mainly refers to tubal pregnancy and abdominal pregnancy. Tubal pregnancy presents as an implanted embryo that develops in the fallopian tubes, and is relatively common in humans. In animals, tubal pregnancy occurs primarily in primates, for example monkeys. The probability of a tubal pregnancy in non-primate animals is extremely low. Abdominal pregnancy is a type of ectopic pregnancy that occurs outside of the uterus, fallopian tube, ovary, and ligament(broad ligament, ovarian ligament, suspensory ligament).This paper describes two cases of ectopic pregnancy in cats.Cases: Cat 1. The presenting sign was a significant increase in abdominal circumference. The age and immune and sterilization status of the cat were unknown. On palpation, a 4 cm, rough, oval-shaped, hard mass was found in the posterior abdomen. Radiographic examination showed three high-density images in the posterior abdomen. The fetus was significantlycalcified and some feces was evident in the colon. The condition was preliminarily diagnosed as ectopic pregnancy. Cat 2. The owner of a 2-year-old British shorthair cat visited us because of a hard lump in the cat’s abdomen. The cat had a normal diet and was drinking normally. Routine immunization and insect repulsion had been implemented. The cat had naturally delivered five healthy kittens two months previous. Radiographs showed an oval-shaped mass with a clear edge in the middle abdominal cavity. Other examinations were normal. The case was preliminarily diagnosed as ectopic pregnancy, and the pregnancy was surgically terminated. The ectopic pregnancies were surgically terminated. During surgery, the structures of the uterus and ovary of cat 1 were found to be intact and the organs were in a normal physiological position.Cat 1 was diagnosed with primary abdominal pregnancy. In cat 2, the uterus left side was small and the fallopian tube on the same side was both enlarged and longer than normal. Immature fetuses were found in the gestational sac. Thus, cat 2 was diagnosed with tubal ectopic pregnancy based on the presenting pathology.Discussion: Cats with ectopic pregnancies generally show no obvious clinical symptoms. The ectopic fetus can remain within the body for several months or even years. Occasionally, necrotic ectopic tissues or mechanical stimulation of the ectopic fetus can lead to a systemic inflammatory response, loss of appetite, and apathy. The two cats in our reportshowed no significant clinical symptoms. To our knowledge, there have been no previous reports of the development of an ectopic fetus to maturity, within the abdominal cavity of felines, because the placenta of cats cannot support the growth and development of the fetus outside of the uterus. Secondary abdominal ectopic pregnancy, lacking any signs of uterine rupture is likely associated with the strong regenerative ability of uterine muscles. A damaged uterus or fallopian tube can quickly recover and rarely leaves scar tissue. In the present report, cat 1 showed no apparent scar tissue, nor signs of a ruptured ovary or fallopian tubes. It was diagnosed with primary ectopic abdominal pregnancy, which could arise from the descent of the fertilized egg from the fallopian tube into the abdominal cavity. There was an abnormal protrusion in left of the fallopian tubes in cat 2, to which the gestational sac was directly connected. Based on pathological examination of the uterus, fallopian tubes, and gestational sac, the cat was diagnosed with a tubal pregnancy. Placental tissues and signs of fetal calcification were observed in both the fallopian tube and gestational sac.Keywords: tubal pregnancy, abdominal pregnancy, feline, ectopic fetus, fallopian tube, gestational sac.

Gene expression profiles of some cytokines, growth factors, receptors, and enzymes (GM-CSF, IFNγ, MMP-2, IGF-II, EGF, TGF-β, IGF-IIR) during pregnancy in the cat uterus

Early pregnancy is one of the most critical periods of pregnancy, and many factors such as cytokines, enzymes, and members of the immune system have to cooperate in a balanced way. In the present study, the gene expression profiles of factors associated with pregnancy such as EGF, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, interferon gamma, insulin-like growth factor 2, insulin-like growth factor 2 receptor, and matrix metalloproteinase 2 were analyzed in uterine tissues of female cats. The cats were assigned to five groups: G1 (embryo positive, n = 7; 7th day after mating), G2 (after implantation, n = 7; 20th day after mating), G3 (midgestation, n = 7; 24–25th day after mating), G4 (late gestation, n = 7; 30–45th day after mating), G5 (oocyte group, n = 7; 7th day after estrus). Tissue samples from the uterus and placenta were collected after ovariohysterectomy. Relative messenger RNA levels were determined by real-time polymerase chain reaction. All the factors examined were detected in all tissue samples. In the course of pregnancy, significantly higher expression of EGF and matrix metalloproteinase 2 in G2 than in G1 was observed (P < 0.05). Insulin-like growth factor 2 expression was higher in all groups than in G1 (P < 0.05). Upregulation of EGF during implantation was detected. The expression of interferon gamma was significantly higher in G3 than in G1 (P < 0.05). Transforming growth factor beta and granulocyte-macrophage colony-stimulating factor were constantly expressed in all groups. In conclusion, the expressions of these factors in feline uterine tissue at different stages of pregnancy might indicate that these factors play roles in the development of pregnancy such as trophoblast invasion, vascularization, implantation, and placentation.

Expression of hypoxia-inducible factors and vascular endothelial growth factor during pregnancy in the feline uterus

Hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) have critical roles during the development of the fetomaternal unit. The HIFs regulate placentation and vascularization by stimulation of VEGF gene expression. This study aimed to investigate the expression profiles of HIF gene family and VEGF in the cat uterus during pregnancy. Tissue samples of the whole uterine wall were collected after ovariohysterectomy and allocated to the following groups: embryo positive (group 1 [G1], n = 7, 7 days after mating), early pregnancy (group 2 [G2], n = 7, 20 days after mating), mid-pregnancy (group 3 [G3], n = 7, 24 days after mating), late pregnancy (group 4 [G4], n = 7, 30–45 days after mating), and oocyte positive groups (group 5 [G5], n = 7, 7 days after induction of ovulation with GnRH analog). Relative mRNA levels were determined by real-time polymerase chain reaction. As housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase was used. The relative gene expression of HIF1A in G5 was found to be significantly higher than that of other groups (G1, G2, G3, and G4) (P < 0.05). In addition, the expression of HIF2A in G5 was higher than that of G1 and HIF2A gene expression at placentation sites of G4 was higher than in G1, G2, and G3 (P < 0.05). Immunohistochemistry indicated that HIF1A, HIF2A, and VEGF expressions were observed in different cell types of uterine and placental tissues in late pregnancy and oocyte groups. The expression of HIF3A did not change significantly in any group investigated. These observations suggest that HIFs and VEGF may play a role in the establishment and development of pregnancy.

Expression of platelet activating factors and its receptor in cat uterus during early pregnancy

Platelet activating factors (PAF1β, PAF1γ, PAF:ah, PAF-R) have a significant role during mammalian pregnancy process. This study aimed to investigate expression profiles of PAF gene family in cat uterus during pregnancy. Tissue samples were collected via ovariohysterectomy at days 7 (Gr1; n=3), 18-20 (Gr2; n=7), 24-25 (Gr3; n=5) after mating from the different regions of the uterus. Relative expression levels of genes were quantified using real-time qRT-PCR. A mixed model was fitted on the normalized data and Least Significant Difference (LSD) test was employed to determine significant differences between groups. Expressions of PAF genes were assessed in the cat uterus during pregnancy around implantation period; however, no significant differences were detected between the preimplantation and the implantation stage. Similarly, no significant difference concerning mRNA expression was assessed between different parts of the uterus during pregnancy. In conclusion, PAF genes are expressed in the cat uterus during early pregnancy. However, this expression is not associated with changes in the uterus during early pregnancy

Expression of Survivin, Bcl‐2 and Bax Proteins in the Domestic Cat (Felis catus) Endometrium During the Oestrus Cycle

Apoptosis has been shown to be an important regulator of endometrium function. To clarify the regulation of apoptosis in the cat endometrium during the normal oestrus cycle, the expressions of the apoptosis-related proteins (Bcl-2 and Bax) and their correlation to the inhibitor of apoptosis protein Survivin were analysed using immunohistochemistry. The TUNEL technique (TdT-mediated dUTP nick end labelling) was also used to detect DNA fragmentation characteristic of apoptotic cells. The results demonstrated that TUNEL labelling is not effective for the detection of apoptosis in cat endometrium. Survivin was expressed in the luminal and glandular epithelial cells of cat endometrium during all phases of the oestrus cycle. Survivin was localized in both the cytoplasm and nuclei of superficial and deep uterine gland cells during the luteal phase, while only cytoplasmic staining was observed during the follicular and anoestrus phases. Bax immunoreactivity in the cytoplasm of luminal and glandular epithelial cells as well as the smooth muscle cells of blood vessels was weak in the anoestrus phase. Compared with anoestrus, the intensity of Bax immunostaining was moderate in the follicular phase and increased dramatically in the luteal phase. Bcl-2 immunostaining in the cytoplasm of luminal and glandular epithelial cells was moderate in the anoestrus phase. During the early follicular phase, cytoplasmic Bcl-2 immunostaining was detected mostly in glandular epithelial cells. In the mid-follicular phase, in glands, the amount of Bcl-2 protein increased progressively from the superficial to the deep layer. In contrast, the expression of Bcl-2 decreased in the secretory phase, being very low or absent in the mid- and late luteal phases. The overall results suggest that Survivin, Bax and Bcl-2 proteins may cooperatively contribute to cell apoptosis and cell proliferation in the cat uterus during the oestrus cycle.

Tumor Necrosis Factor-alpha as a possible auto-/paracrine factor affecting estrous cycle in the cat uterus

Tumor Necrosis Factor-alpha (TNFalpha) is a pleiotrophic cytokine, affects either normal or tumor cells, and influences cellular differentiation. TNFalpha role in female reproduction has been proven to be mediated through an influence on prostaglandin (PGs) synthesis and output. To evaluate the possible role of TNFalpha in an auto-/paracrine regulation in the cat uterus, mRNA expression coding for TNFalpha and its receptors (TNFR1 and TNFR2), and TNFalpha protein content at different stages of the estrous cycle were investigated. Additionally, TNFalpha involvement in PG secretion at different stages of the estrous cycle was investigated by in vitro tissue culture. Gene expressions coding for TNFalpha and TNFR1 were the highest at diestrus (P < 0.05). TNFalpha protein expression was the lowest at interestrus (P < 0.05). Nevertheless, TNFR2 was not affected by the estrous stage. TNFalpha at a dose of 1 ng/ml significantly increased PGF2alpha secretion at estrus (P < 0.01) and PGE2 secretion at diestrus (P < 0.001) after 12h incubation. Overall findings indicate that TNFalpha locally produced in the cat's uterus, stimulates PG secretion in an estrous cycle-related manner.

Endometrial Stromal Sarcoma with Smooth Muscle and Glandular Differentiation of the Feline Uterus

The intra-abdominal tumor developing in the uterus and lung of a domestic Shorthair cat was examined histopathologically and immunohistochemically. The tumor showed a proliferation of both endometrial stromal and smooth muscle cells accompanied by prominent vasculature. There were well-differentiated endometrial glands, and tubuli made up a monolayer of eosinophilic cuboidal epithelium. Immunohistochemically, the spindle-shaped cells and half of the stromal-like cells reacted to caldesmon and desmin antibodies. The neoplastic epithelium expressed AE1/AE3 cytokeratin. Feline endometrial stromal tumor has, to the best of our knowledge, not been reported previously and has smooth muscle and glandular components that are a unique variant to the human counterpart.

Steroid Receptor Expression and HER‐2/neu (c‐erbB‐2) Oncoprotein in the Uterus of Cats with Cystic Endometrial Hyperplasia–Pyometra Complex

The presence of oestrogen-alpha receptor (ER), progesterone receptor (PR), and HER-2/neu (c-erbB-2) oncoprotein in the uterine walls of 10 healthy cats and 20 subjects with cystic endometrial hyperplasia-pyometra (CEH-P) were evaluated. Lesions were graded according to the severity of cystic dilation, hyperplasia and inflammation, and were classified as normal, mild uterine hyperplasia and severe uterine hyperplasia. The ER, PR and c-erbB-2 expression in the endometrium, glandular epithelium, stromal fibroblasts and myometrial smooth muscle cells was quantified by immunohistochemistry. The ER, PR and c-erbB-2 staining patterns differed between normal uteri and uteri with CEH-P. The ER expression was tended to be higher in the endometrial surface and glandular epithelium in the severe hyperplasia group (P > 0.05) and significantly lower in the mild hyperplasia cases compared with normal endometrium (P < 0.05), whereas the PR expression in both severe and mild hyperplasia cases tended to be higher in stromal cells and glandular epithelium than those in the normal uteri. C-erbB-2 immunoreactivity was observed only in the endometrial surface and glandular epithelium of the uterine wall and immunostaining was found to be highest in cases with severe hyperplasia. As a conclusion, we suggest that c-erbB-2 oncoprotein may play a role in the pathogenesis of the CEH together with the ER and PR in cats, and that ER does not have a role in the mechanism of pyometra, whereas PR plays a role in the pathogenesis of both CEH and pyometra.