Uterine histopathology and steroid metabolism in a polycystic ovary syndrome rat model.

The aim of this study was to investigate uterine lesions, uterine endocrine status and expression of genes involved in uterine differentiation in a rat model of polycystic ovary syndrome (PCOS). The possible involvement of the androgen receptor (AR) was also investigated. PCOS rats showed an increased incidence of uterine epithelial and glandular lesions and elevated serum testosterone level, which was not detected in uterine tissue. Uterine 17ß-estradiol, estrone and progesterone were detected in 100%, 75% and 50% of the animals, respectively. This was associated with a decrease in Star and an increase in Hsd17b2, Srd5a1 and Cyp19a1, suggesting that uterine steroids are not synthesized de novo in PCOS and that alterations in these enzymes may explain the absence of testosterone and low progesterone. In addition, ESR2 decreased and AR increased, suggesting possible steroid receptor crosstalk. Genes associated with uterine differentiation, PTEN and WNT5a, also showed reduced expression. PCOS rats treated with flutamide, an AR antagonist, were similar to PCOS rats in terms of uterine lesions, serum steroid levels, ESR2, PTEN and WNT5a expression. However, testosterone, AR and aromatase levels were similar to control rats, with decreased expression of ESR1 and HOXA10, suggesting that these expressions are AR dependent. Our results suggest that the primary cause of the observed uterine lesions in the PCOS rat model is the altered endocrine status and consequently changes in genes related to uterine differentiation.

Assessment of Changes in the Cesarean Scar and Uterus Between One and Two Years after Cesarean Section Using 3D T2w SPACE MRI.

Objective To evaluate changes in morphology of the cesarean scar and uterus between one and two years after cesarean section using high-resolution, three dimensional T2-weighted sampling perfection with application optimized contrast using different flip angle evolutions Magnetic Resonance Imaging (3D T2w SPACE MRI). Methods This prospective study was performed to investigate morphological changes in the cesarean scars and uterus from one to two years after cesarean section using high-resolution, 3D T2w SPACE MRI. The healthy volunteers having no childbearing history were recruited as the controls. All data were measured by two experienced radiologists. All data with normal distribution between the one-year and two-year groups were compared using a paired-sample t test or independent t test. Results Finally, 46 women took a pelvic MR examination one year after cesarean section, and a subset of 15 completed the same examination again after two years of cesarean section. Both the uterine length and the anterior wall thickness after two years of cesarean section (5.75 ± 0.46 and 1.45 ± 0.35 cm) were significantly greater than those measured at one year (5.33 ± 0.59 and 1.25 ± 0.27 cm) (t = -2.363 and -2.175, P= 0.033 and 0.048). No significant difference was shown in myometrial thickness two years after cesarean section (1.45 ±0.35 cm) with respect to the control group (1.58 ± 0.21 cm, P= 0.170). Nine women who underwent MRI twice were considered to have scar diverticula one year after cesarean section, and still had diverticula two years after cesarean section. The thickness, height, and width of the uterine scar showed no significant change from one to two years (all P > 0.05). Conclusions 3D T2w SPACE MRI provides overall morphologic details and shows dynamic changes in the scar and the uterus between one and two years after cesarean section. Scar morphology after cesarean section reached relatively stable one year after cesarean section, and uterine morphology was closer to normal two years after cesarean section.

Prediction of pain intensity with uterine morphological features and brain microstructural and functional properties in women with primary dysmenorrhea.

Primary dysmenorrhea (PDM), defined as painful menstrual cramps of uterine origin, could cause brain structural and functional changes after long-term menstrual pain. Here, we aimed to investigate the predictive value of uterine morphological features and microstructural/functional properties of the brain extracted from periovulatory phases for the intensity of menstrual pain as rated by women with PDM during their subsequent menstrual period. Forty-five women with PDM were recruited and classified into the high and mild pain intensity groups. Pelvic MRI was employed to extract the uterine texture features. White matter diffusion properties, grey matter and functional connectivity features were extracted as brain features. Multivariate logistic regression models with iteration optimization were built for classifying different pain intensity groups. Texture features from myometrium and uterine junction zone had outstanding prediction performance with an area under the receiver operating characteristic (AUC) of 0.96 (P < 0.05, permutation test), and diffusion properties along the thalamic fiber bundles were the most discriminative features with AUC of 0.95. Applying features from uterus and brain together, we could gain better prediction performance. Our results indicated that accumulated differences in menstrual pain were associated not only with uterine structure but also diffusion properties of thalamic-related fiber tracts, suggesting that treatment options of PDM patients may be expanded from only being able to manage pain in the uterus focusing on the functional/structural modifications of the pain processing system.

Uterine and eggshell modifications associated with the evolution of viviparity in South American water snakes (Helicops spp.).

The evolution of viviparity requires eggshell thinning to bring together the maternal uterus and extraembryonic membranes to form placentae for physiological exchanges. Eggshell thinning likely involves reduced activity of the uterine glands that secrete it. We tested these hypotheses by comparing the uterine and eggshell structure and histochemistry among oviparous and viviparous water snakes (Helicops) using phylogenetic methods. Eggshell thinning occurred convergently in all three origins of viviparity in Helicops and was accomplished by the loss of the mineral layer and thinning of the shell membrane. Uterine glands secrete the shell membrane in both oviparous and viviparous Helicops. These glands increase during vitellogenesis regardless of the reproductive mode, but they always reach smaller sizes in viviparous forms. As there is no phylogenetic signal in eggshell thickness and gland dimensions, we conclude that interspecific differences are related to reproductive mode and not phylogeny. Therefore, our results support the hypothesis that eggshell thinning is associated with the evolution of viviparity and that such thinning result from a reduction in gland size in viviparous taxa. Interestingly, the shell membrane thickness of viviparous females of the reproductively bimodal Helicops angulatus is intermediate between their oviparous and viviparous congeners. Thus, although eggshell thinning is required by the evolution of viviparity, a nearly complete loss of this structure is not. However, uterine gland dimensions are similar across viviparous Helicops. Fewer glands or their functional repurposing may explain the thinner shell membrane in viviparous species of Helicops in comparison to viviparous females of the bimodal H. angulatus.

Uterine and eggshell modifications associated with the evolution of viviparity in South American water snakes (Helicops spp.)

The evolution of viviparity requires eggshell thinning to bring together the maternal uterus and extraembryonic membranes to form placentae for physiological exchanges. Eggshell thinning likely involves reduced activity of the uterine glands that secrete it. We tested these hypotheses by comparing the uterine and eggshell structure and histochemistry among oviparous and viviparous water snakes (Helicops) using phylogenetic methods. Eggshell thinning occurred convergently in all three origins of viviparity in Helicops and was accomplished by the loss of the mineral layer and thinning of the shell membrane. Uterine glands secrete the shell membrane in both oviparous and viviparous Helicops. These glands increase during vitellogenesis regardless of the reproductive mode, but they always reach smaller sizes in viviparous forms. As there is no phylogenetic signal in eggshell thickness and gland dimensions, we conclude that interspecific differences are related to reproductive mode and not phylogeny. Therefore, our results support the hypothesis that eggshell thinning is associated with the evolution of viviparity and that such thinning result from a reduction in gland size in viviparous taxa. Interestingly, the shell membrane thickness of viviparous females of the reproductively bimodal Helicops angulatus is intermediate between their oviparous and viviparous congeners. Thus, although eggshell thinning is required by the evolution of viviparity, a nearly complete loss of this structure is not. However, uterine gland dimensions are similar across viviparous Helicops. Fewer glands or their functional repurposing may explain the thinner shell membrane in viviparous species of Helicops in comparison to viviparous females of the bimodal H. angulatus.

Quercetin Induces Dose-Dependent Differential Morphological and Proliferative Changes in Rat Uteri in the Presence and in the Absence of Estrogen.

Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be attributed to quercetin's estrogenic properties.

Sex hormone replacement in ovarian failure - new treatment concepts.

Premature ovarian failure is associated with decreased bone mass and fractures, and an increased risk of premature death from cardiovascular disease. There is also fertility compromise associated not only with the loss of ovarian function but, in those with pre-pubertal POF, inadequate uterine morphology. A wide variety of hormone replacement regimes are reported, but there is no clear evidence of best practice. Hormone replacement therapy (HRT) and the combined oral contraceptive pill (COCP) will suppress menopausal symptoms; however neither is designed to achieve physiological replacement of oestrogen and progesterone. There is evidence that physiological sex steroid replacement is superior to standard hormone replacement, in improving uterine volume as well as an improved blood pressure profile and bone mineral density. Sex steroid replacement therapy is long-term in these women, and therefore it is essential that the risk benefit ratio is optimal to maximise longer term health.

Sophoricoside fails the embryo implantation by compromising the uterine endometrial receptivity at implantation "window" of pregnant mice.

Sophoricoside (SOPH) is an isoflavone glycoside isolated from the fruits of Sophora japonica. Since its first isolation in 1961, there are rare findings about the effects of SOPH on reproductive system. In the present study, the pregnant mice administrated by different doses of SOPH were used to explore the effect of SOPH on embryo implantation, especially on the endometrial receptivity. The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of SOPH. When the administrated dose of SOPH was 600 mg/kg per day, great changes were observed in the exposed uterine morphology and up-regulated progesterone receptor (PR) and down-regulated estrogen receptor α (ERα), E-cadherin, matrix metalloproteinase-2 (MMP-2) and integrin ß3 were also found in SOPH-exposed uterine. These findings demonstrated that SOPH exposure reduced the number of implanted embryos in a dose-dependent manner and failed the embryo implantation through altering the morphology of uterine and compromising the endometrial receptivity.