Female Genital Research Articles

Malakoplakia, a rare inflammatory condition presenting as a colon polyp

Abstract Introduction/Objective Malakoplakia is a rare histiocytic disease caused by defects in phagocytic or degradative functions of histiocytes in response to gram negative coliforms (E. coli or Proteus) that results in chronic inflammatory state, followed by intracellular deposition of iron and calcium (known as Michaelis-Gutmann bodies). It’s more common in immunocompromised patients and the mean age at diagnosis is fifth decade. It occurs in all organs, common in GU tract, particularly bladder, but also seen in gastrointestinal tract (most commonly colon, followed by stomach and duodenum), central nervous system and female genital tract. In gastrointestinal tract, it can present as a polyp with diffuse mucosal involvement, submucosal thickening, and even may cause mass. Methods/Case Report A 60 -year-old male smoker presented to our hospital with history of colon polyps; colonoscopy revealed a 6 mm sessile polyp at the hepatic flexure. A biopsy was performed which showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, abundant Michaelis-Gutmann bodies and increased lymphocytes. Immunohistochemical stains showed diffuse positivity for CD68; and PAS stain was positive for histiocytic cytoplasmic granules. Based on this data, the diagnosis of Malakoplakia was confirmed. Malakoplakia is treated with antibiotics that concentrate in macrophages (quinolones or trimethoprim-sulfamethoxazole), antibiotics directed against E. coli, surgery and possibly discontinuation of immunosuppressive drug therapy. Results (if a Case Study enter NA) Malakoplakia, in this case, was presented clinically as a sessile colon polyp and histologically showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, with Immunohistochemical stains (CD68; and PAS stain) the correct diagnosis was made. Other presentations of Malakoplakia include diffuse mucosal involvement, submucosal thickening, or mass. Histologically, it may rarely be mistaken as signet ring carcinoma. These variable presentations in GU tract or colon can be interpreted as malignancy with consequent unnecessary interventions. Hence, awareness of Malakoplakia with careful histopathologic examination and the use of immunohistochemical studies are advisable in that cases. Conclusion We would like to emphasize that Malakoplakia can be clinically and histologically misdiagnosed as a malignant condition; therefore histopathologic and immunohistochemical studies are needed to correctly diagnose this entity.

Conceptual Study on Environmental toxicity as Dushi Visha as Causative Factor in Infertility & its Ayurvedic Management

Exposure to toxic substances in the environment can lead to various health problems that persist over time. These toxic substances can come from multiple sources, such as air pollution, contaminated water, and exposure to hazardous chemicals. Such toxins have hazardous effects on human health. So, one of the effect is on the Reproductive system. Environmental toxins damage normal physiological reactions related to the reproductive system. In today’s era Infertility is one of the burning issues globally. Some studies also told these environmental toxins exposure have hazardous effect on male & female reproductive system.[1] Excessive exposure to pollutants in the environment, long-term exposure of contaminated foods, Water, pesticides, industrial chemicals, toxic metals etc all of which fall under the concept of dushivisha, cause reproductive dysfunctions and infertility. One of the effects of dushivishalinked to infertility is "Kshapayetshukram" (shukramdepletion). In both the lakshana and upadrava of dushivisha, acharya sushrutha mentioned sukrakshaya.[2] So in this study an effort has been put forth to make conceptual study on environmental toxins as Dushi visha as a causative factor of Infertility& its Ayurvedic management including panchakarma & Agadyog.

Effects of Thyroid Hormones on Cellular Development in Human Ovarian Granulosa Tumor Cells (KGN).

Ovarian cancer is a common malignant tumor in the female reproductive system, and Granulosa cell tumor (GCT) of the ovary is a rare type of ovarian cancer, which significantly threatens women's reproductive health. It has been reported that dysregulation of thyroid hormones (THs) may be closely related to the progression and prognosis of ovarian cancer. Moreover, THs regulate phosphorylation of signal transducer and activator of transcription (STAT3) and Octamer-binding transcription factor 4 (OCT4) expression. It has been reported that STAT3 and OCT4 play important roles in cellular development and tumorigenesis. However, the mechanisms by which THs affect the development of GCT are still remained unclear. To evaluate the effect of THs on human ovarian granulosa tumor cells (KGN), cells were treated with 3,5,3' -triiodothyronine (T3). Oct4 small interfering (Oct4 siRNA) or STAT3 inhibitor C188-9 was also co-cultured with cells in some experiments, respectively. The cell viability, proliferation, and proteins content were detected by CCK-8, EdU, and Western Blotting, respectively. The results showed that T3 enhanced cell viability and proliferation. Moreover, T3 also increased the expression of thyroid hormone receptor (TR), p-STAT3, and OCT4 proteins. The effects of T3 on both p-STAT3 and OCT4 expression were blocked by TR antagonist 1-850. Meanwhile, C188-9, an inhibitor of STAT3, decreased T3-induced cellular viability, proliferation, and OCT4 expression, highlighting that p-STAT3 can regulate the expression of OCT4 and affect cellular viability, and proliferation. Furthermore, T3-induced cellular growth was reduced by Oct4 siRNA, which indicates that T3 regulates cellular development through OCT4. These findings suggest that T3 increases cellular development via OCT4, which is mediated by phosphorylation of STAT3, and TR is also involved in these processes.

Primary cervical malignant melanoma: A rare entity case report

Primary malignant melanoma of female genital tract is rare, and rarer are those arising from the cervix. Pathogenesis involving BRAF & RAS pathway whether holds true for these tumours as well is a question yet to be answered. Patients come with bleeding PV as their main complain. To reach at the diagnosis of primary malignant melanoma of cervix it is important to have clinical examination with speculum assessment along with pathological evaluation of the lesion. Case presentation: We report a case of 49/F, Para 1, living 1 (P1L1), who was postmenopausal since 13 years with complains of white discharge and bleeding per vaginum since 1 week. Per vaginal examination revealed a greysih white brown growth in the cervix involving vagina. Biopsy and immunohistochemistry showed malignant melanoma (MM). Conclusion: Clinical presentation and spread pattern of primary MM of cervix is similar to that of cervical carcinoma and clinically diagnosing as melanoma is even more difficult when more than 50% tumours are amelanotic. But early diagnosis is need of the hour as these cases have poor prognosis with no standardize treatment protocol available. The FIGO staging system has been accepted by most researchers. Reporting of such cases is pertinent so as to allow the study of this extremely rare tumour for bringing up the correct and new therapies for early treatment.

Clinicopathological correlation of three cases of metastatic carcinoma to uterine cervix: An institutional experience

Abstract Introduction/Objective Metastasis to the female genital tract presents a rare occurrence and poses significant diagnostic hurdles. The uterine cervix, although less frequently implicated, presents additional challenges for metastatic spread owing to its diminutive dimensions, limited vascular perfusion, and abundance of fibrous tissue. Clinical manifestations often include abnormal vaginal bleeding in 62–75% of cases, frequently accompanied by involvement in other anatomical sites. Accurate identification of cervical tumor activity and its primary origin holds paramount importance for precise diagnosis, therapeutic stratagem, and prognostic assessment. Methods/Case Report Here we are reporting three cases that were encountered in our institution over a 5-year period. The first patient, a 63-year-old female with a history of breast cancer, six years later exhibited metastatic breast cancer in a cervical polyp, confirmed by positivity for AE1/AE3, GATA3, ER, and negativity for TTF-1, chromogranin, synaptophysin, PAX8, inhibin, calretinin, CDX-2, CD10, desmin, smooth muscle actin, S100, and HMB-45. The second patient, diagnosed with pancreatic adenocarcinoma, two years later manifested cervical metastasis confirmed via positive staining for CK7, CDX2, and focal p63, and did not express PAX8, vimentin, ER, p16, synaptophysin, and chromogranin. The third patient, diagnosed with lung adenocarcinoma, one year later presented with a cervical mass, histologically confirmed as metastatic lung adenocarcinoma via positivity for CK7, Napsin A, and TTF1, and negativity for PAX8, p16, p40, p53, GATA3, and ER. Results (if a Case Study enter NA) N/A Conclusion Given the challenges of identifying metastasis to the cervix, thorough diagnostic evaluation should be undertaken to differentiate primary versus metastatic disease in women with a history of non-cervical malignancy.

Diffuse Large B-cell Lymphoma (DLBCL) involving the Uterine Corpus presenting with Abnormal Uterine Bleeding: A Rare Case Report

Abstract Introduction/Objective Diffuse Large B-cell Lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Lymphomas affecting the female genital system are extremely rare, accounting for about 1% of extra-nodal lymphomas, with DLBCL being the most common type. We present a rare case of uterine lymphoma presenting with abnormal uterine bleeding. Methods/Case Report A 50-year-old female presented with abnormal uterine bleeding and fatigue for the past three weeks. Laboratory work-up showed hemoglobin level of 5.5 g/dL. Pelvic ultrasound revealed thickening of the endometrium and a 1.6 cm hypoechoic uterine lesion along with multiple enlarged bilateral adnexal lymph nodes. Histological examination of the endometrial biopsy demonstrated endometrial fragments with diffuse subepithelial proliferation of large, poorly differentiated cells with round nuclear contours, finely dispersed chromatin, relatively inconspicuous nucleoli and moderate amount of cytoplasm. Many scattered mitoses and apoptotic bodies were present. Primary set of immunohistochemical stains were performed to rule out primary uterine epithelial or mesenchymal tumors. The tumor cells were negative for pan-keratin, high and low molecular weight keratins and positive for CD45. Further work-up demonstrated CD20 positivity. It was diagnosed as DLBCL with a non-germinal center, double expressor phenotype and a high Ki-67 proliferation. Fluorescence in-situ hybridization studies were negative for MYC and BCL6 gene rearrangements and IGH-BCL2 translocation. Further radiological workup revealed diffuse lymphadenopathy with multiple pulmonary and renal nodules consistent with Stage IV DLBCL. She was treated with six cycles of R-CHOP regimen, and complete metabolic response was achieved. Results (if a Case Study enter NA) NA Conclusion Uterine lymphomas are very rare and on small biopsies may histologically mimic poorly differentiated uterine malignancies such as dedifferentiated/undifferentiated carcinomas. Adding lymphoma lineage markers to poorly differentiated tumors is recommended to avoid missing such a rare entity.

Neoplasia in pet guinea pigs: a retrospective analysis of 2,474 autopsy examinations.

Neoplasia is a common disease in guinea pigs (Cavia porcellus); however, few studies have evaluated the prevalence of neoplasia in all organ systems. We retrospectively analyzed the tumor prevalence in pet guinea pigs and the frequency of metastasis in a multi-institutional study population of 2,474 autopsy cases. Tumors were found in 508 guinea pigs (prevalence: 20.5%), of which 95 cases had >1 tumor, resulting in a total of 627 tumors. The tumor prevalence increased from 1.4% in animals <0.5-y-old to 53.6% for guinea pigs >5-y-old. The most common tumor type was lymphoma or leukemia, affecting 174 guinea pigs (tumor prevalence: 7.0%). Lymphomas or leukemias were disseminated to various organs and/or lymph nodes in 146 (83.9%) cases and localized to 1 organ or 1 lymph node in 28 (16.1%) cases. Primary non-lymphoid tumors were most frequent in the female genital tract (62 of 1,235 cases, mostly uterus), respiratory system (116 of 2,474), skin including mammary gland (81 of 2,474), endocrine system (66 of 2,474, mostly thyroid gland), and alimentary tract (35 of 2,474). Tumors of the alimentary tract were dominated by gastrointestinal stromal tumors. Metastasis was detected in 42 of 453 non-lymphoid tumors (9.3%), with a surprisingly low frequency for pulmonary carcinoma and splenic hemangiosarcoma compared to other species. Our postmortem study demonstrates a high prevalence of disseminated lymphoma or leukemia in pet guinea pigs at the time of death or euthanasia. Additional studies are needed to further characterize these tumors.

Identification and Characterization of a Novel Insulin-like Receptor (LvRTK2) Involved in Regulating Growth and Glucose Metabolism of the Pacific White Shrimp Litopenaeus vannamei.

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism.

SHCBP1 promotes cisplatin resistance of ovarian cancer through AKT/mTOR/Autophagy pathway.

Ovarian cancer caused the highest cancer-related mortality among female reproductive system malignancies. Platinum-based chemotherapy is still the footstone of the chemotherapy for ovarian cancer. However, the molecular mechanisms underlying cisplatin insensitivity and resistance remain unclear. SHC SH2 domain-binding protein 1 (SHCBP1) plays critical roles in the progression and drug resistance of different types of cancer. However, the biological function of SHCBP1 in ovarian cancer progression and cisplatin resistance remains obscure. In this study, we found that SHCBP1 was upregulated in ovarian cancer and the upregulated SHCBP1 has growth-promoting effect on ovarian cancer cells. Furthermore, SHCBP1 silencing sensitize ovarian cancer cells to cisplatin (hereafter referred to as CDDP). Mechanism analysis revealed that SHCBP1 activated the Akt/mTOR pathway and further inhibited autophagy in ovarian cancer cells. Meanwhile, autophagy inhibitors combined with SHCBP1 knockdown enhances CDDP sensitivity. In addition, knockdown of SHCBP1 restricted the proliferation of tumors and increased the cisplatin sensitivity in vivo. These findings suggested that upregulated SHCBP1 promoted the proliferation and CDDP resistance of ovarian cancer. The combination of SHCBP1 inhibition and cisplatin treatment might lead to substantial progress in ovarian cancer targeted therapy.

Comparative analysis of micrometric parameters in the ovaries of adolescent, elderly and senile women

Aging is a systemic process affecting all tissues of the body. In this study, the choice of scientific interest fell on the paired gland, the key structure of the female reproductive system – the ovary.Objective: to carry out a comparative analysis of the parameters of the thickness of the cerebral and cortical layers, as well as the protein membrane of the ovaries in women in adolescence, the elderly and senile age. Materials and methods. The analysis of the results of a study of 60 women with normal pelvic dimensions and without pathology of the reproductive system organs was carried out. Group I included 28 victims of adolescent age (16-20 years old), group II consisted of 29 elderly victims (56-74 years old), group III included 27 elderly victims (75-90 years old). The thickness of the cerebral and cortical layers, as well as the albumen of both ovaries, were determined in histological samples.Results. A decrease in the thickness of the cortical and medulla and an increase in the thickness parameters of the albuminous membrane of both ovaries in the period from adolescence to old age were revealed. The thickness of the medulla of the right ovary is thinned by 3.76%, the left by 4.46%; the cortical substance of the right ovary by 29.9%, the left by 29.64% (p &lt; 0,01). The thickness of the albumen of the right ovary, on the contrary, increases by 48.23%, of the left – by 50.21% (p &lt; 0,01). From old age to senile age, there is a tendency to decrease the thickness of the cerebral and cortical matter of the ovary. The medulla is thinned by 0.95% on the right and 0.24% on the left (p &gt; 0,05), the cortical substance – by 1.5% on the right and 1.21% on the left (p &gt; 0,05). At the same time, the protein shell on the right becomes thicker by 14.08%, on the left – by 13.57% (p &lt; 0,01). Conclusion. The results obtained can become a conditional "morphological standard" for certain age norms in the diagnosis of various diseases, as well as expand the understanding of changes in the morphological picture of a woman's ovaries with age.

Therapeutic Potential of Quercetin and their Compound Against Ovarian Cancer: New Approaches &amp; Application

Ovarian cancer is an exceptionally perilous form of cancer as it develops within the female reproductive system. Finding effective therapy platforms for ovarian cancer has been difficult because to the diverse array of molecular pathways and genetic alterations involved in its development. Therefore, it is imperative to discover novel therapeutic methodologies and advance their development. Medicinal herbs possess the capacity to independently or in combination with other pharmaceuticals, effectively treat malignancies such as ovarian cancer. Quercetin possesses remarkable anti-inflammatory and anti-cancer properties, making it one among numerous natural compounds with such qualities. Quercetin has demonstrated cytotoxicity against ovarian cancer cells in both laboratory experiments (in vitro) and live animal tests (in vivo). The potential anti-cancer effects of quercetin, particularly in relation to ovarian cancer, have not been extensively studied in human trials, despite encouraging findings from laboratory and animal experiments. Hence, it seems that quercetin could potentially be utilized in clinical trials as a therapeutic agent, either on its own or in conjunction with other chemotherapeutic drugs. This article will outline the primary aspects of quercetin's anti-cancer characteristics and thereafter concentrate on its application in the treatment of ovarian cancer.

Burden of uterine cancer in China from 1990 to 2021 and 15-year projection: a systematic analysis and comparison with global levels

ObjectiveUterine cancer (UC) is one of the prevalent malignancies in the female reproductive system. Estimating the burden trends of UC is crucial for developing effective prevention strategies at the national level. However, there has been no comprehensive analysis of the UC burden in China. We focused on the evaluation of the burden trends of UC in China over the past 32 years to provide a 15-year projection, comparing it with global levels.MethodsData on incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were extracted from Global Burden of Disease (GBD) 2021 to describe the burden of UC in China. Joinpoint regression analysis was employed to describe the temporal trends of UC in China and globally over the past 32 years. A Bayesian age-period-cohort model was utilized to predict the trends of UC in the next 15 years. Spearman correlation analysis was used to compare the relationship between ASIR, ASPR, ASMR, ASDR, and SDI in UC in China and globally. Changes in ASMR and ASDR in UC caused by high BMI in China and globally from 1990 to 2021 were explored.ResultsIn 2021, the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of UC in China were 6.65, 46.52, 1.24, and 37.86 (per 100,000 population) respectively. Compared to 1990, the ASMR and ASDR decreased by 48.63% and 48.15% respectively, while the ASIR and ASPR increased by 17.79% and 37.67% respectively. Globally, the burden of UC followed a similar trend in China, with increasing ASIR and ASPR, and decreasing ASMR and ASDR, although the magnitude of increase and decrease was smaller than in China. Joinpoint regression analysis results showed an overall upward trend in ASIR and ASPR for both China and global UC, while an overall downward trend was observed in ASMR and ASDR. Age-specific analysis revealed that during the period from 1990 to 2021, the age groups with the highest incidence, prevalence, mortality, and DALYs for UC in China generally occurred at earlier ages compared to the global pattern. It is projected that over the next 15 years, the burden of UC in China will continue to increase at a higher rate than the global level. Spearman correlation analysis showed that ASIR and ASPR of UC in China and the world were significantly positively correlated with SDI (p < 0.05), and ASMR and ASDR were significantly negatively correlated with SDI (p < 0.001). High BMI is a risk factor affecting the mortality rate and DALYs of UC in both China and globally, with the increase in ASMR and ASDR due to high BMI being greater in China than globally.ConclusionThe incidence and prevalence burden of UC among Chinese and global women have shown an increasing trend over the past 32 years, while the mortality and DALYs have decreased. The projected burden of UC in China is anticipated to continue rising at a higher rate than the global level over the next 15 years. Given the large population in China, the government needs to strengthen screening and prevention strategies to mitigate the burden of UC.

Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis: A Multi-institutional Clinicopathologic and Molecular Study of Five Patients.

Clear cell adenocarcinoma (CCA) of the urinary tract is a rare malignancy and tumors involving the renal pelvis are notably sparse in the literature, with only 5 other patients reported. We present 5 patients, 4 women, and 1 man, with CCA of the renal pelvis. The age at presentation ranged from 29 to 81 years. The tumor size ranged from 4.5 to 8.0 cm. Tumors exhibited shared morphologic and immunohistochemical features with CCA of the female genital tract and those originating in the bladder and urethra, including cells with large nuclei, prominent nucleoli, nuclear hobnailing, and scant clear cytoplasm. Common immunohistochemical findings included reactivity for PAX8, CK7, HNF1β, and Napsin-A. One of the tumors arose in the background of a mixed epithelial and stromal tumor. Another tumor occurred in a renal allograft and tumor cells were positive for the BK virus, demonstrated by SV40 immunohistochemistry. All tumors were negative for TFE3 and TFEB rearrangement and lacked TERT alterations. Follow-up was limited with no recurrence in 4 patients at a maximum of 20 months follow-up and 1 patient died of an unrelated cause at 25 months of follow-up. Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.

A comprehensive analysis of CEBPA on prognosis and function in uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is one of the most common tumours of the female reproductive system. CCAAT enhancer-binding protein alpha (CEBPA) is a member of the transcription factor family involved in regulating processes such as cell proliferation, differentiation, metabolism, and the immune response. However, the role of CEBPA in UCEC has not been clarified. Here, we performed a comprehensive analysis to explore the expression level, prognostic value, immune infiltration and biological function of CEBPA in UCEC. In this study, we found that CEBPA expression was upregulated and associated with poor prognosis in UCEC patients. KEGG and GO analyses revealed that the genes positively correlated with CEBPA were enriched primarily in immune regulation and oxidative phosphorylation. Immune infiltration analysis revealed that CEBPA is strongly correlated with immune cell infiltration in UCEC. RT-qPCR indicated that CEBPA may regulate the OXPHOS level in Ishikawa cells. CCK-8, cell cycle, Transwell and scratch wound healing assays revealed that CEBPA promoted Ishikawa cell proliferation, invasion and migration. In addition, PPI and survival analyses suggested that CEBPG may be a potential target of CEBPA in UCEC. These results demonstrated that CEBPA may be a potential therapeutic target in UCEC.

Unexpected early pregnancy during myomectomy followed by successful term delivery: A case report.

Leiomyoma, also known as uterine fibroid, is a non-malignant tumor originating from the uterus's smooth muscles. It is the most common benign tumor in the female genital tract, exhibiting varying size and form that can distort the uterus's shape. Uterine fibroids affect 2.7-10.7% of pregnant women and can lead to increased risks during pregnancy, such as miscarriage, placental abruption, preterm labor, and fetal malpresentation. Myomectomy is a surgical intervention for uterine fibroids, but it has drawbacks, including hemorrhage, fever, infection, ureter ligation, adhesive disorders, and unplanned hysterectomy. In this case report, we present a 32-yr-old woman with a large leiomyoma who underwent laparotomy myomectomy due to abdominal pain and heavy menstrual bleeding. 4 wk after the myomectomy, she was referred to the Obstetric Clinic of Ayatollah Taleghani hospital, Tehran, Iran complaining of delayed menstruation. Her beta-human chorionic gonadotropin test was positive. Ultrasound revealed a fetus with an estimated gestational age of 6 wk and 4 days. The pregnancy continued with no complications. At 38 wk of gestation, she underwent a cesarean section and delivered a healthy newborn. This case report supports previous publications that have demonstrated the safety of myomectomy during pregnancy.

Effects of Polyvinyl Chloride Microplastics on the Reproductive System, Intestinal Structure, and Microflora in Male and Female Mice

The pervasive use of plastics in numerous industrial sectors has resulted in the circulation of microplastics across diverse ecosystems and food chains, giving rise to mounting concerns regarding their potential adverse impacts on biological systems and the environment. The objective of this experiment was to investigate the distinct effects of microplastic-polyvinyl chloride (PVC) exposure on the reproductive system, intestinal tissue structure, and intestinal microbial flora of both male and female mice. A total of 24 4-week-old Kunming mice were randomly assigned to one of four groups: male control group (CM), female control group (CF), male PVC test group (PVCM), and female PVC test group (PVCF) (n = 6). The findings revealed that in terms of the reproductive system, the PVCM group exhibited an impaired testicular structure with an irregular arrangement and a significant reduction in spermatogonia, spermatocytes, and spermatozoa within the seminiferous tubules (p &lt; 0.01). The PVCF group exhibited a notable decrease in ovarian follicles (p &lt; 0.01), accompanied by a reduction in uterus volume, fallopian tube volume, and muscle layer thickness, all of which also decreased significantly (p &lt; 0.01). In comparison to the control groups, exposure to PVC resulted in a reduction in the width and height of the intestinal villi, accompanied by an increase in crypt depth. This led to a significant alteration in the ratio of villus height to crypt depth (V/C) (p &lt; 0.01). Moreover, a reduction in microbial species diversity was observed within both the PVCM and PVCF groups; additionally, it was accompanied by contrasting changes in relative abundance and functional gene profiles among the major intestinal flora constituents. In summary, the findings indicate that PVC induces damage to both male and female mice reproductive and digestive systems, further exhibiting notable sex-dependent effects on mouse intestinal microflora composition, which correlates significantly with its impact on reproductive organs.

Prenatal phthalate exposure and pubertal development in 16-year-old daughters: reproductive hormones and number of ovarian follicles.

Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later. Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction. This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother-Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002. A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females. In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration. Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size was limited. Our results support the need for further research into possible adverse effects of environmental chemicals during foetal development of the female reproductive system. The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065). No conflicts of interest are declared. N/A.

The cGAS-STING pathway and female reproductive system diseases.

The cGAS-STING pathway has become a crucial role in the detection of cytosolic DNA and the initiation of immune responses. The cGAS-STING pathway not only mediates protective immune defense against various DNA-containing pathogens but also detects tumor-derived DNA to generate intrinsic anti-tumor immunity. However, abnormal activation of the cGAS-STING pathway by self-DNA can also lead to autoimmune diseases and inflammatory disorders. This article reviews the mechanisms and functions of the cGAS-STING pathway, as well as the latest research progress in female reproductive-related diseases. We focus on the regulatory mechanisms and roles of this pathway in common female reproductive disorders, discuss the clinical potential of the cGAS-STING pathway as biomarkers and therapeutic agents for female reproductive diseases, as well as the research controversies, technical issues, and biological knowledge gaps that need to be resolved. Furthermore, we provide new ideas for the treatment and prevention of these diseases.

Targeting KRAS in gynecological malignancies.

Cervical, endometrial, and ovarian cancers stand prominently as the leading gynecological malignancies of the female reproductive system. The conventional therapeutic modalities for gynecological malignancies have predominantly encompassed surgery, chemotherapy, and radiotherapy. However, efficacy of these approaches remains limited in cases of relapse or drug resistance. KRAS is one of the most frequently mutated oncogenes in human cancers. The KRAS gene encodes a small guanosine triphosphatase protein that acts as a molecular switch for crucial intracellular signaling pathways. KRAS mutations are deeply involved in the occurrence and development of gynecological malignancies. The present review aims to expound upon the role of oncogenic KRAS as a biomarker, elucidating various therapeutic approaches under investigation targeting the KRAS pathway in gynecological tumors.

8795 Impact of Retinoic Acid Receptor Alpha Conditional Knockout on Ovarian Follicle Development in the Mouse

Abstract Disclosure: Z. Bogin: None. A. Keisker: None. A. Urbanowski: None. C. White: None. J.L. Kipp: None. The ovaries are the primary endocrine and reproductive organs in females. The ovarian follicle is the basic structural and functional unit of the ovary. When there is abnormal development in ovarian follicles, infertility and reproductive diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and ovarian cancers may occur. Retinoic acid (RA), a biologically active derivative of vitamin A, is a signaling molecule that plays a vital role in various physiological processes, including embryonic development, tissue differentiation, and reproduction. We have shown that RA stimulates granulosa cell proliferation through a cell signaling cascade involving Retinoic Acid Receptors (RARs), which have three isoforms alpha, beta, and gamma. In this study, we characterized a new retinoic acid receptor alpha conditional knockout (RARA cKO) mouse model with RARA deleted in granulosa cells during embryonic development. The body weight and uterus weight of the RARA cKO mice were decreased at week 7 but returned to normal at week 15 and 12 months. The animals were either sub-fertile or infertile with phenotypic evidence of POF. In addition, a variety of ovarian pathologies were observed, including the presence of hemosiderin, increased cyst formation, and abnormal follicle counts. Overall, this study provides evidence of the involvement of retinoic acid signaling, mediated by RARA, in ovarian development and fertility. This study will help to better understand the prevention and treatment of ovarian diseases. Presentation: 6/2/2024