The Important Role of Sex-Related Sox Family Genes in the Sex Reversal of the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

The Chinese soft-shelled turtle Pelodiscus sinensis shows obvious sexual dimorphism. The economic and nutrition value of male individuals are significantly higher than those of female individuals. Pseudo-females which are base to all-male breeding have been obtained by estrogen induction, while the gene function and molecular mechanism of sex reversal remain unclear in P. sinensis. Here, comparative transcriptome analyses of female, male, and pseudo-female gonads were performed, and 14,430 genes differentially expressed were identified in the pairwise comparison of three groups. GO and KEGG analyses were performed on the differentially expressed genes (DEGs), which mainly concentrated on steroid hormone synthesis. Furthermore, the results of gonadal transcriptome analysis revealed that 10 sex-related sox genes were differentially expressed in males vs. female, male vs. pseudo-female, and female vs. pseudo-female. Through the differential expression analysis of these 10 sox genes in mature gonads, six sox genes related to sex reversal were further screened. The molecular mechanism of the six sox genes in the embryo were analyzed during sex reversal after E2 treatment. In mature gonads, some sox family genes, such as sox9sox12, and sox30 were highly expressed in the testis, while sox1, sox3, sox6, sox11, and sox17 were lowly expressed. In the male embryos, exogenous estrogen can activate the expression of sox3 and inhibit the expression of sox8, sox9, and sox11. In summary, sox3 may have a role in the process of sex reversal from male to pseudo-female, when sox8 and sox9 are inhibited. Sox family genes affect both female and male pathways in the process of sex reversal, which provides a new insight for the all-male breeding of the Chinese soft-shelled turtle.

Breast Cancer as a Possible Complication of Some Types of Covid.19 Vaccines

Quick development of COVID.19 vaccines, trigger a big question about validity of clinical trials conducted on it. We observed several short-term consequences of this artificial method of immunization, but no one knows the long-term outcomes of it, I regarded that exogenous estrogen constituent of it as probable cause of breast cancer, specifically among older women.

Hypothesis: Breast Cancer as a Possible Complication of Some Types of COVID.19 Vaccines

Quick development of COVID.19 vaccines, trigger a big question about validity of clinical trials conducted on it. We observed several short-term consequences of this artificial method of immunization, but no one knows the long-term outcomes of it, I regarded that exogenous estrogen constituent of it as probable cause of breast cancer, specifically among older women.

The Impact of Exogenous Estrogen Exposure on the Characteristics and Outcome of Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer

<b><i>Introduction:</i></b> The impact of exogenous estrogen exposure on breast cancer characteristics and outcomes is not well described. We aimed to investigate the effect of prior treatment with oral contraceptives (OCT), hormone replacement therapy (HRT), and fertility treatments on early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. <b><i>Methods:</i></b> This is a single-center retrospective cohort study comprising all women with ER-positive, HER2-negative, early breast cancer whose tumors were sent to Oncotype DX analysis between 2005 and 2012. Data on prior exposures to OCT, HRT, and fertility treatments were collected. The impact of these exposures on prespecified histopathological features was assessed including tumor size, nodal status, intensity of the hormonal receptors, grade, Oncotype recurrence score, Ki67, and lymphovascular and perineural invasion. The impact of these exposures on disease-free survival (DFS) and overall survival (OS) was also evaluated. <b><i>Results:</i></b> A total of 620 women were included, of which 19% had prior exposure to OCT, 30% to HRT, and 11% to fertility treatments. OCT use was associated with smaller (≤1 cm) tumors (<i>p</i> = 0.023) and were less likely to have grade 3 disease (<i>p</i> = 0.049). No other associations were found between exogenous estrogen exposure and tumor characteristics. Median follow-up was 10.4 years. Ten-year DFS was 85.7%, and it was not influenced by exogenous exposure. Ten-year OS was 90.2%, and OCT was associated with improved OS in univariate analysis (HR = 0.31, 95% CI: 0.11–0.85), but this difference did not remain significant in multivariate analysis (<i>p</i> = 0.275). <b><i>Conclusion:</i></b> The impact of exogenous estrogen exposure on ER-positive, HER2-negative early breast cancer characteristics is limited. In the long term, none of the evaluated exposures had negative effect on DFS and OS.

Uptake of exogenous estrogen as a differential diagnosis of ovarian-remnant-syndrome in a bitch: a case report

Background Clinical signs of heat in bitches that have been previously spayed are often associated with the presence of ovarian remnant syndrome. The inclusion of exogenous estrogens as a differential diagnosis in this regard is often ignored and may lead to misinterpretation of the case. Case presentation Herein, we report a case of exogenous estrogen exposure over several months to a 6.5-year-old spayed crossbred bitch, weighing 8.4 kg. The bitch presented in the clinic because of suspected ovarian remnant syndrome. Castration was performed within the first 6 months after birth. Important endocrine parameters measured at the first appointment were Anti-Müllerian hormone (< 0.01 ng/mL), progesterone (0.36 ng/mL), estradiol-17ß (20.7 pg/mL), and luteinizing hormone (< 0.1 ng/mL). After an extensive conversation with the owner, it was revealed that she was using an estrogen spray because of severe menopausal symptoms. After the owner stopped using this spray, the symptoms of the bitch disappeared. Conclusion Therefore, the uptake of estrogens should be a differential diagnosis for symptoms of the ovarian remnant syndrome. A detailed anamnesis is crucial to identify the source of estrogen in the environment of the affected bitch.

Functional roles of female sex hormones and their nuclear receptors in cervical cancer

There has been little progress for several decades in modalities to treat cervical cancer. While the cervix is a hormone-sensitive tissue, physiologic roles of estrogen receptor α (ERα), progesterone receptor (PR), and their ligands in this tissue are poorly understood. It has hampered critical assessments of data in early epidemiologic and clinical studies for cervical cancer. Experimental evidence obtained from studies using mouse models has provided new insights into the molecular mechanism of ERα and PR in cervical cancer. In a mouse model expressing human papillomavirus (HPV) oncogenes, exogenous estrogen promotes cervical cancer through stromal ERα. In the same mouse model, genetic ablation of PR promotes cervical carcinogenesis without exogenous estrogen. Medroxyprogesterone acetate, a PR-activating drug, regresses cervical cancer in the mouse model. These results support that ERα and PR play opposite roles in cervical cancer. They further support that ERα inhibition and PR activation may be translated into valuable treatment for a subset of cervical cancers.

Insilico Analysis of the Potential Phytoestrogens of Selected Alkaloid from ‎Soursop (Annona muricata) Leaves

Estrogen is an important hormone in the female reproductive system, as well as other systems in men and women. The decrease of estrogen levels mainly occurs in the menopause phase. The decrease of estrogen is one indication of the presence of various diseases such as cardiovascular disease. Decreased levels of estrogen can be treated by administering exogenous estrogen such as Estradiol-17β. However, long-term administration of estradiol plays an important role in tumor cell growth. Phytoestrogens are plant-basedpolyphenolic compounds that have a structure and biological activity similar to the estrogen. Phytoestrogens can be derived from alkaloid compounds, one of which is found in the soursop (Annona muricata) leaves. The purpose of this study was to analysis the potential phytoestrogens of selected alkaloid in the A. muricata leaves. The analysis was carried out using the insilico approach using molecular docking methods, pharmacokinetic analysis and druglikeness. The molecular docking results showed that the ligands could bind to the receptors on the specific binding site with the lowest binding affinity value approaching the control ligands, namely the Anonaine compound of -8.6 kcal / mol, followed by Xylopine compound of -7.8 kcal / mol and Annonamine of -7.0 kcal / mol. The results of pharmacokinetic and druglikeness showed that all ligand compounds have a good ability to be absorbed in the gastrointestine and have a good bioavalaibility as an oral drug.

Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.

No Venous Thromboembolism Increase Among Transgender Female Patients Remaining on Estrogen for Gender-Affirming Surgery

Background Both surgery and exogenous estrogen use are associated with increased risk of venous thromboembolism (VTE). However, it is not known whether estrogen hormone therapy (HT) exacerbates the surgery-associated risk among transgender and gender nonbinary (TGNB) individuals. The lack of published data has contributed to heterogeneity in perioperative protocols regarding estrogen HT administration for TGNB patients undergoing gender-affirming surgery. Methods A single-center retrospective chart review was performed on all TGNB patients who underwent gender-affirming surgery between November 2015 and August 2019. Surgery type, preoperative HT regimen, perioperative HT regimen, VTE prophylaxis management, outcomes, and demographic data were recorded. Results A total of 919 TGNB patients underwent 1858 surgical procedures representing 1396 unique cases, of which 407 cases were transfeminine patients undergoing primary vaginoplasty. Of the latter, 190 cases were performed with estrogen suspended for 1 week prior to surgery, and 212 cases were performed with HT continued throughout. Of all cases, 1 patient presented with VTE, from the cohort of transfeminine patients whose estrogen HT was suspended prior to surgery. No VTE events were noted among those who continued HT. Mean postoperative follow-up was 285 days. Conclusions Perioperative VTE was not a significant risk in a large, homogenously treated cohort of TGNB patients independent of whether HT was suspended or not prior to surgery.