bluuebunny/crossref_metadata_2025_split huggingface dataset:
DHT Differentially Regulates T Helper Cell Related Cytokines and MicroRNAs In Visceral and Subcutaneous Adipose Tissue of Female Mice
Authors: Kothmann Kadden H , Kay Matthew , Romney Sherdina E , Acebo Sarah , Reyna Andrea J , Choudhury Mahua , Rutkowski Joseph M , Newell-Fugate Annie E 
Published: May 2021

Abstract
Hyperandrogenemic, insulin resistant polycystic ovarian syndrome (PCOS) patients often have low-grade inflammation due to elevated circulating pro-inflammatory markers. As up to 60% of PCOS patients are obese, whether this low-grade inflammatory state is due to increased adiposity or other factors such as hyperandrogenemia is unknown. Moreover, the systemic inflammation of obesity is correlated with recruitment of pro-inflammatory immune cell populations to WAT. We hypothesized that short-term administration of the potent androgen, dihydrotestosterone (DHT), to female mice would increase pro-inflammatory cytokines and microRNA (miR) associated with pro-inflammatory cytokines and immune cell populations in WAT. Sexually mature, normally-cycling female C57/Bl6 mice received a daily sc injection of oil (0 g; n=7) or DHT (27.5 g; n=7) beginning at estrus. Females had vaginal cytology daily. After three cycles or 12-16 days if mice became acyclic, mice were euthanized for collection of blood and WAT. Serum was analyzed for DHT and testosterone (TEST) by LC-MS/MS. TaqManTM Array Mouse Immune Response PCR assays (Thermofisher Scientific) were used to measure transcript expression levels in vWAT and scWAT. Ingenuity Pathway Analysis (IPA) (Qiagen) was used to analyze relationships between different transcript levels in each treatment group for each tissue. DHT mice had 17 fold higher serum DHT levels than oil mice but there was no difference in serum TEST between treatment groups. DHT mice had a significantly longer estrous cycle length then oil mice. Short-term administration of DHT significantly upregulated 23% (21 of 92) of transcripts in scWAT and downregulated 49% (45 of 92) of transcripts in vWAT. The top four canonical pathways identified by IPA in WAT were: T helper cell 1 (Th1), Th1 & T helper 2 activation, Helper T cell differentiation, and Altered B & T cell signaling. Based on the Th1 pathway derived from IPA, the following miRs (both -3p and 5p) downstream of Th1 activation targets were selected for qPCR in vWAT and scWAT: miR21, miR146a, miR29a, and miR155. Interestingly, miR-21a-5p, miR-146a-5p, and miR-155-5p were significantly upregulated in scWAT from DHT mice. No miRs were different between treatment groups in vWAT. We demonstrate for the first time that short-term DHT administration may cause immunosuppression in vWAT and inflammation, possibly mediated by miRs, in scWAT of female mice.
Prolactin Receptor (PRLR) Isoform Expression in the Murine Oviduct
Authors: Radecki Kelly C , Lorenson Mary Y , Walker Ameae M 
Published: May 2021

Abstract
The most common and most deadly form of “ovarian”cancer is High-Grade Serous Carcinoma (HGSC), now appreciated to arise from epithelial cells of the fallopian tube/oviduct. The serum analyte with the greatest specificity and sensitivity that correlates with the presence or absence of HGSC is prolactin (PRL). However, unknown is whether elevated PRL initiates disease or is the result of disease, although once cancer is present,it is clear that PRL promotes disease. In order to examine the potential for disease initiation in normal animals, it was first important to determine which cells in the mouse oviduct respond to PRL. In many cell types, the long form of the Prlr mediates increased survival, proliferation and migration, whereas the short forms have the opposite effect. After establishing equivalent efficiencies of primers for the long form (LF) and 3 short forms (SF1-3) of the murine Prlr and the endogenous control gene, Gapdh, the mRNA expression profiles of these forms of the receptor were followed by RT-qPCR as a function of stage of the estrous cycle (proestrus, estrus, metestrus, diestrus - determined by vaginal cytology) and region of the oviduct (isthmus, ampulla and fimbria). Expression of SF1 was not detected. SF2 was essentially consistently expressed throughout the oviduct and at all stages of the estrous cycle. By contrast, the ratio of LF to SF3 varied by region of the tube, with more SF3 towards the fimbria and more LF towards the isthmus. The epithelium of the oviduct is primarily composed of multi-ciliated cells and secretory cells, with more ciliated cells towards the fimbria and more secretory cells towards the isthmus. The RT-qPCR results therefore suggested the possibility that a greater proportion of LF Prlr was present on secretory cells and a greater proportion of SF3 Prlr on ciliated cells. Using antibodies raised against intracellular peptide regions specificto the LF (aa 309-325) and SF3 (aa 281-296), both receptor isoforms were localized by immunofluorescence to apical regions of both epithelial cell types,but the presence of receptors on cilia (clearly demonstrated by 3Dreconstruction and rotation) complicated analysis of relative fluorescence by microscopy. Only the LF Prlr signals via Stat5 and so it was anticipated thatStat5 activation could serve as a substitute marker of the relative presence ofLF Prlr. Following in vivo intraperitoneal injection of PRL (5μg/g, 30 min),activated Stat5 was localized to epithelial cells at the base of, and in between, mucosal folds, thereby suggesting a further regionality to receptor distribution. For the fimbrial region only, which is where HGSC is thought to arise, expression of both the LF and SF3 Prlr changed as a function of the stage of the estrous cycle, with highest mRNA expression at diestrus/proestrus. Ongoing work includes flow cytometry of epithelial subpopulations and spatialanalysis of gene expression.
Heterozygous Eif4nif1 Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype
Authors: Moriwaki Mika , Welt Corrine Kolka 
Published: May 2021

Abstract
We identified a stop-gain mutation in eIF4ENIF1 in a family in which multiple women developed primary ovarian insufficiency (POI) at approximately age 30 years. We hypothesized that the same mutation in a mouse model would replicate POI. Methods: The Eif4enif1 C57/Bl6 transgenic mouse model contains a floxed exon 10-19 cassette and a conditional knock-in cassette containing exon 10 with the c.1286C&gt;G stop-gain mutation causing familial POI and WT exons 11-19 (Eif4enif1WT/flx). The hybrid offspring of CMV-Cre mice with Eif4enif1WT/flx mice were designated Eif4enif1WT/Δ for simplicity. Follicles were counted in fixed H&E stained ovaries from mice age days 1-5 (primordial and primary follicles), day 10, day 22 (first wave of growing follicles from small preantral to small antral follicles), week 20 (peak fertility), then every 2 months from 10 months to 26 months (follicle exhaustion). Litter frequency, pup number and genotype were recorded. Serum FSH levels were measured by the University of Virginia Ligand Assay and Analysis Core. Results: The heterozygotes have no outward or internal phenotypic differences compared to WT (Eif4enif1WT/flx), with the exception of reproductive organs in females and males. A subset of female heterozygotes (Eif4enif1WT/Δ) had no litters for 20 weeks (2 of 18; 11%). In those with litters, the average length of time between litters was not different but the final litter was earlier (5.6±2.7 vs. 10.5±0.7 months; p=0.02). Heterozygous breeding pair (Eif4enif1WT/Δx Eif4enif1WT/Δ) litter size was 60% of WT litter size (3.9±2.3 vs. 7.2±2.1 pups/litter; 0&lt;0.001). The genotypes were 35% Eif4enif1WT/flx and 65% Eif4enif1WT/Δ, with no homozygotes. The number of follicles in ovaries from Eif4enif1WT/Δ mice was lower starting at the primordial (499±290 vs. 1445±381) and primary follicle stage (1069±346 vs. 1450±193) on day 10 (p&lt;0.05). The preantral follicle number was lower starting on day 21 (213±86 vs. 522±227; p&lt;0.01) and the antral follicle count was lower starting on week 20 (78±38 vs. 119±18; p&lt;0.01). The FSH level in 12-month old mice during estrus was higher in a heterozygote compared to WT (25.0 vs. 12.1 ng/mL). Conclusions: Heterozygous Eif4enif1 stop-gain mutants have follicle loss documented by day 10, decreased pup number with no homozygotes, earlier end of reproductive function and elevated FSH levels. These mice replicate the POI phenotype in women. eIF4ENIF1 regulates protein translation by binding and storing eIF4E bound mRNA. Therefore, the unique mouse model provides a platform to study temporal and spatial regulation of protein translation across oocyte and embryo development in mammals. Further studies will determine whether follicle loss results from premature protein translation in oocytes.
A Case of Hyperreactio Luteinalis Complicated With Biochemical Hyperandrogenism, Symptomatic Hyperthyroidism and Preeclampsia
Authors: Wong K Y , Mak M W H , Lee K M , Lee K F 
Published: May 2021

Abstract
Background: Hyperreactio luteinalis (HL) describes the development of multiple large ovarian cysts during pregnancy, which regress post-partum. We report a case of HL complicated with preeclampsia, biochemical hyperandrogenism and hyperthyroidism. Clinical Case: A 31-year-old non-obese Chinese woman presented at 14-week gestation for lower abdominal pain. USG showed a single fetus, multiple ovarian cysts with largest measured 39.5ml. She complained of hand tremor, palpitation but no vomiting. She had no goiter, orbitopathy or family history of thyroid disease. fT4 was 23.1pmol/L (normal: 9.8-19.8pmol/L) and TSH was &lt;0.01mIU/L. Anti-TG, anti-TPO and anti-TSHR antibodies were negative. She had history of silent miscarriage at 6-week gestation in her first pregnancy 2 years ago, USG showed normal ovaries at that time. Carbimazole was started at 16-week gestation for fT4 26.6pmol/L (normal: 9.4-18.5pmol/L). The largest ovarian cyst increased to 130ml at 19-week gestation. Serum β-hCG was 251926IU/L (normal: 4060-165400IU/L). HL with hCG-mediated hyperthyroidism was suspected. Serum total testosterone was 22.9nmol/L (normal: 2.2-10.7nmol/L) and serum androstenedione was 70.5nmol/L (normal: 0.28-9.81nmol/L). Ferriham Gallwey score was 4. fT4 fell to 13.8pmol/L (normal: 8.8-17.0pmol/L) but TSH remained suppressed. Carbimazole was stopped at 22-week gestation with no rebound in fT4 level. She developed preeclampsia and GDM at 27-week gestation. IUGR was evident despite decreasing β-hCG level and ovarian cyst shrinkage. She had emergency LSCS for severe preeclampsia at 33-week gestation. A 1510g female baby with normal genitalia was delivered. Placenta pathology was normal. 2 days after delivery, β-hCG fell to 7081IU/L; fT4 was 9.9pmol/L (normal: 9-19pmol/L) and TSH was 0.25mIU/L (normal: 0.35-4.5mIU/L). Clinical Lessons: 1) hCG stimulates growth of ovarian stroma and androgen secretion, results in virilization in 30% of HL patients. However, only 5% of patients had hyperthyroidism. LH and hCG are structurally similar and bind to the same receptor. In contrast, hCG is a weak agonist of TSH receptor: a hCG level of more than 100000IU/L is required to cause clinical thyrotoxicosis. Since 30% of HL patients have normal hCG level, this may explain the lower incidence of hyperthyroidism than hyperandrogenism. 2) Degree of maternal virilization does not correlate with testosterone level. Study by Condic et al. found significant overlap of testosterone levels in women with (13.7-197.5nmol/l) and without (6.2-37.3nmol/l) virilization. Genetic polymorphism of androgen receptor may account for the different clinical manifestation. Fetal virilization is rare, due to protective role of placental aromatase. 3) Elevated hCG in apparently “normal” singleton pregnancy may be due to poor placentation in early gestation and is a risk factor for preeclampsia and IUGR in HL patients.
An Unusual Cause of Primary Amenorrhea
Authors: Marenych Nadiia , Patel Sabah , Gilden Janice L 
Published: May 2021

Abstract
Background: Müllerian agenesis is the most common cause of primary amenorrhea in patients with typical thelarche and adrenarche. Most of the time, this diagnosis is made at the age of 10-13 years. Clinical Case: We present a case of a 18 year-old Vietnamese female who was referred to the endocrine clinic for primary amenorrhea. She stated that pubic hair developed at age 15 years. Patient is sexually active and uses condoms. She has 10 siblings (7 sisters, 3 brothers), 6 older sisters with menarche at ages 12-16 and a younger sister of 10 years old who has not yet had menarche. In addition, her older sister has 3 biological children and there was no reported infertility in her family. She stated that a pelvic ultrasound had been done at age of 17 years that showed no uterus. Oral contraceptives had been previously trialed and failed to induce withdrawal bleeding. HT 157.48 cm, WT 55.34 kg. The patient had a normal female phenotype with normal bilateral breast development, and no hirsutism. She was not concerned with this issue, which questioned her personality and coping skills. Laboratory testing-cortisol 13.0 ug/dL (5.3- 2.5), ACTH 29 pg/mL (0-47), estradiol 46.04 pg/mL), total testosterone 39 ng/dL (2-45), free testosterone 4.2 pg/mL (0.1-6.4), TSH 1.80 uIU/mL (0.358- .74), free T4 0.99 ng/dL(0.76- .46), FSH 4.4 mIU/mL (Follicular Phase:2.3 - 12.6, Midcycle Peak:5.2-17.5 mIU/mL, Luteal Phase:1.7-12.9 mIU/mL), Progesterone &lt;0.5 ng/mL (follicular -less than 0.8 ng/ml, luteal=4.1- 3.7 ng/ml, mid-luteal= 4.5-25.2 ng/ml), LH 3.7 mIU/mL (follicular phase = 1.9-26.2 mIU/mL, Midcycle = 22.8 - 6.1 mIU/mL, Luteal phase = 0.6-16.6 mIU/mL). Transvaginal ultrasound-uterus not visualized; ovaries were unremarkable. DXA scan-normal Z scores. She refused to have a karyotype analysis. Differential diagnoses included müllerian agenesis, 5-alpha-reductase deficiency and complete androgen insensitivity syndrome. Unfortunately, our patient declined karyotype testing. Based on clinical presentation, which showed normal female genitalia, absence of uterus and normal laboratory finding, the most likely diagnosis was müllerian agenesis (Mayesr-Rokitansky-Kuster-Hauser syndrome). This syndrome has an incidence of 1/4,500-5,000 females and is caused is caused by embryologic underdevelopment of the müllerian duct, with resultant agenesis or atresia of the vagina, uterus, or both. Patients with müllerian agenesis usually are identified when they are evaluated for primary amenorrhea with otherwise typical growth and pubertal development, as in our patient. Psychosocial and genetic counseling, as well as offering options for pregnancy are important. In addition, certain personality traits, such as higher neuroticism, depression, and decreased coping styles may be observed. References: Obstetrics and Gynecology, Müllerian agenesis: Diagnosis, management, and treatment. Vol.131, NO.1, January 2018
Sertoliform Endometrioid Carcinomas of the Right Ovary
Authors: Alhubail Humoud , Aljenaee Khaled , Hajji Sulaiman 
Published: May 2021

Abstract
Background: Endometrioid carcinomas of the ovary are a sub-type of epithelial ovarian tumors. The vast majority are malignant and invasive. On imaging, they are usually characterized as complex nonspecific solid-cystic masses and found associated with endometriosis. However, endometrioid carcinoma of ovary resembling sex cord-stromal tumor is a rare variant of endometrioid adenocarcinoma that focally looks like a sex cord-stromal tumor with sertoli, leydig, or granulosa cells. Sertoliform endometrioid carcinoma of the ovary (SEC) is one variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs).
Clinical Case: A 47 year old, premenopausal female, presented with rapid growing hirsutism, frontal hair loss, abdominal distension and constipation for less than one year. On clinical examination modified Ferriman-Gallwey (mFG) score was 17/36. Abdominal examination showed a palpable mass in lower abdomen, 25cm in size, rounded, and hard in nature. CT abdomen and pelvis revealed large pelvic abdominal mass (21x20.5x17 cm) with cystic and basal soft tissue components related to right ovary. Preoperatively laboratory investigations showed FSH 9.96 mIU/mL, LH 15.4, Estradiol (E2) 94.7 pg/ml, raised total testosterone 4.38 nmol/l, normal SHBG 34 nmol/l and normal DHEA-S 161 microg/dl.
Total abdominal hysterectomy and bilateral salpingo-oophorectomy was done, in which the right ovary was seen to be replaced by a solid cystic tumor with ruptured capsule. Grossly, the right ovary was enlarged measuring 9.5 cm × 8 cm × 4.8 cm. Microscopy showed round to solid tubules lined by pseudostratified columnar epithelium with elongated nuclei resembling sertoli tumor-like pattern along with conventional endometrioid tumor. A histopathological diagnosis of SEC of right ovary was made. Immunohistochemistry showed tumor cells strongly immunoreactive for epithelial membrane antigen (EMA), cytokeratin (CK) but negative for inhibin, thus confirming the diagnosis of SEC of right ovary.
Conclusion: SEC is extremely rare variant of endometrioid carcinomas and tend to present at an earlier stage as compared with most endometrioid carcinomas of the ovary. Recognition of SEC in virilizing patients is important as it is a well-differentiated, low-grade malignancy that displays a good prognosis when confined to the ovary.
Body Composition of Transgender Women After Long-Term Hormone Therapy - a Cross-Sectional Study
Authors: Alvares Leonardo A M , Santos Lívia M , Santos Marcelo R , Souza Francis R , Almeida Victor P , Mendonca Berenice Bilharinho , Costa Elaine Maria Frade , Alves Maria-Janieire N Nunes , Domenice Sorahia 
Published: May 2021

Abstract
Introduction: Few studies of transgender women (TW) body composition (BC) in long-term gender-affirming hormone therapy (GAHT) have been reported. Objective: To evaluate BC parameters of TW in long-term GAHT. Methods: A cross-sectional study was carried out with 8 TW (average age of 34.0 yo ±4.8), 8 cisgender men (CM) and 8 cisgender women (CW) matched to age and body mass index (BMI). All TW were non-gonadectomized subjects and were in estrogen [(E); transdermal estradiol (n=2), oral estradiol (n=3) and conjugated estrogen (n=3)], plus cyproterone acetate (CA) (n=8) therapy in an average time of 15.6 ±8.7 years of treatment. Total testosterone (ng/dL) levels of TW, CW and CM were 83,5 (range 12,0-637,0), 20,5 (range 12,0-41,0) and 480,5 (range 264,0-843,0) at the time of the study, respectively. BC was assessed by InBody 720. Percentage of fat mass (%FM), skeletal muscle mass (SMM) were evaluated. Baumgartner Index was calculated. Results: Regards %FM, that of TW was lower than CW (29,59 ±7,56 vs 32,9 ±3,99; p=0,5394) and higher than CM (23,58 ± 6,44; p=0.1512). SMM of TW was 33.6% higher than that of CW (p&lt;0.001) and 14,7% lower than that of CM (p=0,014). Baumgartner Index of CM group was 17.7% higher than TW group (p=0,001), which presented rates 20.3% higher than the CW (0,002). Discussion: BC changes in the first two years of GAHT in TW were consistent with loss of lean mass and gained fat mass associated with an increase of body weight. This profile was identified in adults and youth transgender after short-term hormone therapy. Conclusion: Our data shown a similar profile of short-term treatment, with a body composition intermediate between BMI-matched cisgender males and females. However, unlike young TW undergoing short-term GAHT, the parameters of BC in the TW using estrogens plus cyproterone acetate in the long term did not present %FM statistically different from CW and CM, in contrast to the lean mass that maintained significant differences in the long term.
Management of Recurrent Deep Vein Thrombosis in a Transgender Woman
Authors: Oguz Seda Hanife , Buyukasik Yahya , Yildiz Bulent O 
Published: May 2021

Abstract
Background: Transgender people using hormone treatment require lifelong medical care. Although cross-sex hormone treatment (CSHT) is usually considered safe, serious adverse events may occur. Here we report a case of deep vein thrombosis associated with estradiol treatment in an otherwise healthy young transgender woman. Case Presentation: A 21-year-old transgender woman using CSHT applied to our outpatient clinic with the complaint of painful swelling in her left leg. She was diagnosed with deep vein thrombosis (DVT) in the same leg one year earlier when she was admitted to the emergency room of another hospital with similar symptoms, and was given warfarin treatment for 3 months which has improved the symptoms. Three months after cessation of warfarin, symptoms re-occurred, but she was only able to apply to our clinic after another 3 months due to COVID-19 pandemic. Physical examination was unremarkable except asymmetrical swelling in the left leg. She has been receiving oral estradiol 6 mg/day and spironolactone 200 mg/day for 2 years. She denied taking estradiol in higher doses than recommended. She did not have any predisposing factors for DVT including obesity, immobilization and smoking. She had no prior history of venous thromboembolic events (VTE). Family history was also negative for thrombophilia except her uncle was diagnosed with ischemic cerebrovascular event at the age of 60. Lower extremity venous doppler ultrasonography revealed a thrombus in the left popliteal vein that caused total obstruction of blood flow to the distal. Plasma levels of d-dimer and fibrinogen were 0.35 mg/L and 262 mg/dL, respectively. Serum levels of sex hormones were estradiol: 204 pg/mL, total testosterone: 22.4 ng/dL, FSH: 0.22 mIU/mL, LH: 1.5 mIU/mL. Thrombophilia panel revealed a homozygous mutation in MTHFR (1296), and heterozygous mutations in both Factor V Leiden and plasma activator inhibitor (4G/5G). She was given enoxaparin in addition to warfarin until INR was elevated up to desired levels. Oral estradiol treatment was switched to transdermal route. Life-long anticoagulant treatment was suggested since the thrombotic event was triggered by estradiol treatment which will be continued. Conclusions: Limited data are available on incidence and management of VTE associated with estradiol treatment in male-to-female individuals. As in general population, routine screening for thrombophilia is not recommended in transgender women prior to the initiation of CSHT if no personal or family history of VTE is present. Even in the absence of predisposing factors, life-long anticoagulant therapy may be considered since the VTE-provoking estradiol treatment will be continued. Switching the route of estradiol treatment from oral to transdermal may be beneficial.