Müllerian Duct Research Articles

Mayer–Rokitansky–Kuster–Hauser Syndrome Type II with Mullerian Duct Aplasia–Renal Dysplasia–Cervical Somite Anomalies Association: A Case Report and Review of Literature

Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, also known as Mullerian aplasia/Mullerian agenesis, is characterized by the absence of the uterus and upper two-thirds of the vagina in women who have normal ovarian function and secondary sexual characteristics. The syndrome occurs at a rate of approximately 1 in every 4500–5000 females. Its primary clinical presentation is primary amenorrhea. MRKH syndrome varies in severity and is classified into two types: type I, which is isolated, and type II, involving abnormalities in other organ systems, particularly the kidneys and skeleton. Due to the nature of this condition, individuals with MRKH syndrome may experience significant psychological challenges, highlighting the importance of counseling. This case report describes the diagnosis of type II MRKH syndrome in a 14-year-old girl with primary amenorrhea, also associated with Mullerian duct aplasia–renal dysplasia–cervical somite anomalies.

Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization.

The upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single-cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region-specific epithelial and mesenchymal subpopulations and then deduced region-specific ligand-receptor pairs mediating mesenchymal-epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ-specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper MD development, and provides a manageable list of potential genes, pathways, and region-specific cell subtypes for future functional studies.

Robot-Assisted Radical Prostatectomy on a Patient with Large Mullerian Duct Cyst

Robot-Assisted Radical Prostatectomy on a Patient with Large Mullerian Duct Cyst

A RARE CASE OF OVARIAN AGENESIS AND HYPOPLASTIC UTERUS IN A PREPUBERTALGIRL WITH NORMAL 46, XX KARYOTYPE

Delayed onset of puberty and primary amenorrhea pose diagnostic challenges, often associated with diverse etiologies including hypothalamic-pituitary disorders, gonadal dysgenesis, and müllerian duct malformations.Historically, such syndromes have been associated with XY chromosomal components, but rare cases in karyotypically normal females (46, XX) have been reported. Comparisons with similar cases, including atypical forms of Mayer-Rokitansky-Küster-Hauser (MRKH) syndromeare made, highlighting the rarity of this condition. Despite advancements, the genetic basis remains unspecified, underscoring the need for further research. We present a unique case of gonadal agenesis and hypoplastic uterus in a 46,XX individual, without associated organ system anomalies, contributing to primary amenorrhea. Diagnostic evaluations including hormonal assessment, and pelvic MRI confirmed the absence of ovaries and severe hypoplasia of paramesonephric duct (PMND) derivatives. Treatment with 17beta estradiol successfully induced puberty, highlighting the clinical importance of timely intervention. Early detection of such cases is crucial for providing comprehensive support and improving patient outcomes.

Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric Müllerian duct development by eliminating asymmetric gene expression in Japanese quail embryos.

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3β-HSD) and estrogen receptor-β, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.

A rare variant of mullerian agenesis: a case report and review of the literature

IntroductionMenstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here.Case reportWe present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri—a horseshoe band cervix—were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation.ConclusionMullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.

Cryptomenorrhea due to Agenesis of Upper Part of Vagina Treated by Vaginoplasty with Amnion Graft and Cervicovaginal Anastomosis: a Case Report

Cryptomenorrhea due to vaginal agenesis is a rare developmental anomaly of Mullerian duct. It may be complicated by retrograde menstruation, endometriosis and acute or chronic pelvic infection. We report a case of a 12-year-old girl who presented with a history of severe cyclical lower abdominal pain for 2 months. Her clinical examination revealed well developed secondary sexual characteristics, slightly bulged lower abdomen with a palpable tender mass and a short blind vagina. Ultrasound imaging showed hematometra, hematocervix and vaginal agenesis. She was treated by vaginoplasty with amnion graft and cervicovaginal anastomosis with serial vaginal dilatation using plastic vaginal mold. The patient was symptom free with regular menstruation on follow up visit at 1, 3 and 9 months. The Uterus was normal in size with empty cavity and well-defined endometrial lining on ultrasound. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):49-51

Persistent Paramesonephric (Müllerian) Duct Remnant in Male Patients: Report of 2 Cases Presenting as Pelvic Masses.

Persistent Paramesonephric (Müllerian) Duct Remnant in Male Patients: Report of 2 Cases Presenting as Pelvic Masses.

Sub-Septate Uterus: An Incidental Radiological Finding in a Woman with History of Recurrent Miscarriage. A Case Report

Background: The septate uterus, which is the most common Mullerian duct anomaly, results from the abnormal fusion of the Mullerian duct during embryonic life, and it is usually associated with poor obstetric outcomes such as recurrent spontaneous abortions, subfertility, preterm labour, and reproductive failure. A large proportion of the patients that are affected remain asymptomatic owing to lack of indication for abdominal ultrasound before conception, and the problems are mainly detected after several pregnancy losses. The exact aetiology of the septate uterus is unknown but is caused by incomplete resorption of the uterovaginal septum after fusion of the Mullerian duct during embryogenesis. Case Presentation: We present a 32-year-old Para 0+3 woman referred to the radiology department for ultrasonography and hysterosalpingography (HSG) on account of recurrent miscarriage, which occurs within the first trimester of gestation. She has had three (3) consecutive miscarriages within the last 4 years, of pregnancies which were achieved spontaneously and were lost between the gestational ages of 9-12 weeks. She was investigated with ultrasonography, which demonstrated a bulky uterine appearance with two endometrial cavities that is connected to one cervical canal. Hysterosalpingography (HSG) showed a contrast-filled partly divided uterus with inter-cornual angles of 34º and intercornual distance of 1.92cm. The patient had hysteroscopic septum resection with a satisfactory outcome given addressing other medical problems that could militate against conception and has been on monthly follow-up. Conclusion: Radiological investigation of patients with recurrent miscarriages is indispensable for optimal evaluation to achieve accurate diagnosis and identify women whose problems are amenable to specialized treatments.

Pregnancy in the uterus rudimentary horn (literature review)

Pregnancy in the uterus rudimentary horn (PURH) is a rare form of ectopic pregnancy that develops in women suffering from abnormalities in the development of growth and fusion of the Mullerian paramesonephral ducts. A literature search was conducted in the Web of Science, eLIBRARY.ru, Scopus, PubMed/MEDLINE databases using key words “ectopic pregnancy”, “anomaly”, “complication”, “rudimentary uterine horn”, “diagnosis”, “management”. We selected articles published from 2014 to 2022. A methodological filter was not used to exclude the omission of suitable articles. The study included full-text papers and literary reviews on the subject under study, articles that are not directly related to the topic of PURH were excluded. In order to avoid the inclusion of duplicate publications in the literature review, if two papers by the same authors were found, the study period of each author was studied, and if the dates coincided, the most recent publication was selected. Usually, the PURH is overlooked and can lead to such a formidable complication as hemoperitoneum. Diagnosis and treatment of PURH remains a difficult task. Many women with rudimentary uterine horn have an acute rupture of the uterus during pregnancy. Early diagnosis is the key to successful treatment. Clinicians of various specialties should maintain a high degree of vigilance to prevent morbidity associated with this life-threatening condition.

MAP3K1 regulates female reproductive tract development.

Mitogen-activated protein 3 kinase 1 (MAP3K1) has a plethora of cell type-specific functions not yet fully understood. Herein, we describe a role for MAP3K1 in female reproductive tract (FRT) development. MAP3K1 kinase domain-deficient female mice exhibited an imperforate vagina, labor failure and infertility. These defects corresponded with shunted Müllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal-urogenital sinus fusion in neonates. The MAP3K1 kinase domain is required for optimal activation of the Jun-N-terminal kinase (JNK) and cell polarity in the MD epithelium, and for upregulation of WNT signaling in the mesenchyme surrounding the caudal MD. The MAP3K1-deficient epithelial cells and MD epithelium had reduced expression of WNT7B ligands. Correspondingly, conditioned media derived from MAP3K1-competent, but not -deficient, epithelial cells activated a TCF/Lef-luciferase reporter in fibroblasts. These observations indicate that MAP3K1 regulates MD caudal elongation and FRT development, in part through the induction of paracrine factors in the epithelium that trans-activate WNT signaling in the mesenchyme.

Abstract A007: Single nuclei analysis of uterine serous carcinoma reveals racial differences in immune signaling

Abstract Endometrial cancer (EC) is a growing public health concern, as incidence rates continue to rise every year. Even more troubling is the unequal survival rates between racial groups with EC, as Black EC patients are dying at twice the rate of white EC patients. Uterine serous carcinoma (USC) is an aggressive subtype of EC that affects Black patients more frequently than white patients. While USC accounts for only 10-15% of all reported EC cases, it has a disease specific mortality rate of over 40%. It is currently unclear what is causing the racial differences in subtype frequency and survival rate of USC. To gain insight on the transcriptomic differences of tumor cells and cells within the tumor microenvironment (TME), we performed single-nuclei RNA sequencing of 13 USC tumors, with 9 tumors from Black patients and 4 from white patients. We found significant gene expression differences, including the upregulation of PAX8 in tumors of Black patients. PAX8 is a lineage factor important in Mullerian duct tissues and is frequently upregulated in EC. In PAX8 high tumor cells, signaling pathways such as TGBF, JAK- STAT, and NFKB activity was enriched, while PAX8 low cells were enriched for p53, WNT, and estrogen signaling. To understand if PAX8 directly affects epithelial immune signaling, we performed RNA-seq on PAX8 knock down (KD) ARK2 cells. Analysis of DEGs showed that PAX8 KD cells express high IL-1A and IL-1B, while chemokines such as CXCL1 and Midkine were downregulated. When conditioned media (CM) from PAX8 KD cells were added to THP-1 macrophages, decreased levels of anti-inflammatory markers such as ARG1 and TGFB1 were observed, compared to PAX8 expressing cells. Additionally, pro-inflammatory molecules such as TNFa and IL-6 were expressed at higher levels. These observations were validated by a cytokine antibody array; macrophages treated with PAX8 KD CM secreted higher levels of pro- inflammatory cytokines such as IL-1A, IL-1B, IL-6, and CXCL5. Anti-inflammatory molecules such as TGFB1 and TGFB2, and growth factors such as FGF6 and FGF7, were secreted at lower levels than control. These studies indicate that PAX8 is a novel regulator of the epithelial- immune axis, which is upregulated in USC compared to normal tissue and modulates the TME in favor of immune suppression and tumor growth. Because PAX8 expression is higher in tumors of Black patients compared to white, this may indicate that Black patients have a higher degree of immunosuppression. Our studies are the first to report tumor differences between Black and white USC patients at the single nuclei level. Additionally, we report findings from the first study to use single nuclei sequencing to study a tumor from Black USC patients. Our results indicate that taking race into account when determining treatment for USC may improve outcomes for Black patients. Citation Format: Grace Foley, J. Julie Kim. Single nuclei analysis of uterine serous carcinoma reveals racial differences in immune signaling [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A007.

A rare case of persistent mullerian duct syndrome with adenocarcinoma of ascending colon

Persistent mullerian duct syndrome (PMDS) is a rare congenital disorder. This condition results from a failure of Mullerian duct regression during fetal development, leading to the presence of uterus, fallopian tubes, and upper vagina in otherwise phenotypically male individuals. Radiological evaluation plays a crucial role in the diagnosis and management of PMDS. Various imaging modalities including ultrasound, magnetic resonance imaging, and computed tomography are employed to visualize and confirm the presence of Mullerian structures in affected individuals.

Ohvira syndrome with rare presentations – A case report

Herlyn Werner Wunderlich syndrome is a very rare congenital anomaly of the urogenital tract involving Mullerian ducts and mesonephric ducts. It is synonymous with OHIVRA syndrome which is Obstructed Hemivagina with Ipsilateral Renal Agenesis syndrome. Very few case reports have been reported regarding the syndrome. Herein, we report a case of 20 year old unmarried female with unusual presentation of OHVIRA syndrome with complaints of spotting per vagina and with vaginal cyst on examination. Diagnosis was confirmed by MRI which showed features of OHVIRA with pyometra caused by the obstructed hemivagina. She was managed surgically by diagnostic laparoscopy and per vaginal resection of the vaginal septum and drainage of around 50cc of pyometra followed by visualisation of two separate cervical canals post procedure. As a rare entity, a high degree of clinical suspicion is necessary to diagnose and intervene at the right time to ensure optimum results and prevent complications and preserve fertility.

Frequency and types of congenital uterine anomalies during caesarean section: A prospective cohort study

: Congenital uterine anomalies are due to mal-development of the mullerian ducts. They can lead to adverse reproductive outcomes like recurrent miscarriage, preterm birth, foetal malpresentation and subfertility. Prevalence of congenital uterine anomalies is 5-7%. To find the frequency and types of congenital uterine anomalies during caesarean section. This is a prospective cohort study done at SDM College of Medical Sciences and Hospital, Dharwad, India from August 2020 to July 2021. 2932 women undergoing caesarean section participated in the study. The uterus was examined thoroughly. The type of uterine anomaly was noted. : There were 22 cases of congenital uterine anomalies (CUAs) during caesarean section. Prevalence of CUA was 0.75%. There was increased incidence of miscarriage(27%), pre-eclampsia (31.8%), foetal malpresentation (31.8%), foetal growth restriction (9%) and preterm caesarean section (40.9%) among women with a uterine anomaly. Commonest type of CUA was unicornuate uterus (31.8%), followed by septate (27.2%), arcuate (22.7%) and bicornuate uterus (18.1%). Poorest outcomes were seen with septate and unicornuate uteri.: Caesarean section provides an opportunity to diagnose congenital uterine anomalies. This information can be used to plan their future reproductive life. Exploring the uterus to look for uterine anomalies after delivery of the fetus and placenta has to be done and documented.

Segmental aplasia of the paramesonephric duct in a New Zealand white rabbit and a review of the literature.

In females, the paramesonephric (syn: Müllerian) duct gives rise to the uterine tubes, uterus, cervix, and part of the vagina. Segmental uterine aplasia resulting from a paramesonephric duct abnormality has been reported in a range of species including bovids, canids, felids, equids, camelids, and lagomorphs. Here we document segmental aplasia of the left paramesonephric duct in a New Zealand white rabbit. The proximal 70 mm of the left uterine tube was present and terminated in adipose tissue. A 10 × 2 × 1-mm tag of cream tissue was present and was composed of sheets of adipose tissue and streams of smooth muscle, but otherwise, there was no evidence of the left uterine horn, supporting a diagnosis of unilateral uterine aplasia (uterus unicornis) analogous to a human class II (unicornuate uterus) lesion of the "no horn" subtype. In addition, our case had a concurrent uterine tube fimbrial cyst, minor cysts in the left kidney, and mammary gland hyperplasia with secretory activity. We suggest the adoption of a uniform classification system specifically for lagomorph uterine anomalies. Large-scale multi-center studies documenting prevalence of such lesions would facilitate identification of trends in laterality and other factors.

Establishment of an organ culture system to maintain the structure of mouse Müllerian ducts during development.

We previously showed that the anti-Müllerian hormone (AMH), infiltrating from the testis to the mesonephros reaches the cranial and middle regions of the Müllerian duct (MD) and induces their regression using an organ culture in mice. However, it is difficult to maintain structural integrity, such as the length and diameter and normal direction of elongation of the caudal region of the MD, in conventional organ culture systems. Therefore, the pathway of AMH to the caudal MD region remains uncharted. In this study, we established an organ culture method that can maintain the morphology of the caudal region of the MD. The gonad-mesonephros complex, metanephros, and urinary bladder of mouse fetuses at 12.5 dpc attached to the body trunk were cultured on agarose gels for 72 hr. The cultured caudal region of the mesonephros was elongated along the body trunk, and the course of the mesonephros was maintained in many individuals. In males, mesenchymal cells aggregated around the MD after culture. Moreover, the male MD diameter was significantly smaller than the female. Based on these results, it was concluded that the development of the MD was maintained in the present organ culture system. Using this culture system, AMH infiltration to the caudal region of the MD can be examined without the influence of AMH in the blood. This culture system is useful for clarifying the regression mechanism of the caudal region of the MD.

Navigating a Rare Presentation: Case Report of a Large Gartner’s Duct Cyst

Background: Mullerian ducts form the female genital tract and wolffian ducts form the male genital tract. In females, sometimes the wolffian duct persists and form the Gartner duct and its total or partial occlusion results in the formation of Gartner’s cyst. It is typically small and asymptomatic and occurs along the antero-lateral wall of vagina. Methods and Results: We report a case of 40-year-old woman who presented with a big mass coming out per vaginum. After examination, she was provisionally diagnosed as Gartner duct cyst, excision was done and confirmed as a case of Gartner’s duct cyst on histopathological examination. Conclusion: A good clinical examination along with radiological investigations aids in making a timely diagnosis and surgical management.

Bicornis unicollis uterus as a risk factor of preterm birth: A case of young woman with multiple premature births.

Bicornis unicollis uterus is a rare congenital uterine abnormality that occurs due to the failure of Mullerian duct fusion early in the development of the female internal genitalia system. In this case report, we present a woman with bicornis unicollis uterus who had preterm birth. A 30-year-old female patient with two caesarean sections history with premature babies was presented to the hospital with a complaint of regular contractions for twelve hours in her third preterm pregnancy. The patient has no particular symptoms besides acute abdominal pain. The ultrasonography examination indicated a uterus didelphys with breech presentation fetus. Due to the patient's caesarean history and the fetal presentation, an emergency caesarean section was decided and performed. It was found that the gravid uterus was on the left and the baby was subsequently delivered with a complete placenta. Postoperative condition of the patient was shown to be stable while the baby underwent an intensive care at the neonatal intensive care unit. This case report highlights that early diagnosis in this rare case is critical since bicornis unicollis uterus are mostly asymptomatic. Caesarean section was chosen in the present case based on consideration of the fetal and maternal clinical conditions.

Co-existence of Morgagni’s cyst with a twisted vas aberrans and “bell clapper” deformity in a 15-year-old boy: a case report

BackgroundThe testicular appendix is a residual of the paramesonephric and mesonephric duct, most commonly found close to the superior pole of the epididymis as Morgagni’s cyst. Torsion of such cysts is a common event in children, and the patient usually presents with a palpable testis with a tender mass in its upper pole. The co-existence of two or more appendices is very rare. In addition to the fact that Morgagni’s cyst was the non-twisted one and vas aberrans was, made clinical and radiological diagnosis difficult.Case presentationOur patient, a 15-year-old boy, presented with persistent pain in the right scrotum, a significant palpable mass accompanied by vomiting. Upon surgical exploration, a large dark cyst was found located on the right side of the right testicle with a 720-degree torsion. The cyst was straightened and excised along with a Morgagni’s cyst. The testis was fixed in the right hemiscrotum due to a “bell clapper” deformity that was also a finding.ConclusionsPathological findings were consistent with a twisted cyst of a testicular appendix (vas aberrans). Co-existence of two or more appendices is very rare in addition to the fact that Morgagni’s cyst was the non-twisted one. Usually and in very few cases, a second appendix is found randomly, during surgical exploration for acute scrotum due to torsion of Morgagni’s cyst.