Fig 12 - uploaded by Gerald R. Cunha
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Sagittal sections of a 16-week human female fetal reproductive tract immunostained with PAX2 (A-B) and FOXA1 (C-D). FOXA1-reactive epithelial cells form all of the solid vaginal plate (C-D). PAX2-reactive epithelial cells constitute a epithelium lining the lumen of the uterovaginal canal (A-B). Scale bar in A also refers to D. Scale bar in D also refers to C. From Robboy et al. (2017) with permission.
Source publication
Development of the human female reproductive tract is reviewed from the ambisexual stage to advanced development of the uterine tube, uterine corpus, uterine cervix and vagina at 22 weeks. Historically this topic has been under-represented in the literature, and for the most part is based upon hematoxylin and eosin stained sections. Recent immunohi...
Citations
... The protein-coding sequence is in the region from 278 to 1696 bp in the mRNA, with a size of 1419 nucleotides. FOXA1 is a protein-coding gene, and its encoded protein consists of 472 amino acids, with a molecular weight of 49,148 Da [25][26][27]. The functional structure of FOXA1 includes the N-terminal transactivation domain, centrally shared DNA-binding domain common to the family, and C-terminal transactivation domain associated with histone H3/H4 [14]. ...
... The fallopian tubes are a crucial component of the female reproductive tract originating from the M€ ullerian ducts, which serve as a conduit connecting the ovary to the uterus and play an indispensable role in facilitating fertilization and supporting preimplantation embryonic development. 1 Problems, such as hydrosalpinx, inflammation, or anomalies of the fallopian tubes, can cause infertility and ectopic pregnancy. The congenital ampulla and fimbria discontinuity of the fallopian tube is rare and may be incidentally found during laparoscopy. ...
We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.
... The sociodemographic data included race/ethnicity, age, and BMI. The age was divided into three subgroups based on the development of the female reproductive system, namely 14-20 years, 20-35 years, and ≥35 years [20]. BMI was divided into four subgroups according to international reference standards: <18.5 kg/m 2 , 18.5-24.9 ...
Objective
Preventing adverse events due to unstable oxygen saturation (SpO2) at night in pregnant women is of utmost importance. Poor sleep has been demonstrated to impact SpO2 levels. Nowadays, many gravida have a habit of prolonged exposure to light before sleep, which can disrupt their sleep. Therefore, this study aimed at investigate the relationship between lights-out time, sleep parameters and SpO2, exploring the underlying mechanisms.
Methods
The data of 2881 eligible subjects from the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be and Sleep Disordered Breathing (nuMOM2b-SDB) database were analyzed. Multiple linear regression models were used to investigate the relationship between lights-out time and SpO2. In addition, restricted cubic splines (RCS) were employed to fit the nonlinear correlation between the two variables. The smoothing curve method was further utilized to depict the relationship between lights-out time and SpO2 based on various subgroup variables.
Results
All participants were categorized according to race/ethnicity. A negative correlation was observed between nighttime lights-out time and average value of SpO2 (Avg-SpO2) (β = −0.05, p = 0.010). RCS revealed a U-shaped relationship between lights-out time and Avg-SpO2, with the turning point at 22:00. The subcomponent stratification results indicated that the Avg-SpO2 and minimum value of SpO2(Min-SpO2) of advanced maternal age decreased as the lights-out time was delayed. Furthermore, overweight and obese gravida showed lower Avg-SpO2 and Min-SpO2 levels than normal weight.
Conclusions
A U-shaped relationship was identified between lights-out time and nocturnal Avg-SpO2 during early pregnancy, with the inflection at 22:00. Notably, later lights-out times are associated with lower levels of Min-SpO2 for advanced maternal age. The findings suggest that appropriately adjusting the duration of light exposure before sleep and maintaining a relatively restful state may be more beneficial for the stability of SpO2 in pregnant women. Conversely, deviations from these practices could potentially lead to pathological alterations in SpO2 levels.
... The female reproductive tract develops from the mullerian ducts, which form on both sides and are completed around the 12th to 14th week of pregnancy (7). When fusion is complete, canalization and absorption of the medial part leads to the formation of a normal uterine cavity and vagina. ...
Objective: In this study, we aimed to determine the incidence of incidental uterine anomalies in the patient population who gave birth in our centre and to evaluate the perinatal outcomes. Methods: We conducted a retrospective analysis of outcomes of patients with incidental uterine anomalies who delivered at a tertiary care center between January 2023 and December 2023. Patient data were obtained by searching hospital records. Results: The data of 782 pregnant women who had given birth in the last eleven months were analyzed retrospectively. Three patients were found who could be included in the classification of uterine anomaly and who had not received prior diagnosis and treatment. The mean age was 30.0 years and the mean body mass index was 25.6 kg/m2. The mean gestational age of the patients was 37+0 weeks. Conclusion: In this study, we found uterine abnormalities in 3 patients during cesarean delivery. It is important to note that these uterine abnormalities correlate least with pregnancy complications or fertilization success.
... The pathogenesis of MRKH syndrome is complex and likely involves multiple factors contributing to tissue patterning and organ morphogenesis during human embryonic development [5]. This may include genetic factors, soluble morphogens, chemical cues, and mechanical forces, among others [6]. ...
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition that affects a small proportion of female individuals at birth, resulting in the absence or underdevelopment of reproductive organs. However, this case report introduces overactive bladder (OAB) and vulvodynia, conditions that have not been previously reported in MRKH patients. The 36-year-old patient began developing breast tissue around the age of 12 but never experienced menstruation. Simultaneously, she started experiencing discomfort in the genital region and frequent urination. These symptoms gradually worsened, making it difficult for her to continue her education, and initially, she was misdiagnosed with a developmental disorder. Typically, the general understanding of MRKH syndrome has focused on reproductive anomalies, but this case underscores its diversity. Diagnostic assessments, including ultrasound, MRI, and various tests, revealed that the patient's severe genital discomfort and urinary symptoms were improved through a specialized Neodymium YAG laser therapy named "PIANO mode," resulting in significant symptom relief and improved quality of life. This report emphasizes the importance of comprehensive and individualized approaches to managing MRKH syndrome. It aims to raise awareness that MRKH syndrome, while often associated with reproductive abnormalities, can also involve related symptoms like OAB and vulvodynia, which can significantly impact daily life.
... Another interesting hypothesis is that the GPs are homologous to the junction of MDs with the urogenital sinus in mammals. Failure to establish a connection between the MDs and urogenital sinus can lead to various developmental anomalies in the female genital tracts, including vaginal agenesis, as observed in mice (Zhao et al., 2016) and humans (Cunha et al., 2018;Parodi et al., 2022). Although the molecular mechanisms governing this connection are currently unknown, it has been suggested that retinoic acids play a role in this process (Nakajima et al., 2019). ...
Mature gametes are transported externally for fertilization. In vertebrates, the gonads are located within the coelom. Consequently, each species has specific organs for export, which often vary according to sex. In most vertebrates, sperm ducts and oviducts develop from the Wolffian and Müllerian ducts, respectively. However, exceptions exist. Both sexes of cyclostomes, as well as females of basal teleosts, lack genital ducts but possess genital pores. In teleosts of both sexes, genital ducts are formed through the posterior extensions of gonads. These structures appear to be independent of both Wolffian and Müllerian ducts. Furthermore, the development of Wolffian and Müllerian ducts differs significantly among various vertebrates. Are these gamete-exporting organs homologous or not? A question extensively debated around the turn of the 20th century but now largely overlooked. Recent research has revealed the indispensable role of Wnt4a in genital duct development in both sexes of teleosts: zebrafish and medaka. wnt4a is an ortholog of mammalian Wnt4, which has functions in Müllerian duct formation. These results suggest a potential homology between the mammalian Müllerian ducts and genital ducts in teleosts. To investigate the homology of gamete-exporting organs in vertebrates, more detailed descriptions of their development across vertebrates, using modern cellular and genetic tools, are needed. Therefore, this review summarizes existing knowledge and unresolved questions on the structure and development of gamete-exporting organs in diverse vertebrate groups. This also underscores the need for comprehensive studies, particularly on cyclostomes, cartilaginous fishes, basal ray-finned fishes, and teleosts.
... During the seventh to eighth week of embryogenesis, the Mullerian ducts lie between the Wolfian ducts and adjacent to the urogenital septum. During this period, specific teratogen agents are believed to cause embryological arrest affecting both the Mullerian and Wolfian ducts, resulting in HWW syndrome [10] . Different studies suggest that this embryological arrest may be caused by several different genetic, Fig. 4 -CT urography (A) CT urography showing absent right kidney (B) excretory phase showing hypertrophic left kidney. ...
Herlyn-Werner-Wunderlich (HWW) syndrome is a rare and complex congenital anomaly of the genitourinary system characterized by uterus didelphys, an obstructed hemivagina, and ipsilateral renal agenesis. It is the result of the maldevelopment of both the Mullerian and Wolffian ducts. Clinical manifestations of dysmenorrhea, dysuria, and urinary retention appear after menarche due to the accumulation of menstrual blood and distention of the obstructed hemivagina. Diagnosis of this anomaly is often delayed, and the obstructive nature of the condition is missed due to cyclic menstruation from the one canalized hemivagina. This case report represents a typical form of HWW syndrome to highlight the importance of considering this rare entity in an adolescent girl presenting with signs of dysmenorrhea and urinary complaints. A 13-year-old patient was presented at the obstetrics and gynecology clinic due to low abdominal pain and urinary retention on the fifth day of menstruation. For the last 6 months, the patient suffered progressive cyclic low abdominal pain associated with menstruation. Inspection of the external genitalia was unremarkable, and the hymenal membrane had a normal oval opening. An ultrasound examination revealed the sonographic features of the didelphys uterus and was suggestive of a right obstructed hemivagina with hematocolpos. Magnetic resonance imaging and computed tomography urography showed evidence of didelphys uterus, right blind obstructed hemivagina associated with huge hematocolpos, and ipsilateral renal agenesis. The diagnosis of HWW syndrome was established. Surgical resection of the vaginal septum was undertaken without delay, and the patient was discharged the following days.
... In contrast, when an embryo lacks the Y chromosome, and thus the sex-determining region Y, there is no formation of the testes. Therefore, anti-Müllerian hormone and testosterone are not produced and this eventually leads toward development of female sex organs (Healey, 2012;Cunha et al., 2018). Effects on reproductive system development were studied for two types of MNP, polystyrene and polyethylene. ...
Plastic production has greatly increased in the past decades and has become central to modern human life. Realization is dawning that plastics break down into smaller pieces resulting in micro- or nanoplastics (MNP) that can enter humans directly via the environment. Indeed, MNP have been detected in every part of the human body, including the placenta, which is concerning for development. Early developmental stages are crucial for proper growth and genome programming. Environmental disruptors in MNP can have detrimental effects during this critical window as well and can increase the risk of developing disease and dysfunction. In addition, MNP may impact situations in which developmental pathways are reactivated after birth such as during organ repair. Currently, there is no overview of how MNP can impair (human) development and repair. Therefore, we provide an extensive overview of available evidence on MNP impacting developmental and regenerative processes in various organs in humans and rodent models. In addition, we have included the impact of some additives that can leach from these MNP. We conclude that MNP and their additives can have modulating effects on developing and regenerating organs.
... We engineered a human vagina chip by co-culturing primary human vaginal epithelium on the top surface of an extracellular matrix-coated porous membrane within the top channel of a two-channel microfluidic chip with primary human uterine fibroblasts on the lower surface of the same membrane in the bottom parallel channel to recreate the vaginal epithelial-stromal interface in vitro (Fig. 1A), which has been shown to be important for development of the vaginal epithelium [36,37]. The top and bottom channels of the vagina chip were respectively perfused with epithelial and stromal growth medium for 5 days to expand cell populations before replacing the epithelium medium with HBSS (LB/+G) [pH ~ 4.7] and the stromal medium with a differentiation medium that supports optimal viability and epithelial stratification (see "Methods" section). ...
The vaginal microbiome plays an important role in vaginal health and disease. For example, certain Lactobacillus species dominate in a healthy vagina, while disruption of the microbial status quo is associated with disease. Therapies to manipulate the vaginal microbiome are therefore promising for preserving vaginal health, but no preclinical models have been able to faithfully replicate the vaginal epithelial microenvironment for experimentation, until now. Researchers at the Wyss Institute at Harvard have just developed the Vagina Chip, a 3D in vitro model featuring a functional vaginal epithelium. When assemblages of beneficial vaginal microbes like Lactobacillus crispatus are grown on the chips, the epithelial cells remain healthy. In addition, beneficial D- and L-lactate accumulate, a normal vaginal pH is maintained, and proinflammatory molecules are downregulated. In contrast, when groups of harmful bacteria like Gardnerella vaginalis are grown on the chips, the epithelial cells become damaged and the pH and proinflammatory cytokine levels increase, consistent with the pathological changes in a human vagina with an unhealthy microbiome. Although additional confirmation is needed, the findings demonstrate that the new Vagina Chip is a promising preclinical model that can be used to clarify vaginal epithelium– microbiome interactions and test new therapies.
... 5 In females, the absence of fetal testicular hormones (mainly testosterone and androstenedione) and anti-mullerian hormone (a product of Sertoli cells in males) determines a default process by which the MD regress, 5 and female phenotypic development of the mullerian duct ensues. 6 Several genes are involved in this process, including paired box genes (PAX2 and PAX8), homeobox genes (EMX2, LIM1, HOXA9, HOXA10, HOXA11 and HOXA13), anti-mullerian hormone, epidermal growth factor receptor and AR, which act in a complex interplay requiring mesenchymal/epithelial signalling. Interestingly, AR is expressed in humans only in the epithelium of the MD. ...
Mesonephric remnants (MRs) are embryonic vestiges most commonly found in female pathology specimens from the lateral wall of the cervix. The highly regulated genetic programme of mesonephric duct development has been well characterised in animals based on traditional surgical castration and knockout mouse experiments. However, the process is incompletely understood in humans. MRs are believed to give rise to mesonephric neoplasms, which are rare tumours with uncertain pathophysiology. There is a dearth of molecular studies on mesonephric neoplasms in part due to their rarity. Here, we report the results of next-generation sequencing of MR, which identified amplification of the androgen receptor gene for the first time to the best of our knowledge and discuss the potential implications in the context of the literature.
