Uterotubal Junction Research Articles

Exploring swine oviduct anatomy through micro-computed tomography: a 3D modeling perspective.

The oviduct plays a crucial role in the reproductive process, serving as the stage for fertilization and the early stages of embryonic development. When the environment of this organ has been mimicked, it has been shown to enhance in vitro embryo epigenetic reprogramming and to improve the yield of the system. This study explores the anatomical intricacies of two oviduct regions, the uterotubal junction (UTJ) and the ampullary-isthmic junction (AIJ) by using micro-computed tomography (MicroCT). In this study, we have characterized and 3D-reconstructed the oviduct structure, by measuring height and width of the oviduct's folds, along with the assessments of fractal dimension, lacunarity and shape factor. Results indicate distinct structural features in UTJ and AIJ, with UTJ displaying small, uniformly distributed folds and high lacunarity, while AIJ shows larger folds with lower lacunarity. Fractal dimension analysis reveals values for UTJ within 1.189-1.1779, while AIJ values range from 1.559-1.770, indicating differences in structural complexity between these regions. Additionally, blind sacs or crypts are observed, akin to those found in various species, suggesting potential roles in sperm sequestration or reservoir formation. These morphological differences align with functional variations and are essential for developing an accurate 3D model. In conclusion, this research provides information about the oviduct anatomy, leveraging MicroCT technology for detailed 3D reconstructions, which can significantly contribute to the understanding of geometric-morphological characteristics influencing functional traits, providing a foundation for a biomimetic oviduct-on-a-chip.

Uterotubal junction of the bovine (Bos taurus) versus the dromedary camel (Camelus dromedarius): Histology and histomorphometry.

This study aims to conduct a comparative analysis of the uterotubal junction in two distinct mammalian species, the bovine (Bos taurus) and the dromedary camel (Camelus dromedarius), focusing on histological and histomorphometric parameters. Uterotubal junction (UTJ) was dissected from 8 cows and 12 camels with dominant follicles, and processed for H&E staining for histology, and histomorphometry examination. The results showed that the camel uterotubal junction papillae (UTJP) existed only in camels and was completely absent in cattle. Histologically, the cow UTJ appears with a star-shaped lumen, and the mucosa is lined by a simple columnar epithelium with ciliated and non-ciliated cells. Superficial (SG) and deep glands (DG) were abundant in the submucosa. Camel UTJP is a conical structure, it has a pale yellowish colour, 0.5 ± 0.2 cm height, and 0.3 ± 0.1 cm width, and it has a distinct sphincter at the tip towards the uterine lumen. In the camel UTJP, the lumen is wider, and the mucosa showed large multiple folds lined with ciliated and non-ciliated cells in a pseudostratified columnar epithelium. The submucosa showed no mucosal glands. Lumen area, lumen epithelial height, luminal epithelial density, the thickness of the muscular layer, number of folds, fold height, epithelial height, fold area and epithelial perimeter were higher in camel UTJP (p < .001) than cow UTJ, while the total endosalpinx area and glandular epithelial density were lower in camel UTJP (p < .001) than in cow UTJ. In conclusion, this study elucidates potential variations in the uterotubal junction between bovines and dromedary camels, providing valuable insights into their reproductive adaptations. The epithelial lining, absence of glands and the thick layer of tunica muscularis might indicate that camel UTJP could play a mechanical role in selecting spermatozoa and assisting the hatching of blastocysts during their passage into the uterus.

Generation of Oviductal Glycoprotein 1 Cre Mouse Model for the Study of Secretory Epithelial Cells of the Oviduct.

The epithelial cell lining of the oviduct plays an important role in oocyte pickup, sperm migration, preimplantation embryo development, and embryo transport. The oviduct epithelial cell layer comprises ciliated and nonciliated secretory cells. The ciliary function has been shown to support gamete and embryo movement in the oviduct, yet secretory cell function has not been well characterized. Therefore, our goal was to generate a secretory cell-specific Cre recombinase mouse model to study the role of the oviductal secretory cells. A knock-in mouse model, Ovgp1Cre:eGFP, was created by expressing Cre from the endogenous Ovgp1 (oviductal glycoprotein 1) locus, with enhanced green fluorescent protein (eGFP) as a reporter. EGFP signals were strongly detected in the secretory epithelial cells of the oviducts at estrus in adult Ovgp1Cre:eGFP mice. Signals were also detected in the ovarian stroma, uterine stroma, vaginal epithelial cells, epididymal epithelial cells, and elongated spermatids. To validate recombinase activity, progesterone receptor (PGR) expression was ablated using the Ovgp1Cre:eGFP; Pgrf/f mouse model. Surprisingly, the deletion was restricted to the epithelial cells of the uterotubal junction (UTJ) region of Ovgp1Cre:eGFP; Pgrf/f oviducts. Deletion of Pgr in the epithelial cells of the UTJ region had no effect on female fecundity. In summary, we found that eGFP signals were likely specific to secretory epithelial cells in all regions of the oviduct. However, due to a potential target-specific Cre activity, validation of appropriate recombination and expression of the gene(s) of interest is absolutely required to confirm efficient deletion when generating conditional knockout mice using the Ovgp1Cre:eGFP line.

Diagnostic and management dilemmas of pregnancies at the utero-tubal junction: A case series and management algorithm.

A pregnancy at the utero-tubal junction is a rare type of ectopic pregnancy and is associated with high maternal morbidity if it remains undetected. In the present study we discuss four cases of ectopic pregnancies at the utero-tubal junction which caused diagnostic and management dilemmas. Four cases of early pregnancies with the gestational sac (G-sac) implanted near the utero-tubal junction are described. In case 1 this was suspected after a failed attempt at dilatation and curettage at our hospital, cases 2 and 3 presented with amenorrhea and pain abdomen and case 4 was diagnosed on first pregnancy documentation scan after frozen embryo transfer. As initial two-dimensional (2D) transvaginal scan (TVS) failed to diagnose the exact location of the G-sac, three-dimensional (3D) TVS helped to localize the exact location of pregnancy and subsequent individualized management. Case 1 had a partial intramural ectopic pregnancy managed by laparotomy and removal of the ectopic sac. The second and third cases were eccentric uterine pregnancies. The fourth was an interstitial ectopic pregnancy managed by a laparoscopic loop and stitch technique. This case series describes the role of 3D TVS for the evaluation of pregnancies implanted at the utero-tubal junction and individual management of eccentric intrauterine, interstitial ectopic and intramural ectopic pregnancies. A diagnostic algorithm for such types of cases and management options is discussed.

Pregnancies at the Uterotubal Junction: A Review of Terminology (Interstitial, Cornual, and Angular) and Recommendations for Management.

Ectopic pregnancies are one of the most common causes of obstetric mortality worldwide. Interstitial ectopic pregnancies, defined as an extracavitary pregnancy within the portion of the Fallopian tube that transverses the myometrium, have reported mortality rates approximately seven times higher than all types of ectopic pregnancy combined. In contrast, intracavitary eccentric gestations, often labeled as "cornual" or "angular" pregnancies, have reportedly high rates of live birth. Unfortunately, the terms "interstitial," "cornual," and "angular" have long been used with varying diagnostic criteria and often interchangeably to describe a pregnancy near the uterotubal junction. The inconsistency in nomenclature and lack of clear diagnostic criteria to distinguish among these pregnancies has resulted in a paucity of data to provide accurate prognostic information and guide appropriate management. This review article aims to provide historical context for the terms "interstitial," "cornual," and "angular;" discuss previous and more recent innovations of diagnostic methods; and provide recommendations for concise terminology and inform management.

MicroRNA expression in specific segments of the pig periovulatory internal genital tract is differentially regulated by semen or by seminal plasma

microRNAs play pivotal roles during mammalian reproduction, including the cross-talk between gametes, embryos and the maternal genital tract. Mating induces changes in the expression of mRNA transcripts in the female, but whether miRNAs are involved remains to be elucidated. In the current study, we mapped 181 miRNAs in the porcine peri-ovulatory female reproductive tract: Cervix (Cvx), distal and proximal uterus (Dist-Ut, Prox-Ut), Utero-tubal-junction (UTJ), isthmus (Isth), ampulla (Amp), and infundibulum (Inf) when exposed to semen (natural mating (NM) or artificial insemination (AI-P1)) or to infusions of sperm-free seminal plasma (SP): the first 10 mL of the sperm rich fraction (SP-P1) or the entire ejaculate (SP-E). Among the most interesting findings, NM decreased mir-671, implicated in uterine development and pregnancy loss prior to embryo implantation, in Cvx, Dist-UT, Prox-UT, Isth, and Inf, while it increased in Amp. NM and SP-E induced the downregulation of miR-let7A-1 (Dist-UT, Prox-UT), a regulator of immunity during pregnancy. miR-34C-1, a regulator of endometrial receptivity gene expression, was increased in Dist-UT, UTJ and Amp (NM), in Prox-UT (AI-P1), and in Amp (SP-P1). miR-296, a modulator of the inflammatory response and apoptosis, was upregulated in the UTJ (all treatments). NM elicited the highest miRNA activity in the sperm reservoir (UTJ), suggesting that key-regulators such as miR-34c or miR-296 may modulate the metabolic processes linked to the adequate preparation for gamete encounter in the oviduct. Our results suggest that SP should be maintained in AI to warrant miRNA regulation within the female genital tract for reproductive success.

Classical Estrogen Signaling in Ciliated Epithelial Cells of the Oviduct Is Nonessential for Fertility in Female Mice.

Ciliary action performs a critical role in the oviduct (Fallopian tube) during pregnancy establishment through sperm and egg transport. The disruption of normal ciliary function in the oviduct affects oocyte pick-up and is a contributing factor to female infertility. Estrogen is an important regulator of ciliary action in the oviduct and promotes ciliogenesis in several species. Global loss of estrogen receptor α (ESR1) leads to infertility. We have previously shown that ESR1 in the oviductal epithelial cell layer is required for female fertility. Here, we assessed the role of estrogen on transcriptional regulation of ciliated epithelial cells of the oviduct using single-cell RNA-sequencing analysis. We observed minor variations in ciliated cell genes in the proximal region (isthmus and uterotubal junction) of the oviduct. However, 17β-estradiol treatment had little impact on the gene expression profile of ciliated epithelial cells. We also conditionally ablated Esr1 from ciliated epithelial cells of the oviduct (called ciliated Esr1d/d mice). Our studies showed that ciliated Esr1d/d females had fertility rates comparable to control females, did not display any disruptions in preimplantation embryo development or embryo transport to the uterus, and had comparable cilia formation to control females. However, we observed some incomplete deletion of Esr1 in the ciliated epithelial cells, especially in the ampulla region. Nevertheless, our data suggest that ESR1 expression in ciliated cells of the oviduct is dispensable for ciliogenesis and nonessential for female fertility in mice.

Counting Murine Corpora Lutea to Determine the Number of Oocytes Ovulated.

One can determine if and how many oocytes have been ovulated in a female mouse by counting the number of corpora lutea (CL) on the ovaries during the process of preimplantation embryo collection. A simple method of harvesting the ovaries and observing with a dissecting microscope and top lighting is provided along with a description of how to recognize CL. As the embryos rarely, if ever, cross the uterotubal junction, this provides a measure of the maximum number of embryos expected to be recovered from each oviduct or uterine horn, a number that can be valuable in analyzing early lethal mutations.

Hysteroscopic management of subfertility in cases with suspected endometrial polyps

Endometrial polyps (EPs) are a common benign gynecologic condition associated with abnormal uterine bleeding (AUB), infertility and recurrent pregnancy loss. Transvaginal ultrasound (TVU) provides an excellent diagnostic technique to identify the size and the anatomic location of endometrial polyps. Its accuracy increases when color Doppler, 3D investigation and saline-infused sonohysterography are used. However, hysteroscopy showed the highest diagnostic accuracy in infertile patients with suspected endometrial polyps and provides a safe and feasible opportunity for EPs removal. Objectives. This study aims to demonstrate the effectiveness of hysteroscopic polyps’ removal in infertile young female patients. Methodology. This study, conducted over a period of one year, included women who addressed our clinic for infertility. These patients were clinically examined and evaluated using transvaginal ultrasound (TVUS). Hysteroscopy was performed on all cases where TVUS raised the suspicion of endometrial polyps. Additionally, the incidence of pregnancies obtained within the first 12 months after the hysteroscopic removal of endometrial polyps was recorded. Results. Out of the cohort of 97 infertile patients, endometrial polyps were suspected in 33 patients. Before hysteroscopy, seven patients additionally underwent a sonohysterography (SHG) procedure. Abnormal uterine bleeding was the primary clinical manifestation (21 cases; 63.63%). EPs were histologically confirmed in 31 cases, and leiomyoma, in two cases. Of the 31 EPs cases, in 20 cases (64.51%) the localization was at the utero-tubal junction. Out of the 30 patients diagnosed with EPs and where the follow-up was possible, 18 individuals, constituting 60% of the group, successfully attained intrauterine pregnancies within the initial 12 months following their hysteroscopic procedure. Conclusions. Our study revealed a significant improvement in reproductive outcomes within the first year following EP resection. The prevalence of endometrial polyps has increased due to improved ultrasound techniques. SHG can potentially increase the ultrasound detection of endometrial polyps, especially in cases where the imagistic information is unclear. Nonetheless, hysteroscopy, known for its high diagnostic accuracy, remains the gold standard. Our research supports the importance of hysteroscopy for uterine cavity assessment and lesion management, and it highlights the increased chances of pregnancy after the lesion’s removal.

P-042 Sperm Selection Based on Speed Using Rheotaxis in a Parallel Array of Microfluidic Apertures

Abstract Study question Does selecting human spermatozoa using a dynamic microfluidic system impact semen parameters and genomic characteristics? Summary answer Flow rate adjustment in a dynamic microfluidic device selects spermatozoa with superior DNA integrity. It also appears to select a higher proportion of Y-chromosome-bearing spermatozoa. What is known already Mammalian spermatozoa demonstrate rheotactic motion against the flow. This is important in order to overcome the fluid drag force in the female genital tract to reach the oocyte. Sperm processing methods have been developed based on these principles; more recently, static and dynamic microfluidic devices have been tested due to the association between high progressive motility and greater genomic integrity. These devices also appear to have an impact on sperm sex selection. Study design, size, duration Human ejaculates (n = 7) were evaluated and simultaneously processed by density gradient centrifugation (DGC) or a novel microfluidic sperm sorter (MFSS) with an adjustable flow rate inspired by the constriction of the uterotubal junction. Concentration, motility, morphology, and SCF were assessed and compared between raw, DGC-, and MFSS-processed specimens. To identify differences in the SCF and the proportion of X- and Y-spermatozoa, spermatozoa isolated at different flow rates (150, 250, 350, and 450 μl/h) were evaluated. Participants/materials, setting, methods Ejaculates were evaluated by standard semen analysis according to WHO 2021 criteria. Following complete liquefaction, 1 mL of sample was used for DGC, and 0.8 mL of semen was used for the prototype MFSS at 0.2 mL for each flow rate. SCF was assessed by TUNEL assay with a normal threshold of ≤ 15%. Fluorescent in situ hybridization (FISH) was performed using X- and Y-chromosome probes. Main results and the role of chance A total of 7 men (35.4±5 years) had the following semen parameters: volume of 3.3±2 mL, concentration of 76.7±33 x106/mL, 45.5±1% motility, and a normal morphology of 3.2±0%. When comparing the post-processing parameters between the two methods, DGC yielded a concentration of 49.9±25 x106/mL and MFSS yielded a reduced concentration of 4.5±5x106/mL (P&amp;lt;0.0001). DGC yielded 91.1±1% motility and normal morphology of 3.2±0.4%. Albeit at a cost of concentration, MFSS yielded spermatozoa with significantly higher motility (96.3±3%; P&amp;lt;0.0001) and a higher proportion with normal morphology (4.0±0.6%; P&amp;lt;0.0001). Moreover, the SCF of the raw sample was 9.4±2.0%; although the SCF was 8.1±3.6% with DGC, it was 4.5±2% (P&amp;lt;0.001) with MFSS. An analysis was performed within the different flow rates of the MFSS; a 250 μl/h flow rate yielded the highest recovery rate (42.0±6%; P&amp;lt;0.001), highest concentration (5.6±4 x106/mL; P&amp;lt;0.01), highest motility (97.0±2.2%; P&amp;lt;0.05), and a normal morphology rate (4.3±1%). The SCF for this flow rate was &amp;lt;3%. Surprisingly, we noticed that the proportion of Y-chromosome–bearing spermatozoa positively correlated to the flow rate, suggesting that there may be a subtle difference in the kinetics of male and female spermatozoa. Limitations, reasons for caution Although our novel MFSS platform is a promising technique, it is costly and requires specific expertise and training. This is a limited observation and requires integration of clinical outcomes to prove its benefits. Wider implications of the findings A microfluidic device with a controlled flow rate allowed the fine-tuned selection of spermatozoa with superior hydrodynamic and kinetic characteristics and a higher genomic integrity. Once automated, this device may help to select spermatozoa with greater embryo developmental competence and be useful to isolate spermatozoa of the desired sex. Trial registration number N/A

O-166 Distinct molecular signatures of successful sperm in situ

Abstract Out of millions of ejaculated sperm, a few reach the fertilization site in mammals. Flagellar Ca2+ signaling nanodomains, organized by multi-subunit CatSper calcium channel complexes, are pivotal for sperm migration in the female tract, implicating CatSper-dependent mechanisms in sperm selection. Here using biochemical and pharmacological studies, we demonstrate that CatSper1 is an O-linked glycosylated protein, undergoing capacitation-induced processing dependent on Ca2+ and phosphorylation cascades. CatSper1 processing correlates with protein tyrosine phosphorylation (pY) development in sperm cells capacitated in vitro and in vivo. Using 3D in situ molecular imaging and ANN-based automatic detection of sperm distributed along the cleared female tract, we demonstrate that spermatozoa past the utero-tubal junction possess the intact CatSper1 signals. Together, we reveal that fertilizing mouse spermatozoa in situ are characterized by intact CatSper channel, lack of pY, and reacted acrosomes. These findings provide molecular insight into sperm selection for successful fertilization in the female reproductive tract.

Mating modifies the expression of crucial oxidative-reductive transcripts in the pig oviductal sperm reservoir: is the female ensuring sperm survival?

Mating induces large changes in the female genital tract, warranting female homeostasis and immune preparation for pregnancy, including the preservation of crucial oxidative status among its pathways. Being highly susceptible to oxidative stress, sperm survival and preserved function depend on the seminal plasma, a protection that is removed during sperm handling but also after mating when spermatozoa enter the oviduct. Therefore, it is pertinent to consider that the female sperm reservoir takes up this protection, providing a suitable environment for sperm viability. These aspects have not been explored despite the increasing strategies in modulating the female status through diet control and nutritional supplementation. To test the hypothesis that mating modifies the expression of crucial oxidative-reductive transcripts across the entire pig female genital tract (cervix to infundibulum) and, particularly in the sperm reservoir at the utero-tubal junction, before ovulation, a period dominated by estrogen stimulation of ovarian as well as of seminal origin. The differential expression of estrogen (ER) and progesterone (PR) receptors and of 59 oxidative-reductive transcripts were studied using a species-specific microarray platform, in specific segments of the peri-ovulatory sow reproductive tract in response to mating. Mating induced changes along the entire tract, with a conspicuous downregulation of both ER and PR and an upregulation of superoxide dismutase 1 (SOD1), glutaredoxin (GLRX3), and peroxiredoxin 1 and 3 (PRDX1, PRDX3), among other NADH Dehydrogenase Ubiquinone Flavoproteins, in the distal uterus segment. These changes perhaps helped prevent oxidative stress in the area adjacent to the sperm reservoir at the utero-tubal junction. Concomitantly, there were a downregulation of catalase (CAT) and NADH dehydrogenase (ubiquinone) oxidoreductases 1 beta subcomplex, subunit 1 (NDUFB1) in the utero-tubal junction alongside an overall downregulation of CAT, SOD1, and PRDX3 in the ampullar and infundibulum segments. Natural mating is an inducer of changes in the expression of female genes commanding antioxidant enzymes relevant for sperm survival during sperm transport, under predominant estrogen influence through the bloodstream and semen. The findings could contribute to the design of new therapeutics for the female to improve oxidative-reductive balance.

Multidisciplinary approach to the surgical management of interstitial ectopic pregnancy

To present a multidisciplinary approach to localize and resect suspected interstitial ectopic pregnancies. Interstitial ectopic pregnancies are distinct from eccentric intracavitary pregnancies and are defined by ultrasound-based criteria, including an empty uterine cavity, gestational sac located >1 cm from the cavity, thin overlying myometrium <5 mm, and the interstitial line sign. Case report. Academic medical center. Here, we present the case of a 28-year-old patient at 6 weeks of gestation by last menstrual period who presented to the emergency department with spotting. Initial pelvic ultrasound findings demonstrated a gestational sac and yolk sac that were believed to be located eccentrically within the uterine cavity. Follow-up imaging was performed 2 weeks later that revealed the pregnancy was located at the uterotubal junction and distinct from the endometrial cavity, consistent with an interstitial ectopic. The patient had ongoing light spotting with mild cramping, a benign clinical exam, and normal laboratory findings. Accurate assessment of pregnancy location is critical given that the mortality rate from interstitial pregnancies is twice that of other ectopics. In contrast, live birth rates for eccentric intracavitary pregnancies may be up to 69%, and some clinicians consider expectant management of asymptomatic patients in the first trimester. The patient was recommended for inpatient admission with expedited surgical management of interstitial ectopic pregnancy. On laparoscopic entry, the pregnancy was not well-visualized because it did not deform the uterine serosa. We present a surgical approach to suspected interstitial ectopic pregnancy that is not well-visualized at the time of laparoscopy. The following principles are explored: the use of multiple minimally invasive modalities (laparoscopy and hysteroscopy) to perform a thorough evaluation of the pregnancy location; incorporation of intraoperative ultrasound; temporary vessel ligation and injection of intramyometrial vasopressin; complete enucleation of the products of conception; and closure of the myometrial defect. We emphasize the benefits of a multidisciplinary approach for the localization and resection of interstitial ectopic pregnancy. This patient was discharged home in good condition with no complications.

A Cautionary Tale of the Tubal Stump

A 22 year-old G2A1 female, with a history of prior right salpingectomy for a ruptured ectopic pregnancy, presented to hospital with diffuse abdominal pain and vaginal spotting. Her b-HCG was over 16 000 mIU/mL. A pelvic ultrasound demonstrated a gestational sac with a fetal pole at the right utero-tubal junction, outside of the endometrial cavity (Figure 1), suggesting a pregnancy contained in the interstitium of the tubal stump remnant. Laparoscopy confirmed imaging findings (Figure 2). Dilute vasopressin was injected into the adjacent myometrium. A transverse incision was made along the most dependent area of the interstitial pregnancy, the products of conception were expressed from the uterine cornua, tubal stump removed, and the defect repaired (Figure 3). Figure 2Laparoscopy confirms an interstitial ectopic pregnancy within the tubal stump from prior salpingectomy. View Large Image Figure Viewer Download Hi-res image Figure 3Image of the pelvis after removal of ectopic pregnancy and repair View Large Image Figure Viewer Download Hi-res image

The bovine uterine fluid proteome is more impacted by the stage of the estrous cycle than the proximity of the ovulating ovary in the periconception period

Uterine secretions provide a suitable environment for sperm selective migration during a couple of days preceding ovulation and for early embryo development before implantation. Our goal was to identify and quantify proteins in the bovine uterine fluid during the periovulatory period of the estrous cycle. Genital tracts with normal morphology were collected from adult cyclic Bos taurus females in a local slaughterhouse and classified into pre-ovulatory or post-ovulatory stages of cycle (around days 19–21 and 0–5 of cycle, respectively; n = 8 cows per stage) based on ovarian morphology. Proteins from uterine fluid collected from the utero-tubal junction to the base of each horn (four pools of two cows per condition) were analyzed by nanoLiquid Chromatography coupled with tandem Mass Spectrometry (nanoLC-MS/MS). A total of 1214 proteins were identified, of which 91% were shared between all conditions. Overall, 57% of proteins were predicted to be secreted and 17% were previously reported in uterine extracellular vesicles. Paired comparisons between uterine horns ipsilateral and contralateral to ovulation evidenced 12 differentially abundant proteins, including five at pre-ovulatory stage. Furthermore, 35 proteins differed in abundance between pre- and post-ovulatory stages, including 21 in the ipsilateral side of ovulation. Functional analysis of identified proteins demonstrated roles in binding, metabolism, cellular detoxification and the immune response. This study provides a valuable database of uterine proteins for functional studies on sperm physiology and early embryo development.

From a Passive Conduit to Highly Dynamic Organ. What are the Roles of Uterine Tube Epithelium in Reproduction?

It is well known that the mammalian uterine tube (UT) plays a crucial role in female fertility, where the most important events leading to successful fertilization and pre-implantation embryo development occur. The known functions of these small intra-abdominal organs are: an uptake and transport of oocytes; storage, transportation, and capacitation of spermatozoa, and finally fertilization and transport of the fertilized ovum and early embryo through the isthmus towards the uterotubal junction. The success of all these events depends on the interaction between the uterine tube epithelium (UTE) and gametes/embryo. Besides that, contemporary research revealed that the tubal epithelium provides essential nutritional support and the most suitable environment for early embryo development. Moreover, recent discoveries in molecular biology help understand the role of the epithelium at the cellular and molecular levels, highlighting the factors involved in regulating the UT signaling, that affects different steps in the fertilization process. According to the latest research, the extracellular vesicles, as a major component of tubal secretion, mediate the interaction between gametes/embryo and epithelium. This review aims to provide up-to-date knowledge on various aspects concerning tubal epithelium activity and its cross-talk with spermatozoa, oocytes and preimplantation embryo and how these interactions affect fertilization and early embryo development.

Multidisciplinary Approach to the Surgical Management of Interstitial Ectopic Pregnancy

<h3>Study Objective</h3> We aim to present a multidisciplinary approach to localize and resect suspected interstitial ectopic pregnancy. <h3>Design</h3> Case report. <h3>Setting</h3> Academic medical center. <h3>Patients or Participants</h3> 28-year-old at 6 weeks gestation by last menstrual period presented to the emergency department with spotting. Although initial ultrasound suggested an eccentric intracavitary pregnancy, follow up imaging two weeks later showed that the pregnancy was located at the uterotubal junction, distinct from the endometrial cavity, and with thin overlying myometrium. This ruled in for suspected interstitial ectopic pregnancy. <h3>Interventions</h3> Given the patient's gestational age, vaginal spotting and pelvic pain, she was recommended to undergo surgical management. Upon laparoscopic entry, the pregnancy was not well visualized as it did not deform the uterine serosa. <h3>Measurements and Main Results</h3> We present a surgical approach to suspected interstitial ectopic pregnancy that is not well-visualized at the time of laparoscopy. The following principles are explored: 1) use of multiple minimally invasive modalities (laparoscopy and hysteroscopy) to perform thorough evaluation for pregnancy location, 2) incorporation of intraoperative ultrasound, 3) temporary vessel ligation and injection of intramyometrial vasopressin, 4) complete enucleation of products of conception, and 5) closure of the myometrial defect. <h3>Conclusion</h3> We emphasize the benefits of a multidisciplinary approach to localization and resection of interstitial ectopic pregnancy. This patient was discharged home in good condition with no complications.

TMPRSS12 Functions in Meiosis and Spermiogenesis and Is Required for Male Fertility in Mice.

Serine proteases are involved in many physiological activities as initiators of proteolytic cascades, and some members have been reported to play roles in male reproduction. Transmembrane serine protease 12 (TMPRSS12) has been shown to regulate sperm motility and uterotubal junction migration in mice, but its role in the testis remains unknown. In this study, we verified that TMPRSS12 was expressed in the spermatocytes and spermatids of testis and the acrosome of sperm. Mice deficient in Tmprss12 exhibited male sterility. In meiosis, TMPRSS12 was demonstrated to regulate synapsis and double-strand break repair; spermatocytes of Tmprss12 −/− mice underwent impaired meiosis and subsequent apoptosis, resulting in reduced sperm counts. During spermiogenesis, TMPRSS12 was found to function in the development of mitochondria; abnormal mitochondrial structure in Tmprss12 −/− sperm led to reduced availability of ATP, impacting sperm motility. The differential protein expression profiles of testes in Tmprss12 −/− and wild-type mice and further molecule identification revealed potential targets of TMPRSS12 related to meiosis and mitochondrial function. Besides, TMPRSS12 was also found to be involved in a series of sperm functions, including capacitation, acrosome reaction and sperm-egg interaction. These data imply that TMPRSS12 plays a role in multiple aspects of male reproduction.

Using MRI to differentiate upper-lateral intracavitary pregnancy and interstitial pregnancy for the patients with pregnancies in the uterotubal junction during the first trimester

ObjectivesTo retrospectively evaluate the diagnostic value of MRI for the uterotubal junctional pregnancies during the first trimester.MethodsThis retrospective study involved 59 patients (January 2016 to July 2021) with a preoperative imaging diagnosis of uterotubal junctional pregnancy. Using operative and pathological reports as the reference standard, we identified 22 patients with upper-lateral intracavitary (angular) pregnancy and 37 patients with interstitial pregnancy. Two senior radiologists, blinded to the patients’ information, reviewed the MRI images and determined each MRI feature based on the original interpretation criteria. Any disagreement was resolved by discussion to achieve a consensus. The sensitivity and specificity of each MRI feature were calculated according to the reference standard.ResultsThe endometrial thickness in the upper-lateral intracavitary pregnancy group was larger than in the interstitial group (p = 0.001). The cutoff value of the endometrial thickness was 11.5 mm with a sensitivity, specificity, and area under the curve that were 77.3%, 64.9%, and 0.743, respectively. Two key features to diagnose upper-lateral intracavitary pregnancy were “medial free edge” and “medial free edge plus above-cutoff endometrial thickness.” The sensitivity and specificity of the medial free edge were 100% and 94.9%, respectively. The sensitivity and specificity of the medial free edge plus above-cutoff endometrial thickness were 77.3% and 100%, respectively. The key feature to diagnose interstitial pregnancy was an “intact lateral junctional zone,” of which the sensitivity and specificity were 94.6% and 100%, respectively.ConclusionsMRI can be used to differentiate the upper-lateral intracavitary pregnancy and interstitial pregnancy during the first trimester.Key Points• We demonstrated MRI diagnostic criteria for the interstitial pregnancy and upper-lateral intracavitary pregnancy.• MRI might be used to identify the complex interstitial pregnancies, those with a gestational sac protruding into the uterine cavity.

Semen Modulates Cell Proliferation and Differentiation-Related Transcripts in the Pig Peri-Ovulatory Endometrium.

Simple SummaryHomeostasis of the uterus after mating is crucial for the subsequent reproductive events. The post-mating inflammatory response is restricted to the uterus, but semen also modulates the expression of other genes involved in regulation along the female reproductive tract, including the oviduct. This study aims to determine if several ejaculate fractions of the pig may modulate cell proliferation and differentiation-related transcripts in different sections of the peri-ovulatory sow reproductive tract. Our data demonstrate that most of the mRNA expression changes of the 144 transcripts tested were induced by mating. Additionally, spermatozoa and seminal plasma also triggered differential expression of the transcripts tested. Finally, our data imply that spermatozoa, seminal plasma components, and the act of mating induce differential mechanisms in the peri-ovulatory female reproductive tract, which are essential for tissue repair.Uterine homeostasis is maintained after mating by eliminating pathogens, foreign cells, and proteins by a transient inflammation of the uterus. Such inflammation does not occur in the oviductal sperm reservoir (utero-tubal junction, UTJ), colonized by a population of potentially fertile spermatozoa before the inflammatory changes are triggered. Semen entry (spermatozoa and/or seminal plasma) modifies the expression of regulatory genes, including cell proliferation and differentiation-related transcripts. Considering pigs display a fractionated ejaculation, this study aims to determine whether different ejaculate fractions differentially modulate cell proliferation and differentiation-related transcripts in the sow reproductive tract during the peri-ovulatory stage. Using species-specific microarray analyses, the differential expression of 144 cell proliferation and differentiation-related transcripts was studied in specific segments: cervix (Cvx), distal and proximal uterus (DistUt, ProxUt), UTJ, isthmus (Isth), ampulla (Amp), and infundibulum (Inf) of the peri-ovulatory sow reproductive tract in response to semen and/or seminal plasma cervical deposition. Most mRNA expression changes were induced by mating. In addition, while mating upregulates the fibroblast growth factor 1 (FGF1, p-value DistUt = 0.0007; ProxUt = 0.0253) transcript in the endometrium, both its receptor, the fibroblast growth factor receptor 1 (FGFR1, p-value DistUt = 2.14 e−06; ProxUt = 0.0027; UTJ = 0.0458) transcript, and a potentiator of its biological effect, the fibroblast growth factor binding protein 1 (FGFBP1), were downregulated in the endometrium (p-value DistUt = 0.0068; ProxUt = 0.0011) and the UTJ (p-value UTJ = 0.0191). The FGFBP1 was downregulated in the whole oviduct after seminal depositions (p-value Isth = 0.0007; Amp = 0.0007; Inf = 6.87 e−05) and, interestingly, FGFR1 was downregulated in the endometrium in the absence of semen (p-value DistUt = 0.0097; ProxUt = 0.0456). In conclusion, the findings suggest that spermatozoa, seminal components, and the act of mating trigger, besides inflammation, differential mechanisms in the peri-ovulatory female reproductive tract, relevant for tissue repair.