Female Reproductive Tissues Research Articles

Regional specialization, polyploidy, and seminal fluid transcripts in the Drosophila female reproductive tract

Sexual reproduction requires the choreographed interaction of female cells and molecules with sperm and seminal fluid. In internally fertilizing animals, these interactions are managed by specialized tissues within the female reproductive tract (FRT), such as a uterus, glands, and sperm storage organs. However, female somatic reproductive tissues remain understudied, hindering insight into the molecular interactions that support fertility. Here, we report the identification, molecular characterization, and analysis of cell types throughout the somatic FRT in the premier Drosophila melanogaster model system. We find that the uterine epithelia is composed of 11 distinct cell types with well-delineated spatial domains, likely corresponding to functionally specialized surfaces that interact with gametes and reproductive fluids. Polyploidy is pervasive: More than half of lower reproductive tract cells are ≥4C. While seminal fluid proteins (SFPs) are typically thought of as male products that are transferred to females, we find that specialized cell types in the sperm storage organs heavily invest in expressing SFP genes. Rates of amino acid divergence between closely related species indicate heterogeneous evolutionary processes acting on male-limited versus female-expressed seminal fluid genes. Together, our results emphasize that more than 40% of annotated seminal fluid genes are better described as shared components of reproductive transcriptomes, which may function cooperatively to support spermatozoa. More broadly, our work provides the molecular foundation for improved technologies to catalyze the functional characterization of the FRT.

COVID-19 and Reproductive Function: A Detailed Review of Fertility Outcomes, Sperm Alterations, and Vertical Transmission Concerns

Background:The global COVID-19 pandemic, caused by SARS-CoV-2, raises concerns about its effects on reproductive health. Emerging evidence suggests potential impacts on male and female fertility, including hormonal changes, immune responses, and organ damage, though the virus’s direct influence on reproductive tissues and vertical transmission remains unclear. Objective:This review summarizes current evidence on COVID-19’s effects on male and female reproductive health, focusing on sperm count, fertility, and vertical transmission. Methods:A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Peer-reviewed studies were included based on their relevance to reproductive outcomes, sperm count, hormonal changes, and vertical transmission of SARS-CoV-2. Results:Most studies found no direct evidence of SARS-CoV-2 in male or female reproductive tissues. However, a temporary decline in sperm count and quality has been reported in men recovering from COVID-19. Hormonal fluctuations, particularly increased luteinizing hormone (LH) levels, were observed in some male patients. In females, the presence of ACE2 receptors in reproductive organs suggests a potential risk, but no conclusive evidence of impaired fertility has been found. Vertical transmission remains uncertain, with isolated cases reporting elevated IgM antibodies in newborns. Conclusion:Although direct evidence of SARS-CoV-2 impacting fertility is limited, temporary reproductive disruptions in males, including reduced sperm count, have been noted. The risk of vertical transmission remains unclear. Further research is essential to determine COVID-19’s long-term reproductive effects.

Eight hydroxyproline-O-galactosyltransferases play essential roles in female reproductive development

In angiosperms, ovules give rise to seeds upon fertilization. Thus, seed formation is dependent on both successful ovule development and tightly controlled communication between female and male gametophytes. During establishment of these interactions, cell walls play a pivotal role, especially arabinogalactan-proteins (AGPs). AGPs are highly glycosylated proteins decorated by arabinogalactan side chains, representing 90 % of the AGP molecule. AGP glycosylation is initiated by a reaction catalysed by hydroxyproline-O-galactosyltransferases (Hyp-GALTs), specifically eight of them (GALT2–9), which add the first galactose to Hyp residues. Five Hyp-GALTs (GALT2, 5, 7, 8 and 9) were previously described as essential for AGP functions in pollen and ovule development, pollen-pistil interactions, and seed morphology. In the present work, a higher order Hyp-GALT mutant (23456789) was studied, with a high degree of under-glycosylated AGPs, to gain deeper insight into the crucial roles of these eight enzymes in female reproductive tissues. Notably, the 23456789 mutant demonstrated a high quantity of unfertilized ovules, displaying abnormal callose accumulation both at the micropylar region and, sometimes, throughout the entire embryo sac. Additionally, this mutant displayed ovules with abnormal embryo sacs, had a disrupted spatiotemporal distribution of AGPs in female reproductive tissues, and showed abnormal seed and embryo development, concomitant with a reduction in AGP-GlcA levels. This study revealed that at least three more enzymes exhibit Hyp-O-GALT activity in Arabidopsis (GALT3, 4 and 6), and reinforces the crucial importance of AGP carbohydrates in carrying out the biological functions of AGPs during plant reproduction.

P-290 Isolation and characterization of extracellular vesicles from human endometrial organoids

Abstract Study question Do human endometrial organoids produce extracellular vesicles (EVs)? Summary answer Endometrial organoids release EVs (ORG-EVs) that we successfully and comprehensively characterize according to guidelines. What is known already EVs play a crucial role in cellular communication, garnering increasing attention in physiological and pathological processes. Although the enormous potential of EVs has been extensively demonstrated across a large variety of research fields, the promise held by EVs derived from human endometrial organoids is still largely unexplored. Indeed, nowadays there is limited research available on the presence, role, and function of EVs derived from organoids of female reproductive tissue samples. This underscores the importance of adopting standardized methods for isolating, characterizing, and reporting findings, which is crucial for advancing in this promising and innovative, yet challenging, research field. Study design, size, duration This study involved establishing organoid cultures from endometrial biopsies of healthy women (n = 10) of reproductive age, who underwent ovarian surgery between January and October 2023. ORG-EVs were isolated using differential ultracentrifugation. Characterization of ORG-EVs, including assessment of their biophysical and biochemical properties, adhered to guidelines established by the International Society for Extracellular Vesicles (ISEV). Participants/materials, setting, methods Endometrial specimens from 10 women were employed to establish organoid cultures. ORG-EVs were isolated from spent medium through differential ultracentrifugation. Morphology, size distribution and concentration analysis were performed using Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA). Western blotting was used to confirm the presence of EVs markers. Main results and the role of chance TEM analysis confirmed the presence of isolated ORG-EVs, elucidating their morphology and structural integrity. NTA revealed that ORG-EVs had an average size of 160.4 ± 6.2 nm (mean ± SD) and a mean concentration of 5.2E+11 ± 2.1E+10 particles/ml (mean ± SD). Western blot analysis further confirmed the vesicular nature of the assessed particles, demonstrating positivity for standard EV markers such as tetraspanins (CD63 and CD9), and soluble proteins (ALIX and TSG101), while excluding the endoplasmic reticulum-resident protein calnexin (negative control). Additionally, ORG-EVs exhibited a positive signal for mucin1 (MUC1), a glycoprotein present on the surface of endometrial epithelial cells, thereby confirming their cellular origin. Limitations, reasons for caution This is a pilot study, characterized by a small sample size requiring larger cohorts to validate results and, at the same time, to undertake deeper exploration of ORG-EVs’ molecular cargo. Emphasizing the critical need for standardized isolation and characterization methods is paramount. Wider implications of the findings Endometrial organoids enhance EVs production, providing a powerful tool for reproductive aspects studies, and improving regenerative medicine and artificial reproductive technology. These initial findings propel further exploration, unveiling of ORG-EVs’ molecular cargo aiming to elucidate their potential role in human female reproductive tissues and mechanism related to embryo implantation process. Trial registration number not applicable

Hydrogen sulfide and its role in female reproduction.

Hydrogen sulfide (H2S) is a gaseous signaling molecule produced in the body by three enzymes: cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S is crucial in various physiological processes associated with female mammalian reproduction. These include estrus cycle, oocyte maturation, oocyte aging, ovulation, embryo transport and early embryo development, the development of the placenta and fetal membranes, pregnancy, and the initiation of labor. Despite the confirmed presence of H2S-producing enzymes in all female reproductive tissues, as described in this review, the exact mechanisms of H2S action in these tissues remain in most cases unclear. Therefore, this review aims to summarize the knowledge about the presence and effects of H2S in these tissues and outline possible signaling pathways that mediate these effects. Understanding these pathways may lead to the development of new therapeutic strategies in the field of women's health and perinatal medicine.

Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model.

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female FVB/N mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor.

Abrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery. This second study had 4 groups of 20 females each administered abrocitinib (0, 3, 10, or 70 mg/kg/day) 2 weeks prior to cohabitation through gestation day (GD) 7. In addition, 2 groups of 20 rats (0 or 70 mg/kg/day) were dosed for 3 weeks followed by a 4-week recovery period before mating. All mated females were evaluated on GD 14. No effects were observed at ≤10 mg/kg/day. At 70 mg/kg/day (29x human exposure), decreased pregnancy rate, implantation sites, and viable embryos were observed. All these effects reversed 4 weeks after the last dose. Based on these data and literature on the potential role of JAK signaling in implantation, we hypothesize that these effects may be related to JAK1 inhibition and, generally, that peri-implantation effects such as these, in the absence of cycling or microscopic changes in nonpregnant female reproductive tissues, are anticipated to be reversible.

Tissue-specific gene expression of genome-wide significant loci associated with major depressive disorder subtypes

Major depressive disorder (MDD) is a clinically and genetically heterogeneous disorder. To reduce heterogeneity, large-scale genome-wide association studies have recently identified genome-wide significant loci associated with seven MDD subtypes. However, it was unclear in which tissues the genes near those loci are specifically expressed. We investigated whether genes related to specific MDD subtypes would be preferably expressed in a specific tissue. At 14 novel subtype-specific loci related to seven MDD subtypes—(1) non-atypical-like features MDD, (2) early-onset MDD, (3) recurrent MDD, (4) MDD with suicidal thoughts, (5) MDD without suicidal thoughts, (6) MDD with moderate impairment, and (7) postpartum depression, we investigated whether 22 genome-wide significant genetic variant-mapped genes were tissue-specifically expressed in brain, female reproductive, male specific, cardiovascular, gastrointestinal, or urinary tissues in the Genotype-Tissue Expression (GTEx) subjects (n ≤ 948). To confirm the tissue-specific expression in the GTEx, we used independent Human Protein Atlas (HPA) RNA-seq subjects (n ≤ 95). Of 22 genes, nine and five genes were tissue-specifically expressed in brain and female reproductive tissues, respectively (p < 2.27 × 10−3). RTN1, ERBB4, and AMIGO1 related to early-onset MDD, recurrent MDD, or MDD with suicidal thoughts were highly expressed in brain tissues (d = 1.19–2.71), while OAS1, LRRC9, DHRS7, PSMA5, SYPL2, and GULP1 related to non-atypical-like features MDD, early-onset MDD, MDD with suicidal thoughts, or postpartum depression were expressed at low levels in brain tissues (d = −0.17−−1.48). DFNA5, CTBP2, PCNX4, SDCCAG8, and GULP1, which are related to early-onset MDD, MDD with moderate impairment, or postpartum depression, were highly expressed in female reproductive tissues (d = 0.80–2.08). Brain and female reproductive tissue-specific expression was confirmed in the HPA RNA-seq subjects. Our findings suggest that brain and female reproductive tissue-specific expression might contribute to the pathogenesis of MDD subtypes.

Effects of the Neuropeptides Pituitary Adenylate Cyclase Activating Polypeptide and Vasoactive Intestinal Peptide in Male Fertility.

Background and Objectives: The neuroendocrine system plays a crucial role in regulating various bodily functions, including reproduction, with evidence suggesting its significant involvement in male fertility and sperm development. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are expressed in both male and female reproductive tissues, influencing penile erection and regulating steroidogenesis in males. Therefore, our study aimed to compare the protein levels of VIP and PACAP in seminal plasma between healthy controls and sub-fertile patients. Additionally, we sought to correlate the levels of these biomarkers with clinical, functional, and laboratory findings in the participants. Materials and Methods: The study included a total of 163 male participants for analysis. The participants were further stratified into subgroups of fertile and sub-fertile men of four subgroups according to the 2021 WHO guidelines. Seminal plasma concentrations of the neuropeptides VIP and PACAP were measured using human enzyme-linked immunosorbent assay technique. Results: The findings showed statistically significant differences in total sperm count, sperm concentration, total motility, and vitality (p < 0.001) between the fertile group and the sub-fertile group. Specifically, significant differences found between healthy males and oligoasthenospermic patients (p = 0.002), and between asthenospermic and oligoasthenospermic patients (p = 0.039). An ROC analysis showed associated sensitivity and specificity values of 62.2% and 55.6%, respectively, to PACAP seminal levels differentiated between sub-fertile patients from fertile males (p = 0.028). No significant difference in seminal levels of VIP was found between the sub-fertile and fertile groups. Conclusions: Previous research leads to the point of PACAP active involvement in spermatogenesis. In accordance to our study, in human semen samples, we have seen a significance change in PACAP levels amongst patients with low sperm count or with both low sperm count and low motility, hinting at its contribution and acting as a possible factor in this complex process. Thus, alterations in the levels or actions of these neuropeptides have been associated with certain reproductive disorders in males.

Walking a thin line between fixation and epitope binding - characterization of antigen retrieval methods suitable for eosinophil and HSV-2 staining in formalin-fixed female reproductive tissue.

Antibody-based fluorescence analysis of female reproductive tissues in research of sexually transmitted diseases allows for an in-depth understanding of protein localization, interactions, and pathogenesis. However, in many cases, cryosectioning is not compatible with biosafety regulations; at all times, exposure of lab personnel and the public to potentially harmful pathogens from biological infectious material must be avoided; thus, formaldehyde fixation is essential. Due to formaldehyde's cross-linking properties, protein detection with antibodies can be impeded. To allow effective epitope binding during immunofluorescence of formalin-fixed paraffin-embedded vaginal tissue, we investigated two antigen retrieval methods. We tested these methods regarding their suitability for automated image analysis, facilitating reproducible quantitative microscopic data acquisition in sexually transmitted disease research. Heat-based retrieval at 80°C in citrate buffer proved to increase antibody binding to eosinophil protein and HSV-2 visibly and tissue morphology best, and was the most efficient for sample processing and quantitative analysis.

Mueller matrix polarization interferometry of optically anisotropic architectonics of biological tissue object fields: the fundamental and applied aspects

The presented results concern the diagnostic application of vector-parameter polarization mapping and polarization-interference phase scanning applied to layered azimuths and ellipticity polarization maps obtained with the help of digital holographic reproduction for phase-inhomogeneous tissue layers in the female reproductive system. The differential diagnosis of the pathological changes in optically anisotropic polycrystalline tissue components, specifically “benign (fibroids) and precancerous (endometriosis),” was investigated. All studies within the representative groups of the histological samples were conducted using circularly polarized laser radiation, ensuring azimuthal invariance and polarization measurement reliability. Integral and layered maps and polarization azimuths and ellipticity random variable distribution histograms were obtained from the microscopic images of histological sections from the female reproductive system tumors. Systematized tables present statistical moments which characterize azimuths and ellipticity polarization maps for fibroids and endometriosis tissues. It is shown that the statistical parameters (diagnostic markers) are the most sensitive to benign and precancerous changes in the female reproductive system tissues. The results of information analysis, including the accuracy determination of the diagnostic vector-parameter polarization and polarization-interference methods for detecting and differentiating the samples of fibroids and precancerous endometriosis tissues in the female reproductive system, are presented.

Background and common lesions in the female reproductive organs of giant anteaters (Myrmecophaga tridactyla).

The giant anteater (Myrmecophaga tridactyla) is a vulnerable species in South America and is considered endangered or near extinction in Central America. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of the female reproductive tissues of this species. We collected tissue samples from six female giant anteaters and performed gross, morphological, and histochemical analyses. Five adult subjects and one juvenile were included in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

Differential expression and evolutionary diversification of RNA helicases in Boechera sexual and apomictic reproduction.

In higher plants, sexual reproduction is characterized by meiosis of the first cells of the germlines, and double fertilization of the egg and central cell after gametogenesis. In contrast, in apomicts of the genus Boechera, meiosis is omitted or altered and only the central cell requires fertilization, while the embryo forms parthenogenetically from the egg cell. To deepen the understanding of the transcriptional basis underlying these differences, we applied RNA-seq to compare expression in reproductive tissues of different Boechera accessions. This confirmed previous evidence of an enrichment of RNA helicases in plant germlines. Furthermore, few RNA helicases were differentially expressed in female reproductive ovule tissues harboring mature gametophytes from apomictic and sexual accessions. For some of these genes, we further found evidence for a complex recent evolutionary history. This included a homolog of Arabidopsis thaliana FASCIATED STEM4 (FAS4). In contrast to AtFAS4, which is a single-copy gene, FAS4 is represented by three homologs in Boechera, suggesting a potential for subfunctionalization to modulate reproductive development. To gain first insights into functional roles of FAS4, we studied Arabidopsis lines carrying mutant alleles. This identified the crucial importance of AtFAS4 for reproduction, as we observed developmental defects and arrest during male and female gametogenesis.

Interaction of semen with female reproductive tract tissues: what we know, what we guess and what we need to do.

For nearly 100 years the postcoital inflammatory response has been described in the female reproductive tract of rodents. Since the 1950's this observation has been made in a number of animals including humans and domestic species. Yet pregnancy can be initiated and maintained by using embryo transfer which bypasses insemination and the related postcoital inflammatory response. Thus, the role of semen exposure beyond sperm transport and subsequent postcoital inflammatory response in female reproductive tissues has yet to be given a true physiological purpose. Historically the postcoital inflammatory response of female tissues was suggested to remove spermatozoa and male derived pathogens from the female reproductive tract. More recently, semen exposure and the postcoital inflammatory response have been suggested to play a role in long-term preparation of the maternal immune system to the semi-allogeneic pregnancy, ancillary support of the preimplantation embryo, and potentially fetal programing that improves pregnancy outcomes, while the absence or inappropriate postcoital inflammation has been suggested to contribute to pregnancy complications. Although the postcoital inflammatory response has been robustly characterized, the evidence for its role in promoting positive pregnancy outcomes or reducing pregnancy complications remains tenuous. This manuscript is designed to balance the information we know regarding semen exposure and postcoital inflammation in various animal systems, with the information we perceive to be factual but perhaps not yet fully tested, along with the data we have yet to generate if we intend to postulate a physiological purpose of the postcoital inflammatory response to pregnancy outcomes.

Icariin, A Novel Promising Complementary Therapeutic Strategy in the Management of Female Infertility: A Literature Review:.

The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids’ receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of Icariin on female infertility for the firs time.

Comprehensive analysis and immunohistochemistry localization of NRP1 expression in pancancer and normal individual tissues in relation to SARS‑CoV‑2 susceptibility.

Neuropilin 1 (NRP1/CD304) is a typical membrane-bound co-receptor for vascular endothelial growth factor, semaphorin family members and viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, NRP1 expression levels across cancer types and the potential role of SARS-CoV-2 infection in patients with cancer are not clear. Online databases, such as The Cancer Genome Atlas database of Human Protein Atlas, Gene Expression Profiling Interactive Analysis and cBioPortal were used for the expression analysis in this study. Immunohistochemical (IHC) staining for NRP1 was performed in the tissues of patients with non-small cell carcinoma. As a result, it was found that NRP1 mRNA and protein expression levels were highest in the female reproductive tissues and the respiratory system, specifically in the nasopharynx, bronchus and fallopian tube, as well as in adipocytes, hepatic stellate cells, Sertoli cells, endothelial cells and dendritic cells. IHC showed that the NRP1 protein was mainly localized to the cytoplasm and membrane in the tissues of patients with non-small cell carcinoma, demonstrating its role in lung infection by SARS-CoV-2, due to invasion of cell membranes by the virus. Levels of NRP1 mRNA were significantly increased in lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma, stomach adenocarcinoma and thymoma, and significantly decreased in cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney chromophobe, lung squamous cell carcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma, compared with corresponding healthy tissues in pancancer, indicating roles for viral invasion in most cancer types. Moreover, low NRP1 expression was significantly associated with long overall survival (OS) time in adrenocortical carcinoma, brain lower grade glioma, stomach adenocarcinoma and uveal melanoma, but with short OS time in KIRC only. The ENST00000374867.6 (NRP1-202) isoform is most highly expressed in most cancer types and thus could be involved in tumorigenesis and SARS-CoV-2 invasion in cancer patients. NRP1 may be involved in SARS-CoV-2 invasion in patients with cancer, including those with lung cancer.

Convergent rates of protein evolution identify novel targets of sexual selection in primates.

Sexual selection is the differential reproductive success of individuals, resulting from competition for mates, mate choice, or success in fertilization. In primates, this selective pressure often leads to the development of exaggerated traits which play a role in sexual competition and successful reproduction. In order to gain insight into the mechanisms driving the development of sexually selected traits, we used an unbiased genome-wide approach across 21 primate species to correlate individual rates of protein evolution to relative testes size and sexual dimorphism in body size, 2 anatomical hallmarks of sexual selection in mammals. Among species with presumed high levels of sperm competition, we detected strong conservation of testes-specific proteins responsible for spermatogenesis and ciliary form and function. In contrast, we identified accelerated evolution of female reproductive proteins expressed in the vagina, cervix, and fallopian tubes in these same species. Additionally, we found accelerated protein evolution in lymphoid tissue, indicating that adaptive immune functions may also be influenced by sexual selection. This study demonstrates the distinct complexity of sexual selection in primates revealing contrasting patterns of protein evolution between male and female reproductive tissues.

Evidences of differential methylation in the genome during development in the cactophilic Drosophila species.

DNA methylation with 5-methylcytosine (5mC) has been reported in the genome of several eukaryotes, with marked differences between vertebrates and invertebrates. DNA methylation is poorly understood as its role in evolution in insects. Drosophila gouveai (cluster Drosophila buzzatii) presents larvae that develop obligatorily in necrotic tissues of cacti in nature, with the distribution of populations in South America, and plasticity of phenotypes in insect-plant interaction. We characterize organisms at developmental stages and analyze variations at multiple methylation-sensitive loci in pupae, and adult flies using methylation sensitive amplification polymorphism. We obtained 326 loci with CCGG targets in the genome of D. gouveai. Genomic regions with molecular lengths from 100 to 700 pb were most informative about methylation states. Multiple loci show differences in methylation-sensitive sites (MSL) concerning developmental stages, such as in pupae (MSL = 40), female reproductive tissue (MSL = 76), and male reproductive tissues (MSL = 58). Our results are the first evidence of genome-wide methylation in D. gouveai organisms.

Early-life exposure to acephate inhibits sexual development and induces testicular and ovarian toxicity in mice

Acephate is an organophosphate insecticide that exerts its toxicity by acting on the nervous system of insects. In addition to its action on the mammalian nervous system, acephate can also induce endocrine disruption of the reproductive system in mammals. However, the effects of acephate on sexual maturation and ovary development remain unclear. This study evaluated whether early-life exposure to acephate negatively impacts the male and female sexual maturation process and mature reproductive tissues. C57BL/6N mice were exposed to acephate (0, 0.3, 300 ppm) in drinking water from embryonic day 11.5 to ablactation, when the pups were four weeks old. Both sexes in the high-dose group experienced an early postnatal growth deficit, while females in the low-dose group continued to gain weight until 10 weeks of age. Exposure to acephate altered the anogenital index in females. Furthermore, preputial separation and vaginal opening were delayed in the high-dose group. At maturity, the weight of the seminal vesicles was decreased in the high-dose group. All treated groups exhibited increased vacuolation, accumulation of residual bodies, and degeneration in the testes. Furthermore, follicle regression was observed, and the healthy follicle number at each developmental stage was decreased in all treated groups. These results are probably due to the inhibition of the regulation by the hypothalamic-pituitary-gonadal axis and direct toxicity to reproductive organs. In conclusion, our study demonstrates that early-life exposure to acephate in mice may disrupt normal postnatal development, postpone puberty onset, and adversely affect reproductive functions during the reproductive period in both sexes.

Chromatin architectural factor CTCF is essential for progesterone-dependent uterine maturation.

Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes. Loss-of-function CTCF mutation in >20% of human endometrial tumors indicates its importance in uterine homeostasis. To better understand how CTCF-mediated enhancer-gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcfd/d uterine tissue exhibited a marked reduction in the number of uterine glands compared to those without Ctcf deletion (Ctcff/f mice). Post-pubertal Ctcfd/d uteri were hypoplastic with significant reduction in both the amount of the endometrial stroma and number of glands. Transcriptional profiling revealed increased expression of stem cell molecules Lif, EOMES, and Lgr5, and enhanced inflammation pathways following Ctcf deletion. Analysis of the response of the uterus to steroid hormone stimulation showed that CTCF deletion affects a subset of progesterone-responsive genes. This finding indicates (1) Progesterone-mediated signaling remains functional following Ctcf deletion and (2) certain progesterone-regulated genes are sensitive to Ctcf deletion, suggesting they depend on gene-enhancer interactions that require CTCF. The progesterone-responsive genes altered by CTCF ablation included Ihh, Fst, and Errfi1. CTCF-dependent progesterone-responsive uterine genes enhance critical processes including anti-tumorigenesis, which is relevant to the known effectiveness of progesterone in inhibiting progression of early-stage endometrial tumors. Overall, our findings reveal that uterine Ctcf plays a key role in progesterone-dependent expression of uterine genes underlying optimal post-pubertal uterine development.