Iván Bahena

Parabens are synthetic chemicals that, due to their antibacterial and fungicidal effects, are widely used as preservatives in food, cosmetics, and personal care products, such as shampoos, hair conditioners, body creams, soaps, deodorants, makeup, wet wipes, lotions, female hygiene products, and vaginal lubricants. Several years ago, they were considered noncytotoxic, but studies have since shown that parabens act as endocrine disruptors due to their similarity to estradiol and could interfere with fertility. In recent decades, they have been associated with decreased fertility in the population. Although there are studies showing the effect of various parabens on reproduction, there are few related to the effect of propylparaben (PrPB) on oocyte maturation and embryo development. The present study aimed to evaluate the in vitro effect of PrPB on oocyte maturation and embryo development. The calculated lethal concentration (LC ₅₀ ) and concentration of inhibition of maturation (IM ₅₀ ) for both events was 140 μM. After 144 h post fertilization, the viability of developed embryos was reduced according to the PrPB increased. The total number of dividing embryos was classified from two blastomeres to late blastocyst. In all concentrations, there was embryo development, except in the concentration 300 μM, in which all were dead. The results of this study provide evidence that PrPB could affect female reproductive health by reducing oocyte maturation and delaying early embryo development. Therefore, further studies are required to explore the possible mechanisms producing the damage caused by the constant use of products containing PrPB.

Parabens (PBs) are compounds widely used as preservatives in personal care products, food, and pharmaceuticals. Methylparaben (MePB) is the most used by different industries due to its chemical properties and low cost. The high daily human exposure to these compounds has raised concerns about their potential effects on health, particularly on reproductive health. Therefore, the aim of this study was to evaluate the effect of the in vitro exposure of porcine oocytes to concentrations of 0, 500, 750, and 1000 μM MePB on the viability of cumulus cells (CCs) and oocytes; oocyte apoptosis and necrosis; DNA integrity of CCs; chromatin integrity of oocytes; maturation, fertilization, and embryo development competence; and embryo viability after in vitro production. The results showed that the viability of oocytes decreased significantly at 1000 μM concentration of MePB, and the viability of CCs decreased at the 750 μM concentration. MePB did not induce apoptosis or necrosis in oocytes. DNA damage in CCs increased at all concentrations tested, from 500 to 1000 μM, and chromatin damage in oocytes was observed at 1000 μM. In vitro oocyte maturation and embryo development rates decreased starting at 750 μM, and total embryo cleavage and viability decreased at 1000 μM. Reduced morulae and blastocyst formation were also observed. These findings suggest that MePB damages both CCs and oocytes, impairing their developmental competence and reducing the production of viable embryos. These findings contribute to understanding the potential effects of MePB on reproductive health and its possible link with fertility problems.

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, driven by late diagnosis, limited therapeutic options, and high metastatic potential. Beyond their canonical roles in hemostasis, platelets have emerged as active modulators of tumor progression and promising noninvasive biomarkers. Among platelet-associated molecules, α-defensins, particularly Defensin Alpha 1/3 (DEFA1/3), have been implicated in inflammation and immunity; however, their contribution to PDAC pathogenesis remains unclear. We combined bioinformatic analysis of platelet transcriptomes with functional and in vivo zebrafish xenograft validation to investigate the impact of DEFA1/3 on PDAC aggressiveness. DEFA1/3 was significantly upregulated in PDAC-derived platelets. Defensin-enriched platelet-like particles (defensin-rich platelets, DRPs) and recombinant DEFA1/3 enhanced pancreatic cancer cell proliferation, migration, and three-dimensional growth in vitro and promoted tumor dissemination in zebrafish xenografts. Transcriptomic profiling revealed the upregulation of SPARC, KDM6A, and GATA6, whereas clinical data from The Cancer Genome Atlas (TCGA)-PDAC linked high DEFA1/3 expression to poor survival, increased immune infiltration, and activation of epithelial–mesenchymal transition (EMT). Platelet-derived DEFA1/3 acts as a functional modulator of PDAC progression, linking platelet granule content to tumor aggressiveness and highlighting a potential biomarker and therapeutic target within the platelet–tumor axis.

Purpose To compare the DNA damage in granulosa cells (GCs) of women undergoing ovarian-stimulated cycles with four widely used recombinant human follicle-stimulating hormones (rhFSH) in in vitro fertilization (IVF) protocols (Corneumon^®, Gonal-F^®, Pergoveris^® and Puregon^®). Methods A randomized trial was carried out at a Mexican hospital. GCs were isolated from 18 women with infertility undergoing assisted reproductive techniques (ART). Four controlled ovarian stimulation (COS) protocols including Corneumon^®, Gonal-F^®, Pergoveris^® or Puregon^® were used. GCs DNA damage was assessed by the Comet assay. Two parameters were measured: comet tail length (CTL), and Olive tail moment (OTM, the percentage of DNA in the tail multiplied by the distance between the center of the tail and head). Results Use of the different hrFSH in COS caused variable and statistically significant levels of DNA damage in GCs of infertile women. CTL was similar in the Corneumon^® and Pergoveris^® groups (mean values of 48.73 and 55.18, respectively) and Corneumon^® CTL was significantly lower compared to the Gonal-F^® and Puregon^® groups (mean values of 61.98 and 91.17, respectively). Mean OTM values were significantly lower in Corneumon^® and Pergoveris^® groups, compared to Gonal-F^® and Puregon^® groups (25.59, 27.35, 34.76, and 47.27, respectively). Conclusion Use of Corneumon^® and Pergoveris^® in COS caused statistically significantly lower levels of DNA damage in GCs of infertile women undergoing ART, which could potentially correlate with better reproductive outcomes.

Cryptorchidism (CO) is a risk factor for the development of testicular germ-cell tumors (TGCT). This is supported by reports showing the persistence of gonocytes in CO patients. These cells are proposed to be related to the development of germ-cell neoplasia in situ (GCNIS), which is considered the precursor stage/lesion of TGCT. Therefore, it is proposed that some patients with CO could express some molecular markers related to TGCT. In this study, we analyzed testicular tissue samples from CO, TGCT, and controls. We determined the expression of POU5F1, PLAP, and KIT by immunohistochemistry and that of the hsa-miR-371-373 cluster, hsa-miR-367, and LATS2, PTEN, and IGFR1 genes by RT-qPCR. We then carried out a bioinformatic analysis to identify other possible candidate genes as tumor biomarkers. We found that 16.7% (2/12) of the CO patients presented increased expression of POU5F1, KIT, PLAP, hsa-miR-371-373, and hsa-miR-367 and decreased expression of LATS2 and IGF1R. Finally, the genes ARID4B, GALNT3, and KPNA6 were identified as other possible candidate tumor biomarkers. This is the first report describing the expression of the hsa-miR-371-373 cluster, hsa-miR-367, LATS2, and IGF1R in the testicular tissues of two CO patients with cells immune-positive to POU5F1, PLAP, and KIT, which is similar to what is observed in TGCT.

Some pediatric patients with cryptorchidism preserve cells with gonocyte characteristics beyond their differentiation period, which could support the theory of the gonocyte as a target for malignancy in the development of testicular neoplasia. One of the key molecules in gonocyte malignancy is represented by microRNAs (miRNAs). The goal of this review is to give an overview of miRNAs, a class of small non-coding RNAs that participate in the regulation of gene expression. We also aim to review the crucial role of several miRNAs that have been further described in the regulation of gonocyte differentiation to spermatogonia, which, when transformed, could give rise to germ cell neoplasia in situ, a precursor lesion to testicular germ cell tumors. Finally, the potential use of miRNAs as diagnostic and prognostic biomarkers in testicular neoplasia is addressed, due to their specificity and sensitivity compared to conventional markers, as well as their applications in therapeutics.

(1) Aim: In the present paper we analyzed the transcriptome of CSCs (Cancer Stem Cells), in order to find defining molecular processes of breast cancer. (2) Methods: We performed RNA-Seq from CSCs isolated from the basal cell line MDA-MB-468. Enriched processes and networks were studied using the IPA (Ingenuity Pathway Analysis) tool. Validation was performed with qRT-PCR and the analysis of relevant genes was evaluated by overexpression, flow cytometry and in vivo zebrafish studies. Finally, the clinical relevance of these results was assessed using reported cohorts. (3) Results: We found that CSCs presented marked differences from the non-CSCs, including enrichment in transduction cascades related to stemness, cellular growth, proliferation and apoptosis. Interestingly, CSCs overexpressed a module of co-regulated Chromosomal Passenger Proteins including BIRC5 (survivin), INCENP and AURKB. Overexpression of BIRC5 increased the number of CSCs, as assessed by in vitro and in vivo zebrafish xenotransplant analyses. Analysis of previously published cohorts showed that this co-regulated module was not only overexpressed in basal breast tumors but also associated with relapse-free and overall survival in these patients. (4) Conclusions: These results underline the importance of Cancer Stem Cells in breast cancer progression and point toward the possible use of chromosomal passenger proteins as prognostic factors.