In vivo effect of vaginal seminal plasma application on the human endometrial transcriptome: a randomized controlled trial.

Studies in humans and animals suggest that seminal plasma, the acellular seminal fluid component, stimulates the endometrium to promote immune tolerance and facilitate implantation. We designed a randomized, double-blinded, placebo-controlled trial to investigate changes in the endometrial transcriptomic profile after vaginal application of seminal plasma. The study participants were randomized into two groups. Five women received a vaginal application of seminal plasma, and four received a placebo application with saline solution. The application was performed 2 days after HCG-triggered ovulation in an unstimulated cycle. After 5-8 days, an endometrial biopsy was collected to analyze differences in the endometrial transcriptomic profile using microarray analyses. A differential gene expression analysis and a gene set analysis were performed. The gene set enrichment analysis showed a positive enrichment of pathways associated with the immune response, cell viability, proliferation, and cellular movement. Moreover, pathways involved in implantation, embryo development, oocyte maturation, and angiogenesis were positively enriched. The differential gene expression analysis, after adjusting for multiple testing, showed no significantly differentially expressed genes between the two groups. A comparative analysis was also performed with similar studies conducted in other animals or in vitro using human endometrial cells. The comparative analysis showed that the effect of seminal plasma effect on the endometrium is similar in pigs, mice, and in vitro human endometrial cells. The present study provides evidence that seminal plasma might impact the endometrium during the implantation window, with potential to affect endometrial receptivity and embryo development.

Empowering tomorrow's leaders: the impact of the 15th Network of Young Researchers in Andrology (NYRA) meeting on male reproductive health and interdisciplinary collaboration.

The 15th Network of Young Researchers in Andrology (NYRA) meeting, held at the Palace de Caux, Switzerland, served as a valuable platform to disseminate cutting-edge research and facilitate interactions among early-career researchers and trainees in andrology from around the world. Preceding the 22nd European Testis Workshop, the 2-day event brought together participants from a variety of countries to discuss a range of topics pertaining to men's reproductive health and biology. Specific focuses included piRNAs in mammalian reproduction, biomolecules enhancing sperm physiology, advances in in vitro spermatogenesis, reproductive strategies across species, and career development. A dedicated 'scientific speed-dating' social event also stood out, encouraging cross-disciplinary collaborations and strengthening ties within the scientific community. The high participation rate of the meeting highlighted its value in connecting the andrology community. Finally, the announcement of NYRA's merger with the European Academy of Andrology (EAA) marked a pivotal moment, enabling NYRA to support young researchers while collaborating with the EAA to advance andrology research. The 15th NYRA meeting played a crucial role in enhancing knowledge dissemination and andrology research, empowering young researchers, and addressing key challenges in male infertility.

Direct action of endocrine disrupting chemicals on human sperm.

Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm-specific CatSper channel and, thereby, evoke an intracellular Ca(2+) increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low-dose mixtures to elevate Ca(2+) levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization.

Primary cilia and aberrant cell signaling in epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the fourth leading cause of cancer-related deaths among women in Denmark, largely due to the advanced stage at diagnosis in most patients. Approximately 90% of ovarian cancers originate from the single-layered ovarian surface epithelium (OSE). Defects in the primary cilium, a solitary sensory organelle in most cells types including OSE, were recently implicated in tumorigenesis, mainly due to deregulation of ciliary signaling pathways such as Hedgehog (Hh) signaling. However, a possible link between primary cilia and epithelial ovarian cancer has not previously been investigated. METHODS: The presence of primary cilia was analyzed in sections of fixed human ovarian tissue as well as in cultures of normal human ovarian surface epithelium (OSE) cells and two human OSE-derived cancer cell lines. We also used immunofluorescence microscopy, western blotting, RT-PCR and siRNA to investigate ciliary signaling pathways in these cells. RESULTS: We show that ovarian cancer cells display significantly reduced numbers of primary cilia. The reduction in ciliation frequency in these cells was not due to a failure to enter growth arrest, and correlated with persistent centrosomal localization of aurora A kinase (AURA). Further, we demonstrate that ovarian cancer cells have deregulated Hh signaling and platelet-derived growth factor receptor alpha (PDGFRα) expression and that promotion of ciliary formation/stability by AURA siRNA depletion decreases Hh signaling in ovarian cancer cells. Lastly, we show that the tumor suppressor protein and negative regulator of AURA, checkpoint with forkhead-associated and ring finger domains (CHFR), localizes to the centrosome/primary cilium axis. CONCLUSIONS: Our results suggest that primary cilia play a role in maintaining OSE homeostasis and that the low frequency of primary cilia in cancer OSE cells may result in part from over-expression of AURA, leading to aberrant Hh signaling and ovarian tumorigenesis.