Tatsuya Kobayashi

This retrospective study evaluated whether sperm DNA fragmentation (SDF), measured by DNA fragmentation index (DFI), predicts IVF outcomes in 124 couples undergoing IVF with PGT-A (Preimplantation Genetic Testing for Aneuploidy) between 2015 and 2023. SDF was assessed using the Halosperm kit and categorized into low (≤ 15%, n = 81), medium (15-30%, n = 34), and high (≥ 30%, n = 9) DFI groups. Fertilization was performed via IVF or ICSI, and embryos were analyzed with PGT-A using next-generation sequencing. High DFI was associated with advanced paternal age, reduced motility, lower fertilization rates (in ICSI), and fewer good-quality blastocysts. However, PGT-A outcomes showed no significant differences in euploidy, mosaicism, or aneuploidy rates across DFI groups. Similarly, despite the methodological limitations of a retrospective design and a highly selected cohort, implantation, pregnancy, and live birth rates following euploid embryo transfer were unaffected by DFI level. SDF testing can help identify male infertility factors and guide IVF strategy, particularly regarding sperm selection. These findings suggest that early developmental impairment from sperm DNA damage may possibly be mitigated by embryonic repair mechanisms at later stages.

Estrogen is synthesized throughout various tissues in the body, and its production is regulated by the rate-limiting enzyme aromatase (encoded by the Cyp19a1 gene). Notably, aromatase is also expressed in central nervous system cells, allowing for localized estrogen synthesis in regions such as the hypothalamus. Estrogens produced within these neurons are referred to as neuroestrogens. In this study, we investigated the role of neuroestrogens in the regulation of appetite through modulation of hypothalamic pathways in OVX, ArKO, and aromatase-restored mice. Estrogen suppresses appetite by influencing the expression of appetite-regulating peptides, including POMC and NPY, via MC4R. We explored the direct effects of neuroestrogens, independent from ovarian estrogen, on appetite suppression and the underlying molecular mechanisms. We monitored body weight and food intake and evaluated the expression of Cyp19a1, Mc4r, and other appetite-related genes. Our findings indicate that OVX and ArKO mice exhibited increased body weight and food consumption, which correlated with altered expression of Mc4r and Cyp19a1. Conversely, restoration of Cyp19a1 expression in a neuron specific manner significantly decreased food intake and increased Mc4r expression in the hypothalamus. Furthermore, neuroestrogens enhanced leptin responsiveness. Our results imply that neuroestrogens likely contribute to appetite regulation and may be relevant for body weight reduction.