Advanced maternal age is a risk factor for female infertility, and placental dysfunction is considered one of the causes of pregnancy complications. We investigated the effects of advanced maternal aging on pregnancy outcomes and placental senescence. Female pregnant mice were separated into three groups: young (2-3 months old), middle (8-9 months old), and aged (11-13 months old). Although the body weights of young and middle dams gradually increased during pregnancy, the body weight of aged dams only increased slightly. The placental weight and resorption rate were significantly higher, and live fetal weights were reduced in a maternal age-dependent manner. Although mRNA expression of senescence regulatory factors (p16 and p21) increased in the spleen of aged dams, mRNA expression of p16 did not change and that of p21 was reduced in the placenta of aged dams. Using a cytokine array of proteins extracted from placental tissues, the expression of various types of senescence-associated secretory phenotype (SASP) factors was decreased in aged dams compared with young and middle dams. The aged maternal placenta showed reduced immune cell accumulation compared with the young placenta. Our present results suggest that models using pregnant mice older than 8 months are more suitable for verifying older human pregnancies. These findings suggest that general cellular senescence programs may not be included in the placenta and that placental functions, including SASP production and immune cell accumulation, gradually decrease in a maternal age-dependent manner, resulting in a higher rate of pregnancy complications.

Problem Systemic inflammation induced by infection, which is associated with testicular inflammation, predisposes males to subfertility. Recently, the nucleotide‐binding oligomerization domain, leucine‐rich repeat‐, and pyrin domain‐containing 3 (NLRP3) inflammasome was identified as a key mediator of inflammation, and excessive activation of the NLRP3 inflammasome was shown to contribute to the pathogenesis of a wide variety of diseases. However, the mechanisms underlying infectious inflammation in the testis remain unclear. We investigated the effect of lipopolysaccharide (LPS)‐induced systemic inflammation on the role of the NLRP3 inflammasome in murine testes. Method of study We performed in vivo and in vitro studies using an LPS‐induced model of NLRP3 inflammasome activation and testicular inflammation. Results Intraperitoneal administration of LPS significantly impaired sperm motility in the epididymis of wild type (WT) and NLRP3‐knockout (KO) mice. LPS administration stimulated interleukin (IL)‐1β production and secretion in the testes of WT mice, and these adverse effects were improved in the testes of NLRP3‐KO mice. LPS administration also stimulated neutrophil infiltration as well as its chemoattractant C‐C motif chemokine ligand 2 (CCL2) in WT testes, which were suppressed in NLRP3‐KO testes. In in vitro cell culture, treatment with LPS and NLRP3 inflammasome activation significantly induced IL‐1β and CCL2 secretion from WT but not NLRP3‐KO testicular cells. Conclusions Taken together, our results suggest that testicular cells have the potential to secrete IL‐1β and CCL2 in an NLRP3 inflammasome‐dependent manner and that these cytokines from the testis may further exacerbate testicular function, resulting in subfertility during infectious diseases.

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