Role of Inflammaging on the Reproductive Function and Pregnancy

Abstract

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health.

Keywords: Aging; Fertility; Fetal programming; Inflammaging; Maternal low-grade chronic inflammation; Senescence.

Fig. 1

Inflammaging effects on pregnancy, mother and offspring: On the left etiological factors contributing to the pathogenesis of inflammaging; on the right effects of inflammaging on pregnancy, maternal, and offspring outcomes and potential feedback loop of pregnancy effects on inflammaging and chronic age-related diseases onset; FGR fetal growth restriction, GDM gestational diabetes mellitus

Fig. 2

Inflammaging as a synergic result of the interaction among many co-factors

Fig. 3

Effects of Inflammaging on fertility. Fertility spontaneously declines as women age. However, higher levels of inflammation lead to a faster reduction of the ovarian reserve, as well as are associated with poor quality embryos and inadequate endometrial receptivity in In-Vitro Fertilization (IVF) treatments. Reduction of risk factors has a positive impact on inflammation and, in turn, on female fertility

Fig. 4

Inflammaging and pregnancy effect on aging trajectories and age-related diseases outbreak. Solid lines (red, blue and green) represent the trajectories of aging of three women, diverging from the beginning as an effect of different intra-uterine environment and experiences in early life. Line slopes are affected by the occurrence of inflammaging acting as an accelerator toward the onset of age-related diseases. Dashed lines show the effect of pregnancy on the progression of aging trajectories, playing the role of a second hit accelerator to the pathological inflammatory threshold and disease outbreaks