Abstract
Advanced maternal age is associated with adverse pregnancy outcomes and the decline of female fertility in mammals. A potential reason for reduced fertility is metabolic changes due to protein modifications by advanced glycation end products. To elucidate the aging process in female reproduction, we analysed a key enzyme for detoxification of reactive dicarbonyls, the glyoxalase 1 (GLO1), in reproductive organs and blastocysts of young and old rabbits at the preimplantation stage. At day 6 post coitum, uterine, oviductal, ovarian tissue and blastocysts from young (16–20 weeks) and old rabbits (>108 weeks) were characterised for GLO1 expression. GLO1 amounts, enzymatic activity and localisation were quantified by qPCR, Simple Western, activity assay and immunohistochemistry. The GLO1 enzyme was present and active in all reproductive tract organs in a cell-type-specific pattern. Ovarian follicle and uterine epithelial cells expressed GLO1 to a high extent. In tertiary follicles, GLO1 expression increased, whereas it decreased in the endometrium of old rabbits at day 6 of pregnancy. In blastocysts of old animals, GLO1 expression remained unchanged. In early pregnancy, advanced maternal age leads to modified GLO1 expression in ovarian follicles and the endometrium, indicating an altered metabolic stress response at the preimplantation stage in older females.
Highlights
Over the past three decades there has been a pronounced increase in the number of births by older women, especially in their late 30s and 40s, in many high-income countries [1,2,3]
We have recently shown that advanced glycation end products (AGEs) are present in ovarian tissues and embryos in rabbits [28]
We investigated the impact of maternal age on glyoxalase 1 (GLO1) expression and localisation in female reproductive organs and embryos at the preimplantation stage
Summary
Over the past three decades there has been a pronounced increase in the number of births by older women, especially in their late 30s and 40s, in many high-income countries [1,2,3]. The mean age of women at birth of their first child has gradually increased from 27.0 in 1987 to 29.3 in 2018 in the European Union [4]. It is well known that the developmental potential of oocytes declines with increasing age, referred to as ovarian aging. This phenomenon is characteristic for humans, but for all mammals [5,6,7]. It has been proposed that during the reproductive lifespan, ovarian follicles and reproductive tissues become exposed to factors that accumulate irreversibly, leading to an age-related decline of fertility [12,13]
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