Age-dependent changes in inflammation and extracellular matrix in bovine oviduct epithelial cells during the post-ovulatory phase

Abstract

The mammalian oviduct is an essential site for sperm storage, the transport of gametes, fertilization, and embryo development-functions that are aided by cytokines secreted from oviduct epithelial cells (OECs). Aging leads to cellular and organ dysfunction, with infertility associated with advanced maternal age. Few studies have investigated age-dependent changes in the oviduct as a possible cause of infertility, so we compared OECs from young (30-50 months) versus aged (more than 120 months) cattle. Next-generation sequencing was first used to identify age-related differences in gene expression. Several proinflammatory-related genes (including IL1B, IL1A, IL17C, IL8, S100A8, S100A9, and TNFA) were activated in OECs from aged (more than 120 months) compare to young (30-50 months) individuals, whereas genes associated with extracellular matrix-related factors (COLs, POSTN, BGN, and LUM) were down-regulation in aged OECs. Indeed, IL1 B and IL8 abundance was higher in aged OECs than in young OECs. Young OECs also tended to proliferate faster, and the revolution frequency of young, ciliated OECs was higher than that of their aged counterparts. In contrast, aged OECs possessed more F-actin, an actin cytoskeleton marker associated with reduced elasticity, and contained high levels of reactive oxygen species, which are mediators of inflammation and senescence. These different functional characteristics of bovine OECs during the post-ovulatory phase support the emerging concept of "inflammaging," that is, age-dependent inflammation. Mol. Reprod. Dev. 83: 815-826, 2016 © 2016 Wiley Periodicals, Inc.

Age‐related changes in the bovine corpus luteum function and progesterone secretion

“…The concept of "inflammageing" has recently emerged, which describes an age-dependent, low-grade, chronic and systemic inflammatory state induced by SASP, which is produced by the innate immune, parenchymal and nonparenchymal cells within the organs (Goto, 2008). These SASPs investigated in this study have potential role to regulate luteal function such as P4 secretion (Hashii et al, 1998;Jiemtaweeboon et al, 2011;Kohen et al, 1999 Recently, we reported that maternal age affects the upregulation of genes related to immune and inflammatory responses in bovine oviduct epithelial and endometrial cells, which suggested the occurrence of "inflammageing" in the bovine oviduct and uterus (Tanaka et al, 2016;Tanikawa et al, 2017). However, in the present study, no increase in the expression of SASP-related cytokine genes was observed in the CL tissue from aged cows in comparison with young animals.…”

“…These SASPs investigated in this study have potential role to regulate luteal function such as P4 secretion (Hashii et al, ; Jiemtaweeboon et al, ; Kohen et al, ; Sakumoto, Komatsu, Kasuya, Saito, & Okuda, ; Shimizu et al, ). Recently, we reported that maternal age affects the upregulation of genes related to immune and inflammatory responses in bovine oviduct epithelial and endometrial cells, which suggested the occurrence of “inflammageing” in the bovine oviduct and uterus (Tanaka et al, ; Tanikawa et al, ). However, in the present study, no increase in the expression of SASP‐related cytokine genes was observed in the CL tissue from aged cows in comparison with young animals.…”

Adverse reproductive effects of S100A9 on bovine sperm and early embryonic development in vitro

“…The fertilization rate of cattle is as high as 90% when appropriate artificial insemination is used, but the pregnancy success rate is below 50%, indicating that the rate of early embryo loss in cows is very high [2]. It has been suggested that the oviduct is crucial for creating an appropriate microenvironment for fertilization and early embryogenesis; therefore, dysfunction in the oviduct may lead directly to infertility [3].…”

“…With aging, oocytes exhibit abnormal chromosome division, decreased mitochondrial quality, including the accumulation of mutations in the mitochondrial DNA and low ATP production, increased oxidative stress, and decreased levels of antioxidants [5][6][7]. We previously demonstrated that the functional characteristics of the bovine oviduct and uterus change with agedependent upregulation of inflammation [3,8]. We also reported that aged bovine oviduct epithelial cells expresses inflammation-related factors at high levels, especially S100A9, and S100A9 triggers of inflammatory responses in oviduct epithelial cells [9].…”

Age-associated mRNA expression changes in bovine endometrial cells in vitro

“…In terms of reproduction, it is well known that advanced maternal age is associated with reduced fertility and adverse pregnancy outcomes, and the age-related decline in oocyte quality is well understood [ 13 , 14 ]. We recently suggested that the oviduct senescence was dependent on the aging of cows because aged oviduct epithelial cells exhibited higher levels of inflammatory cytokines, excessive reactive oxygen species production, and decreased villous and proliferative activities compared to young oviduct epithelial cells in cattle [ 15 ]. In terms of uterine function, the uterine dysfunction and senescence and contractile activity in the myometrium in young rats was significantly greater than that in aged rats [ 16 ].…”