Ovarian follicular cells have innate immune capabilities that modulate their endocrine function

Abstract

Oestrogens are pivotal in ovarian follicular growth, development and function, with fundamental roles in steroidogenesis, nurturing the oocyte and ovulation. Infections with bacteria such as Escherichia coli cause infertility in mammals at least in part by perturbing ovarian follicle function, characterised by suppression of oestradiol production. Ovarian follicle granulosa cells produce oestradiol by aromatisation of androstenedione from the theca cells, under the regulation of gonadotrophins such as FSH. Many of the effects of E. coli are mediated by its surface molecule lipopolysaccharide (LPS) binding to the Toll-like receptor-4 (TLR4), CD14, MD-2 receptor complex on immune cells, but immune cells are not present inside ovarian follicles. The present study tested the hypothesis that granulosa cells express the TLR4 complex and LPS directly perturbs their secretion of oestradiol. Granulosa cells from recruited or dominant follicles are exposed to LPS in vivo and when they were cultured in the absence of immune cell contamination in vitro they produced less oestradiol when challenged with LPS, although theca cell androstenedione production was unchanged. The suppression of oestradiol production by LPS was associated with down-regulation of transcripts for aromatase in granulosa cells, and did not affect cell survival. Furthermore, these cells expressed TLR4, CD14 and MD-2 transcripts throughout the key stages of follicle growth and development. It appears that granulosa cells have an immune capability to detect bacterial infection, which perturbs follicle steroidogenesis, and this is a likely mechanism by which ovarian follicle growth and function is perturbed during bacterial infection.

Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows

“…In addition to being detected in the uterus and peripheral circulation, LPS has been detected in follicular fluid of cattle with uterine disease; unsurprisingly, concentrations of LPS are directly correlated with bacterial load. Mateus et al, 2003;Herath et al, 2007;. Administration of intravenous LPS disrupts neuroendocrine activity and results in interference with the oestrous cycle.…”

“…These studies provide evidence for localized effects of LPS in the ovary. Indeed, in vitro LPS has been shown to disrupt granulosa cell oestradiol secretion via reduced expression of aromatase enzyme expression (Herath et al, 2007) and acute exposure to LPS increases follicular atresia and reduces the primordial ovarian follicle pool (Bromfield and Sheldon, 2013).…”

The effects of periparturient events, mastitis, lameness and ketosis on reproductive performance of Holstein cows in a hot environment

“…A variety of bioactive molecules (e.g. TNF-α, NO, and PGF2-α, among many others) from the infected mammary gland are released into the bloodstream which have the capacity to disrupt tissues involved in reproduction, such as the ovary (Herath et al 2007), hypothalamus (Schrick et al 2001, Nugent et al 2002, and endometrium (Herath et al 2009). Additionally, follicle growth (Herath et al 2007), and oocyte and embryonic development (Soto et al 2003) are also hampered by endotoxins.…”

“…TNF-α, NO, and PGF2-α, among many others) from the infected mammary gland are released into the bloodstream which have the capacity to disrupt tissues involved in reproduction, such as the ovary (Herath et al 2007), hypothalamus (Schrick et al 2001, Nugent et al 2002, and endometrium (Herath et al 2009). Additionally, follicle growth (Herath et al 2007), and oocyte and embryonic development (Soto et al 2003) are also hampered by endotoxins. Finally, it should be noted that heat stress (Roth and Wolfenson 2016) and subclinical ketosis (Albaaj et al 2017) seem to have an additive deleterious effect together with CM on fertility of dairy cows.…”

Effect of Escherichia coli infection of the bovine uterus from the whole animal to the cell

“…More recently, we have shown that animals with high numbers of the recognised uterine pathogens including E. coli have retarded ovarian follicle growth, lower peripheral plasma concentrations of oestradiol and an inability to form a competent corpus luteum (CL) ( Table 1; Williams et al, 2007). Lipopolysaccharide (LPS), the main pathogenic moiety of E. coli, is detectable in the uterus, peripheral plasma and ovarian follicular fluid of cows with post partum uterine infection (Peter et al, 1989;Mateus et al, 2003;Herath et al, 2007;Williams et al, 2007). Administration of intravenous LPS disrupts neuroendocrine activity and results in interference with the oestrous cycle.…”