Lipopolysaccharide Reduces the Primordial Follicle Pool in the Bovine Ovarian Cortex Ex Vivo and in the Murine Ovary In Vivo1

Abstract

Infections of the uterus or mammary gland with Gram-negative bacteria cause infertility in cattle, not only during disease but also for some time afterward. Even though these infections are in organs distant from the ovary, metritis and mastitis perturb antral follicle development and function in vivo. Although granulosa cells from antral follicles express toll-like receptor 4 (TLR4), and detect and mount an inflammatory response to lipopolysaccharide (LPS) from Gram-negative bacteria, it is not known whether LPS impacts preantral follicle development. The present study tested the hypothesis that LPS perturbs the development of primordial ovarian follicles. Exposure of bovine ovarian cortex ex vivo to LPS reduced the primordial follicle pool associated with increased primordial follicle activation. Ovarian cortex culture supernatants accumulated the inflammatory mediators IL-1beta, IL-6, and IL-8 in an LPS concentration-dependent manner. In addition, LPS exposure modulated key intracellular regulators of follicle activation with loss of the primordial follicle PTEN and cytoplasmic translocation of FOXO3. Acute exposure of mice in vivo to LPS also reduced the primordial follicle pool associated with increased follicle atresia. The increased follicle atresia was TLR4-dependent as Tlr4-deficient mice were insensitive to LPS-mediated follicle atresia. However, LPS did not affect the diameter of individually cultured bovine secondary follicles or their enclosed oocytes. In conclusion, LPS reduced the primordial ovarian follicle pool in the bovine ovarian cortex ex vivo and in the murine ovary in vivo. These observations provide an insight into how bacterial infections distant from the ovary have long term effects on fertility.

Comparing the effects of heat stress and mastitis on ovarian function in lactating cows: basic and applied aspects

“…However, the reason for this susceptibility is unclear. It is worth noting that other studies have shown functional impairment of small follicles and enclosed oocytes associated with exposure to various inflammatory agents [57,90,91].…”

Endotoxin exposure and puberty in female rats: the role of nitric oxide and caspase-1 inhibition in neonates

“…This suggests that for both the neonates and prepubescent rats, LPS was associated with a reduction in the number of primordial follicles. It was recently found that LPS reduces primordial follicle pool ex vivo in bovine ovarian cortex and in vivo in the murine ovary (Bromfield and Sheldon 2013). This reduction was associated with increased turnover of primordial follicles in bovine ovary, but it was associated with follicular atresia in mice (Bromfield and Sheldon 2013).…”

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

“…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).…”