Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause

Abstract

The purpose of this investigation was to localize and characterize white blood cell populations in the human ovary through its physiological life cycle. Ovaries from 30 women of reproductive age and from three post-menopausal women were embedded in paraffin or frozen. Clinical information and pathology review were used to obtain accurate menstrual cycle information and to ensure the absence of ovarian disease. Tissue sections were stained for leukocyte phenotypes and the numbers of white blood cells in the ovary were semiquantitatively assessed by two separate examiners using a 0-3 plus (+) scoring system. Our results demonstrated that macrophages and T lymphocytes were the primary immune cells of the ovary, the concentrations of which were dependent on the location and stage of development of the structures containing leukocytes. Developing follicles contained few (+) macrophages located in the theca, while atretic follicles possessed moderate (+2) numbers in the granulosa and few (+) to moderate (+2) numbers in the theca. Newly formed corpora lutea contained few (+) macrophages, while regressing corpora lutea contained abundant (+3) numbers. Human leukocyte antigen (HLA)-DR positive cells were located predominantly at sites where macrophages were present. T lymphocytes were generally not present in the developing follicle but focal, small (+) numbers were observed in blood vessels of the theca. Atretic follicles contained few (+) T lymphocytes in the granulosa and few (+) to moderate (+2) numbers in the theca. Few (+) T lymphocytes were present in new corpora lutea, while moderate (+2) to abundant (+3) numbers were present in regressing corpora lutea. T lymphocytes at all sites were UCHL1 positive. The CD4 (T helper) to CD8 (T suppressor) ration in the corpus luteum was 1:1. B-lymphocytes and natural killer cells were generally absent in the pre-menopausal ovary. The post-menopausal ovary, in contrast, only contained few (+) macrophages, T lymphocytes and natural killer cells in the stroma. In conclusion, our results indicate that the human ovary is an immunologically dynamic tissue containing activated macrophages and T lymphocytes which provide an anatomical basis for immunoendocrine interactions within the ovary.

In vitro evidence that hyperglycemia stimulates tumor necrosis factor-α release in obese women with polycystic ovary syndrome

“…We have also demonstrated direct correlations of ROS generation (González et al 2006) and activated NF B (unpublished data) with these androgen levels. Infiltration of the ovary by MNC-derived macrophages has been previously reported (Best et al 1996). Ovarian steroidogenic enzymes responsible for androgen production are stimulated by oxidative stress and inhibited by antioxidants, such as statins, in vitro .…”

HLA‐class II haplotype associations with ovarian cancer

“…19 Because the latter interact with HLA molecules, it must be concluded that the MHC complex plays a central role within the immunological integrity of the ovary. Evidence from a number of studies supports the notion that in several tumor systems tumor-infiltrating lymphocytes may represent an active immune response of the host directed against the tumor.…”

Ovulation as danger signaling event of innate immunity

“…In the preovulatory follicle wall, mast cells appear to be absent and the number of T cells as main representatives of the adaptive immune system are low in number (Best et al, 1996;Spanel-Borowski et al, 1997;Bauer et al, 2001). It points to a minor cross-talk between INIM and adaptive immunity.…”

“…Page 11 with the adaptive immunity, whereas augmented T cells in the CL of regression speaks for exchanges between the two immune systems (Best et al, 1996;Spanel-Borowski et al, 1997;Bauer et al, 2001). A disturbed conversation between INIM and adaptive immunity is reflected by altered T cell profiles in the follicular fluid of patients with idiopathic infertility and in ovaries with premature ovarian failure due to autoimmune damage (Lukassen et al, 2003;Vujovic, 2009 (Banchereau and Steinman, 1998;Mellman and Steinman, 2001;Turvey and Broide, 2010), DCs are key players between INIM and adaptive immunity.…”