Periovulatory Leukocyte Infiltration in the Rat Ovary

Abstract

Ovulation is preceded by intraovarian inflammatory reactions that occur in response to the preovulatory gonadotropin surge. As a main inflammatory event, leukocytes infiltrate the ovary and release proteolytic enzymes that degrade the extracellular matrix weakening the follicular wall, a required step for follicle rupture. This study aimed to quantitatively measure the infiltrating leukocytes, determine their cell types, and localize infiltration sites in the periovulatory rat ovary. Cycling adult and gonadotropin-stimulated immature rats were used as animal models. Ovaries were collected at five different stages of estrous cycle in the adult rats (diestrus, 1700 h; proestrus, 1500 h; proestrus, 2400 h; estrus, 0600 h; and metestrus, 1700 h) and at five different time points after superovulation induction in the immature rats (pregnant mare's serum gonadotrophin, 0 h; pregnant mare's serum gonadotrophin, 48 h; human chorionic gonadotropin, 6 h; human chorionic gonadotropin, 12 h; and human chorionic gonadotropin, 24 h). The ovaries were either dissociated into a single cell suspension for flow cytometric analysis or fixed for immunohistochemical localization of the leukocytes. Similar numbers of leukocytes were seen throughout the estrous cycle (approximately 500,000/ovary), except proestrus 2400 when 2-fold higher numbers of leukocytes were found (approximately 1.1 million/ovary). A similar trend of periovulatory rise of leukocyte numbers was seen in the superovulation-induced immature rat model, recapitulating a dramatic increase in leukocyte numbers upon gonadotropin stimulation. Both macrophage/granulocytes and lymphocytes were among the infiltrating leukocytes and were localized in the theca and interstitial tissues, where platelet-endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1 may play roles in the transmigration of leukocytes, because their expressions correlates spatiotemporally with the infiltrating leukocytes. In addition, a strong inverse relationship between leukocyte numbers in the ovary and spleen, as well as significant reduction of leukocyte infiltration in the splenectomized rats, were seen, indicating that the spleen may serve as an immediate supplier of leukocytes to the periovulatory ovary.

Involvement of Bone Marrow-Derived Vascular Progenitor Cells in Neovascularization During Formation of the Corpus Luteum in Mice1

“…Macrophages were present in the theca cell layer before hCG injection and increased in number during CL formation after ovulatory hCG stimulation, in good agreement with previous reports [15,32]. Our result also shows that many of the bone marrow-derived cells recruited to the CL during CL formation were macrophages.…”

“…Furthermore, macrophage ablation was recently been shown to disrupt ovarian vascular integrity in mice, suggesting that macrophages play a functional role in supporting CL vasculature [14]. Interestingly, the number of macrophages was found to increase in follicles undergoing luteinization after the ovulatory LH surge [15]. Therefore, it is likely that macrophages also play a role in the neovascularization that occurs during CL formation.…”

Why two endothelins and two receptors for ovulation and luteal regulation?

“…However, this concept has been challenged because the presumed pressure increase at the time of follicle rupture has never been documented (Espey and Lipner, 1963;Rondell, 1964). Instead, more attention has focused on the view that ovulation results from the proteolytic degradation of the follicular wall, which is supported by the functional presence of matrix metalloproteinases/plasminogen activators and inflammatory leukocytes in the ovary (Brannstrom and Enskog, 2002;Curry and Osteen, 2003;Oakley et al, 2010Oakley et al, , 2011Richards et al, 2002).…”

Estrogen Receptors in Leukocytes - Possible Impact on Inflammatory Processes in the Female Reproductive System

“…Infiltration of leukocytes into the ovary is essential for ovulation. The invading leukocytes secrete proteases to weaken the follicular wall and thus aiding ovulation (Oakley et al, 2010). These leukocytes include macrophages and lymphocytes (Oakley et al, 2010).…”

“…The invading leukocytes secrete proteases to weaken the follicular wall and thus aiding ovulation (Oakley et al, 2010). These leukocytes include macrophages and lymphocytes (Oakley et al, 2010). Leukocytes are present in great numbers and diversity in the reproductive tract throughout the reproductive cycle.…”