Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis

Abstract

Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E 2 (PGE 2 ) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE 2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-a production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary.Reproduction (2015) 150 437-448

Polycystic ovary syndrome: possible involvement of androgen-induced, chemerin-mediated ovarian recruitment of monocytes/macrophages†

“…These responses appeared to be follicle stage-specific and critical for normal follicle growth. DHT treatment disrupted the M1: M2 ratio and therefore the inflammatory versus anti-inflammatory signaling in the ovaries [34,35] and potentially contributing to the apoptosis in granulosa cells [36,37].…”

Sympathetic innervation regulates macrophage activity in rats with polycystic ovary

“…2. In a previous study, we observed that MФ from PCO rats released more NO than Control MФ (Figueroa et al 2015). In this case, the SON section caused a decrease in the release of nitrites from PCO-SON MФ in relation to PCO MФ (P < 0.05).…”

“…The measurement of serum A2 levels showed a decrease in PCO-SON rats compare to PCO rats, reaching a similar value to control rats (PCO: 1.88 ± 0.10; PCO-SON: 1.50 ± 0.12; C: 1.45 ± 0.07; ng/mL; PCO vs PCO-SON and C rats, P < 0.05). This, along with our previous results showing that the androgen microenvironment induces the production of TNFα by PCO MФ (Figueroa et al 2015), led us to determine whether the SON section affects TNFα release and its mRNA expression in PCO MФ. As shown in Fig.…”

“…After incubation for 2 h at 37°C in 95% air-5% CO 2 , non-adherent cells were removed. The adherent MΦ monolayer showed 90% of purity according to the morphologic analysis performed by Giemsa staining and nonspecific esterase staining (Figueroa et al 2015). MΦ from PCO rats (PCO MΦ), from PCO rats with bilateral SON section (PCO-SON MΦ) and from Control rats (Control MΦ) were plated at a density of 1 × 10 6 cells/well, preincubated in 1 mL of BM for 24 h and subsequently cultured for 24 h. The respective culture media (also called MΦ secretions) were collected and used to stimulate ovaries from PCO (PCO ovaries) and PCO-SON rats (PCO-SON ovaries).…”

The role of macrophages in reproductive-related diseases

“…Cytokines secreted by splenic macrophages from PCOS mouse stimulated androstenedione production by granulosa cells and inhibited estradiol production, but the exact cytokines are unknown [ 66 ]. Excessive androgen inhibited the macrophage viability and increased macrophage apoptosis [ 67 ], and promoted pro-inflammatory cytokines expression, such as TNF-α [ 68 ]. The increased TNF-α in turn inhibited estradiol production [ 68 ].…”