The effect of leptin on luteal angiogenic factors during the luteal phase of the estrous cycle in goats

Abstract

Fibroblast growth factor 2 (FGF2), angiopoietin 1 (Ang1), and vascular endothelial growth factor (VEGF) are angiogenic factors implicated in the vascular development of the corpus luteum (CL). Each factor is regulated or influenced by leptin in non-ovarian tissues. Moreover, leptin and its receptor, ObRb, have been identified in luteal tissue throughout the luteal phase. Therefore, leptin is hypothesized to influence luteal vasculature through the regulation of FGF2, Ang1, and VEGF. Multiparous, cycling crossbred female goats (does) were allocated to early (n=12), mid (n=8), and late (n=11) stages of the luteal phase for CL collection. Luteal tissue was harvested and either snap frozen in liquid N2, paraffin embedded, or cultured with leptin (0, 10−12, 10−11, 10−10, 10−9, 10−8 M). Tissue was analyzed for FGF2, Ang1, VEGF, ObRb, and leptin expression. Angiopoietin 1, FGF2, VEGF expression was higher (P≤0.001) in the mid-luteal stage than the early stage. Expression decreased (P≤0.001) during the late luteal stage with the exception of VEGF, which remained elevated. In contrast, leptin and ObRb were lowest (P≤0.003) during the mid-luteal stage compared to the early and late stages. All factors were detected in and/or around vessels in early stage tissue compared to mid and late stages. Leptin stimulated (P≤0.02) Ang1, FGF2, and VEGF expression only in early stage luteal cultures. Collectively, these data provide evidence that leptin may be involved in the luteal angiogenic process during the early stage of CL formation.

Expression and localization of angiopoietin family in corpus luteum during different stages of oestrous cycle and modulatory role of angiopoietins on steroidogenesis, angiogenesis and survivability of cultured buffalo luteal cells

“…VEGF and ANGPT 2:1 ratio plays a significant role in angiogenesis and regression of blood vessels (Schams & Berisha, ; Shimizu, Berisha, Schams, & Miyamoto, ). Angiopoietins are responsible for steroidogenesis and luteal function in cattle (Tanaka et al., ; Wiles et al., ). The mRNA of ANGPT‐Tie system was expressed in CL of cattle (Hayashi et al., ; Sugino et al., ).…”

Luteal blood flow and growth in correlation to circulating angiogenic hormones after spontaneous ovulation in mares

“…Ovaries are able to produce small amounts of leptin which modulate their function during different reproductive conditions (Fruhbeck, 2006). Both circulating and locally produced leptin may be involved in the luteal angiogenic process through regulation of potent angiogenic hormones and both leptin and its receptors had been identified in luteal tissue and were hypothesised to influence luteal vasculature through the regulation of PGF 2α (Wiles et al, 2014). The high serum leptin levels during early luteal growth compared to mid-luteal static phase of mares could be attributed to the decreased expression of leptin receptors during the mid-luteal stage compared to the early stage (Wiles et al, 2014).…”

“…Both circulating and locally produced leptin may be involved in the luteal angiogenic process through regulation of potent angiogenic hormones and both leptin and its receptors had been identified in luteal tissue and were hypothesised to influence luteal vasculature through the regulation of PGF 2α (Wiles et al, 2014). The high serum leptin levels during early luteal growth compared to mid-luteal static phase of mares could be attributed to the decreased expression of leptin receptors during the mid-luteal stage compared to the early stage (Wiles et al, 2014). Also, the relaxing effect of leptin on blood vessels was partially mediated by the NO-dependent pathway and phenylephrine-contracted arterial rings were relaxed by leptin that mediated through endothelial NO production (Kimura et al, 2002).…”

Inflammation and angiogenesis in the corpus luteum

“…Furthermore, there are also some distinct differences between the CL of primates and ruminants, such as the P4 production, pregnancy maintenance and CL regression . However, inadequate functioning of the CL leads to infertility and increases in pregnancy failure in mice, goats and nonhuman primates . Therefore, the CL exerts important effects on female reproduction and embryonic growth.…”

“…15 However, inadequate functioning of the CL leads to infertility and increases in pregnancy failure in mice, goats and nonhuman primates. 10,16,17 Therefore, the CL exerts important effects on female reproduction and embryonic growth.…”