Some aspects of regulation of luteal function and luteolysis in equine corpora lutea

Abstract

SummaryLike in other mammalian species, in the mare, in every ovarian cycle, a complex process of luteinization leads to corpus luteum (CL) formation. The CL produces progesterone (P4), a required hormone for establishment and maintenance of early pregnancy. Luteal angiogenesis in the mare, necessary for the CL formation, is followed by vascular regression during tissue involution, coordinated with the development and regression of non-vascular tissue (steroidogenic cells included). These processes might be regulated by several factors, still not completely understood. This work reviews some of our studies on this field in the mare. In the equine CL, tumour necrosis factor (TNFα) and nitric oxide (NO) may stimulate the production of angiogenic factor(s) and prostaglandin (PG) E2, necessary for vascular and non-vascular development during the early luteal phase. Increased microvascularization is accompanied by the synthesis of P4, rise in P4 receptor number and an increase in the number of large luteal cells. This suggests the importance of large luteal cells in the auto/paracrine regulation of P4 synthesis in the equine CL. However, when angiogenesis is complete, long term exposure to progestagens appears to inhibit the proliferative/angiogenic activity. PGF2α may also induce luteal (including vascular) regression of the equine CL. Moreover, NO and P4 dependent process of inhibition of angiogenic factor(s) production might be preparing the CL for functional and structural regression. Oppositely to the early luteal phase, during late luteal phase NO and cytokines may induce several processes leading to the regression of equine CL. Besides, caspase-3, the effector enzyme of apoptosis, might also play an important role during luteal tissue involution. Nevertheless, further studies are needed to elucidate the mechanisms and the relationship between the dichotomy of loss of function and/or luteal involution in the mare.

Regulation of Luteal Function and Corpus Luteum Regression in Cows: Hormonal Control, Immune Mechanisms and Intercellular Communication

“…1) (Reynolds and Redmer 1999; Acosta and Miyamoto 2004; Schams and Berisha 2004; Meidan et al. 2005; Ferreira‐Dias and Skarzynski 2008). After ovulation, as the CL forms from the wall of the ruptured follicle, it grows and vascularizes rapidly.…”

“…In agreement with data from other tissues, VEGF seem to be a major angiogenic factor responsible for vascularization of the developing CL. Recent data suggest that luteal expression of VEGF occurs primarily in steroidogenic cells (granulose‐lutein cells) and less in endothelial cells (specific perivascular cells, including arteriolar smooth muscle and capillary pericytes), and is regulated primarily by oxygen levels (Berisha and Schams 2005; Ferreira‐Dias and Skarzynski 2008). Soon after ovulation, pericytes derived from the thecal compartment appear to be the first vascular cells to invade the developing luteal parenchyma.…”

“… Hypothetical model of the structural and functional regression of the CL (see text for the details; adapted from Ferreira‐Dias and Skarzynski 2008) …”

Endothelial cells and angiogenesis in the horse in health and disease—A review

“…On day 3 before ovulation, NO peaked and thereafter decreased until ovulation (Abdelnaby & El‐Maaty, 2017). The effect of TNF and NO on the production of angiogenic factors and prostaglandin E2 was studied in cultured equine explants of corpora lutea (Ferreira‐Dias & Skarzynski, 2008). The secretory function and the release of angiogenic factors of equine corpora haemorrhagica were found to be stimulated by TNF and NO (Ferreira‐Dias et al., 2011).…”

“…The secretory function and the release of angiogenic factors of equine corpora haemorrhagica were found to be stimulated by TNF and NO (Ferreira‐Dias et al., 2011). During the late luteal phase, NO and progesterone 4 inhibit angiogenesis, preparing the CL for functional and structural regression (Ferreira‐Dias & Skarzynski, 2008). Leptin and ghrelin play opposing roles during development and regression of the equine CL, with leptin promoting angiogenesis and ghrelin enhancing luteolysis (Galvao et al., 2014).…”