Influence of Lysophosphatidic Acid on Nitric Oxide-Induced Luteolysis in Steroidogenic Luteal Cells in Cows1

Abstract

Lysophosphatidic acid (LPA) together with its active G protein-coupled receptors are present in the corpus luteum (CL) of the cow. Under in vivo conditions, LPA stimulated P4 and PGE2 secretion during the luteal phase of the estrous cycle in heifers. Furthermore, LPA maintained P4 synthesis and actions in the bovine CL in vitro. However, the effect of this phospholipid on nitric oxide (NO)-induced functional and structural luteolysis has not been investigated. The aim of the present work was to determine the effects of LPA on 1) NO-induced functional luteolysis, 2) NO-dependent PG synthesis, and 3) NO-induced structural luteolysis in cultured steroidogenic luteal cells. We documented that LPA reversed the inhibitory effect of NONOate, an NO donor, on P4 synthesis and PGE2/PGF2alpha ratio in cultured steroidogenic luteal cells. Additionally, LPA inhibited NO-induced apoptosis in cultured steroidogenic luteal cells via abrogation of the NO-dependent stimulatory influence on proapoptotic TNFalpha/TNFR1 and Fas/FasL expression, Caspase 3 activity, and the Bax/Bcl2 ratio during luteal regression in the bovine CL. In conclusion, this study proves that in the presence of LPA, NO cannot induce luteolytic capacity acquisition, leading to functional and structural luteolysis of bovine luteal cells.

Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: AnIn VitroStudy

“…Also, GHR involvement in luteolysis is supported by the fact that TNF and nitrite secretions were also increased by this factor. As previously reported in equine [ 43 ] and bovine CL [ 50 ], nitrite and TNF were both shown to be involved in luteolysis, by directly increasing PGF 2 α or interacting with other cytokines, promoting structural luteolysis [ 4 ]. Thus, GHR may be integrated in the local auto- and paracrine set of interactions responsible for the amplification of luteolytic signal in equine CL.…”

Embryotrophic effect of a short-term embryo coculture with bovine luteal cells

“…Lysophosphatidic acid (LPA) is a well-known mediator of cell signaling in reproductive tissues [40]. Studies in cattle showed that luteal cells have receptors for LPA [41,42]. It was also observed that the in vitro supplementation of LPA after 48 h of IVC did not modify the percentages of bovine blastocysts.…”

Mechanisms of angioregression of the corpus luteum

“…L-arginine, an NOS substrate, increased apoptosis of cultured human luteal tissue, which was suppressed by treatment with an NO inhibitor (Vega et al, 2000). Similarly, treatment of bovine luteal cells with the NO donor, NONOate, increased levels of cleaved caspase 3, a marker of apoptosis (Korzekwa et al, 2006;Kowalczyk-Zieba et al, 2014). Conversely, treatment of luteinized goat granulosa cells with NO donor increased progesterone production, whereas treatment with an NOS inhibitor decreased progesterone and increased apoptosis (Guo et al, 2019).…”