Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition

Abstract

BackgroundEndocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr), the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog.MethodsThe expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o.) as well as in CL, the utero/placental compartments (Ut/Pl) and interplacental free polar zones (interplacental sites) from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization.ResultsIn non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated.ConclusionsThe data presented suggest that the luteal provision of P4 in both pregnant and non-pregnant dogs may be regulated at the PRLr level. Furthermore, a role of PRL not only in maintaining the canine CL function but also in regulating the placental function is strongly suggested. A possible functional interrelationship between luteal P4 and placental and luteal PRLr expression also with respect to the prepartal luteolysis is implied.

Formation of the early canine CL and the role of prostaglandin E2 (PGE2) in regulation of its function: An in vivo approach

“…Additionally, taking into account the role of PRL as the main luteotrophic factor during the second half of canine diestrus, and the recently presented evidence showing increasing expression of its receptor during the early luteal phase [18], the expression of PRLR was investigated by assessing messenger RNA (mRNA) obtained from primary luteal cells isolated during the early luteal phase, which had been treated with PGE2 in previous experiments [13].…”

The Dog: Nonconformist, Not Only in Maternal Recognition Signaling

“…Following placentation, a further increase in PRLR was noticed and appeared to be specifi c to the invasion sites, as concluded from its lower expression at interplacental sites (Kowalewski et al 2011b ). In addition to the epithelial components of uterine structures, it was localized in trophoblast cells.…”

“…Thus, the uterus does not seem to contribute strongly to the overall circulating PRL in the dog. However, the highly upregulated PRLR expression (Kowalewski et al 2011b ;Kautz et al 2014 ) could serve to compensate for low PRL expression and thereby to locally increase its relative availability. The expression of LH receptor, which was recently suggested to be involved in implantation in mice (Gridelet et al 2013 ), was signifi cantly reduced in the early pregnant canine uterus (Kautz et al 2014 ).…”

“…A more general defi nition appears more suitable for this species, designating the maternal recognition as a morphological and functional relationship between the uterus, the embryo, and the corpus luteum (CL) which is the sole source of progesterone in the dog (Concannon et al 1989 ). The more intimate embryo-and feto-maternal contact starting following implantation and placentation is important for maintenance of pregnancy and also plays a role at term (Kowalewski et al 2010(Kowalewski et al , 2011bGram et al 2013Gram et al , 2014a.…”

<b>Papel da insulina sobre a esteroidogênese no corpo lúteo canino</b>

“…The prostaglandin E2 (PGE2) has been proposed as one of the most important luteotrophic factors during CL formation, i.e., during the first third of diestrus and it acts in an autocrine and/or paracrine manner (KOWALEWSKI et al, 2008;KOWALEWSKI et al, 2011). During the second half of diestrus, prolactin (PRL) is the main luteotrophic factor and its role is to sustain CL function and/or slowing down luteal regression (KOWALEWSKI, 2014).…”