Placental contribution to the endocrinology of gestation and parturition

Abstract

In addition to many other functions, the placenta is a source of a vast number of autocrine, paracrine and endocrine factors. However, the spectrum of placental regulatory factors, their concentrations, gestational profiles and roles may differ considerably even between phylogenetically closely related species. Depending on the species, placental regulatory factors of a broad range of molecule classes have been found including (glyco-)proteins, peptides, steroids and prostaglandins. Local placental regulatory factors are especially important for the dialogue between the fetal and the maternal compartment immediately at the feto-maternal borderline and for the control of growth, differentiation and functions of the placenta itself. Moreover, placental hormones in a proper sense may also have effects in more remote targets within the maternal compartment, serving functions such as pregnancy-specific adaptations of maternal circulation, provision of hemotrophe to the fetus or the development and function of the mammary gland. Functions of placental hormones in the fetus proper are less clear but may be especially important before the establishment of a functional fetal endocrine system and near term within the highly species-specific networks of signals preparing and initiating parturition. This review takes a comparative view on the situation in different domestic animals focusing on ruminants and on placental hormones occurring at significant concentrations in the maternal circulation.

Keywords: gonadotrophins; placenta; placental lactogen; relaxin; steroids..

Figure 1. Mature bovine binucleate trophoblast giant cell (TGC) invading the caruncular epithelium (CE; lower part of the micrograph). The TGC is surrounded by several uninucleate trophoblast cells (UTCs). In the TGC cytoplasm numerous secretory granules (small arrows) are visible which are released into the maternal compartment after fusion of a TGC with an individual caruncular epithelial cell. In the secretory granules different signaling molecules have been detected, e.g. placental lactogen and prolactin-related protein-1. The feto-maternal borderline is labeled with arrowheads. FS: fetal stroma; FC: fetal capillaries. Gestation day 150; Bar = 10 μm.

Figure 2. Immunolabelling (green) of prolactin-related protein-I (PRP-I) in secretory granula of a bovine TGC. The two TGC nuclei (arrows) are devoid of immunostaining. Gestation day 110; Bar = 10 μm.

Figure 3. Concept of the endocrine events initiating parturition in the sheep (according to Whittle et al., 2001). For description see section: Initiation of parturition with in species with a prepartal collapse of placental progestogen production (sheep, horse) in the text.

Figure 4. Concept of the prepartal switch in ovine placental steroidogenesis resulting from the up-repulation of CYP17A1 expression in the trophoblast induced by the increase of fetal cortisol levels (see Fig. 3). Due to the minimal lyase activity of ruminant CYP17A1 on the ∆4-pathway, the collapse of placental progesterone synthesis does not result to a noteworthy extent from a direct conversion of progesterone into estrogens but rather from the channeling of the common precursor pregnenolone into the synthesis of estrogens via the ∆5-pathway of steroidogenesis. A considerable up-regulation of placental CYP17A1 expression and activity has also been demonstrated in prepartal cows (Schuler et al., 1994; 2006b; Shenavai et al., 2012). However, different from the substantial pre- and intrapartal increase of placental estrogens in sheep in cattle a considerable increase in maternal concentrations of placental estrogens does not occur near term. P450scc: cytochrome P450 side-chain-cleavage enzyme (CYP11A1); P450c17: 17α-hydroxylase-C17,20-lyase (CYP17A1); 3ß-HSD: 3ß-hydroxysteroid dehydrogenase-∆5/4-isomerase (HSD3B1); 17ß-HSD: 17ß-hydroxysteroid dehydrogenase (HSD17B); P450arom: aromatase (CYP19A1).

Figure 5. Concept of the initiation of parturition in cattle (according to Shenavai et al., 2012). Prepartal endocrine changes similar to the sheep have been confirmed in the prepartal cow (see Fig. 4 and 5). However, different from the late pregnant sheep with the placenta as the only relevant source of progesterone, in cattle the corpus luteum is the predominant source of progesterone throughout gestation and the prepartal decline in maternal progesterone level is clearly associated with luteolysis.