Placental Lactogen

BackgroundThe Prolactin (PRL) hormone gene family shows considerable variation among placental mammals. Whereas there is a single PRL gene in humans that is expressed by the pituitary, there are an additional 22 genes in mice including the placental lactogens (PL) and Prolactin-related proteins (PLPs) whose expression is limited to the placenta. To understand the regulation and potential functions of these genes, we conducted a detailed temporal and spatial expression study in the placenta between embryonic days 7.5 and E18.5 in three genetic strains.ResultsOf the 22 PRL/PL genes examined, only minor differences were observed among strains of mice. We found that not one family member has the same expression pattern as another when both temporal and spatial data were examined. There was also no correlation in expression between genes that were most closely related or between adjacent genes in the PRL/PL locus. Bioinformatic analysis of upstream regulatory regions identified conserved combinations (modules) of putative transcription factor binding sites shared by genes expressed in the same trophoblast subtype, supporting the notion that local regulatory elements, rather than locus control regions, specify subtype-specific expression. Further diversification in expression was also detected as splice variants for several genes.ConclusionIn the present study, a detailed temporal and spatial placental expression map was generated for all murine PRL/PL family members from E7.5 to E18.5 of gestation in three genetic strains. This detailed analysis uncovered several new markers for some trophoblast cell types that will be useful for future analysis of placental structure in mutant mice with placental phenotypes. More importantly, several main conclusions about regulation of the locus are apparent. First, no two family members have the same expression pattern when both temporal and spatial data are examined. Second, most genes are expressed in multiple trophoblast cell subtypes though none were detected in the chorion, where trophoblast stem cells reside, or in syncytiotrophoblast of the labyrinth layer. Third, bioinformatic comparisons of upstream regulatory regions identified predicted transcription factor binding site modules that are shared by genes expressed in the same trophoblast subtype. Fourth, further diversification of gene products from the PRL/PL locus occurs through alternative splice isoforms for several genes.

Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function.

Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet-despite human observational data spanning several decades-evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.

Smoking during pregnancy has many negative effects, such as growth retardation, premature birth, and placental detachment. However, although it is known to have negative effects during breastfeeding, it has not been examined in detail as the pregnancy period. This study aimed to investigate the effects of smoking during pregnancy on the placenta and its relationship with breastfeeding practices and placental hormone levels. The study included 70 women who underwent spontaneous vaginal delivery. The participants were divided into two groups: smokers (n = 35) and non-smokers (n = 35). The breastfeeding conditions of both groups were evaluated prior to discharge and on the 10th day, postpartum. Cross-sectional samples of placental tissues were collected, and their IGF-1, leptin, and HPL immunoreactivities were analyzed. A significant difference was found between the smoking status of the mothers and the immunoreactivity of IGF-1, leptin, and HPL (p < 0.05). Pregnant mothers who smoked showed lower expression of IGF-1, leptin, and HPL than non-smoker pregnant mothers. These results indicate that maternal smoking during pregnancy has adverse effects on the placenta and cord blood and may affect fetal development. Moreover, prenatal maternal smoking is associated with changes in breastfeeding practices.