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. 2012 Aug;79(8):564-72.
doi: 10.1002/mrd.22062. Epub 2012 Jul 9.

Plac1 (placenta-specific 1) is essential for normal placental and embryonic development

Suzanne M Jackman  1 , Xiaoyuan Kong, Michael E Fant
Affiliations

Plac1 (placenta-specific 1) is essential for normal placental and embryonic development

Suzanne M Jackman et al. Mol Reprod Dev. 2012 Aug.

Abstract

Plac1 is a recently identified, X-linked gene whose expression is restricted primarily to cells of the trophoblast lineage. It localizes to a chromosomal locus previously implicated in placental growth. We therefore sought to determine if Plac1 is necessary for placental and embryonic development by examining a mutant mouse model. Plac1 ablation resulted in placentomegaly and mild intrauterine growth retardation (IUGR). At E16.5, knockout (KO) and heterozygous (Het) placentae of the Plac1-null allele inherited from the mother (X(m-) X) weighed approximately 100% more than wildtype (WT) placentae, whereas the corresponding embryos weighed 7-12% less. Histologically, Plac1 mutants exhibited an expanded spongiotrophoblast layer that invaded the labyrinth. By contrast, Het placentae that inherited the null allele from the father (XX(p-) ) exhibited normal growth and were histologically indistinguishable from WT placentae, consistent with paternal imprinting of Plac1. When examined across gestation, WT and X(m-) X placental weights peaked at E16.5 and decreased slightly thereafter. KO placentae (X(m-) X(p-) and X(m-) Y), however, continued to increase in weight after E16.5, consistent with a functional role for the paternal Plac1 allele. Subsequent analysis confirmed that the paternal allele partially escapes complete X-inactivation and thus contributes to placental growth regulation. Additionally, although male Plac1 KO mice can survive, they exhibit decreased viability as a consequence of events occurring late in gestation or shortly after birth. Thus, Plac1 is a paternally imprinted, X-linked gene essential for normal placental and embryonic development.

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Figures

Figure 1
Figure 1
Plac1 ablation results in placentomegaly and apparent intrauterine growth retardation (IUGR). Gross appearance of a typical Het (Xm-X) placenta and embryo at E16.5 is illustrated. WT placenta = 103 mg; Xm-X placenta = 215 mg
Figure 2
Figure 2
Histological appearance of Plac1 mutant placentae. Periodic acid-Schiff (PAS) stain of paraffin-embedded placentae obtained at E16.5 (magnification = 1.5×).
Figure 3
Figure 3
Spongiotrophoblasts in WT and Plac1-mutant placentae. In situ hybridization of Prl8a8 expression using a digoxygenin detection system, as described in “Materials and Methods”. Non-specific signal was determined by hybridization with the “sense” riboprobe construct (magnification = 1.5×).
Figure 4
Figure 4
Trophoblast giant cells (TGC) in WT and Plac1-mutant placentae. In situ hybridization of Prl2c2 expression using the digoxygenin detection system, as described in “Materials and Methods”. Black arrows = parietal TGCs adjacent to the decidua; Green arrow = sinusoidal TGCs; Red arrow = SpT at the interface of the junctional zone and labyrinth. Non-specific signal was determined by hybridization with the “sense” riboprobe construct. Magnification = 1.5×.
Figure 5
Figure 5
Placental and embryonic growth dynamics. Placental and embryonic weights were determined throughout gestation as a function of WT, Xm-X, and KO genotypes. WT and KO data include both male and female embryos. A. Placental weights (mean ± SD), with the number assessed (n) indicated in parentheses. B. Embryonic weights (mean ± SD); *, P = 0.041 (difference between Het and WT at E16.5).
Figure 6
Figure 6
Post-natal growth of Plac1 mutants. The weights of male Plac1-KO and WT mice were determined at weaning (3 weeks) and followed for 4 months. The number assessed (n) indicated in parentheses.
Figure 7
Figure 7. Paternal expression of Plac1
Plac1 mRNA expression was determined by quantitative RT-PCR in placentae of female WT and Xm-X littermates. Plac1 expression was normalized against 18S ribosomal RNA, and shown in arbitrary units. A KO placenta from a separate litter was included as a negative control.
Figure 8
Figure 8
Plac1 expression in murine placenta. In situ hybridization of Plac1 mRNA at E12.5 using a digoxygenin detection system, as described in “Materials and Methods”. A–B: WT placenta. C–D: Xm-X heterozygous placenta. SpT = spongiotrophoblasts. Non-specific hybridization was identified using a probe in the “sense” orientation.
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