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International audience; The potential for evolutionary change is deeply anchored in the kind and amount of heritable phenotypic variation that organisms can produce, and thus in the way that genetic predispositions translate into the phenotype. That translation is the genotype-phenotype (GP) map. Here, we first explain the two common conceptualizations of GP map: the global correspondence map and the local mechanistic map, and how they relate to each other. We focus on the structural aspects of the GP mapping, as summarized in the notions of pleiotropy and epistasis, and argue that their effect on evolvability is not captured sufficiently in the current theory. One way to approach this problem is to address mechanistic, causal mapping explicitly and explore systematically the variational properties of various well-known biochemical or regulatory processes. This may allow us not only to better account for the effects of pleiotropy and epistasis, but to potentially complement these summarizing concepts themselves with notions that better capture the underlying mechanisms-thus adding to the mechanistic aspect to the global GP map.

The question of how to conceive of the relation between the pregnant female and the embryo has become a recent focus of debate in the philosophical literature. Here we consider this problem in the context of current debates on individuality in the philosophy of biology by looking at how pregnancy is individuated in different disciplinary contexts. Firstly, we review different notions of biological individuality in the literature, examine how each of them applies to the case of pregnancy, and claim that recent work on the evolution of eutherian reproduction offers insights for new criteria for rethinking the individuality of pregnancy. Then, we reconstruct the main assumptions underlying the established biological account of pregnancy. Finally, we develop an alternative account based on the hypothesis that pregnancy is an evolved relational novelty and maintain that pregnant females are conceived as historical reproductive individuals. In the final section before the conclusions, we discuss how the historical reproductive biological individuality of pregnancy differs from, and coexists with, other views of individuality, and examine some of its consequences.

In human pregnancy, recognition of an embryo within the uterus is essential to support the fetus through gestation. In non-macropodid marsupials, such as the opossums, pregnancy is shorter than the oestrous cycle and the steroid hormone profile during pregnancy and oestrous cycle are indistinguishable. For these reasons, it was assumed that recognition of pregnancy, as a trait, evolved in the eutherian (placental) stem lineage and independently in wallabies and kangaroos. To investigate whether uterine recognition of pregnancy occurs in species with pregnancy shorter than the oestrous cycle, we examined reproduction in the short-tailed opossum (Monodelphis domestica), a marsupial with a plesiomorphic mode of pregnancy. We examined the morphological and gene expression changes in the uterus of females in the non-pregnant oestrous cycle and compared these to pregnancy. We found that the presence of an embryo did not alter some aspects of uterine development but increased glandular activity. Transcriptionally, we saw big differences between the uterus of pregnant and cycling animals. These differences included an upregulation of genes involved in transport, inflammation and metabolic-activity in response to the presence of a fetus. Furthermore, transcriptional differences reflected protein level differences in transporter abundance. Our results suggest that while the uterus exhibits programmed changes after ovulation, its transcriptional landscape during pregnancy responds to the presence of a fetus and upregulates genes that may be essential for fetal support. These results are consistent with endometrial recognition of pregnancy occurring in the opossum. While the effects on maternal physiology appear to differ, recognition of pregnancy has now been observed in eutherian mammals, as well as, Australian and American marsupials.

Figure S1. In late pregnancy (A) and the equivalent time in the estrous cycle (D), the uterus becomes highly folded with few endometrial glands within these folds. In post-attachment pregnancy the endometrial glands are open, and glandular epithelial cells appear secretory in form (B), while in the equivalent stage of the estrous cycle, the glands are shrunken, compact, and glandular epithelial cells have shrunk in size (E). Towards the end of pregnancy the sub-epithelial stromal cell population is displaced and replaced by a network of sub-epithelial capillaries (C), however, in the estrous cycle, this epithelial cell population remains compact (F) which may prevent the formation of the sub-epithelial capillary network.; Figure S2.(A) Significantly over-represented gene ontology terms from the list of significantly down-regulated genes in estrous cycle (13 dpe) compared to non-reproductive uterus. (B) Significantly over-represented gene ontology terms from the list of significantly down-regulated genes in late gestation uterus compared to the estrous cycle.; Figure S3. (A) Significantly over-represented gene ontology in genes up-regulated in EMG compared to NR. (B) Significantly over-represented gene ontology in genes down-regulated in EMG compared to NR.

Supplemental Material, Supplemental_Figuresand for Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs by Kalle T. Rytkönen, Eric M. Erkenbrack, Matti Poutanen, Laura L. Elo, Mihaela Pavlicev, and Günter P. Wagner in Reproductive Sciences