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Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species and speciation. Male germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition and have been subject to evolutionary divergence among mammals. However, the mechanisms underlying germline regulatory divergence remain undetermined. Here, we show that endogenous retroviruses (ERVs) influence species-specific germline transcriptomes. After the mitosis-to-meiosis transition in male mice, specific ERVs function as active enhancers to drive germline genes, including a mouse-specific gene set, and bear binding motifs for critical regulators of spermatogenesis, such as A-MYB. This raises the possibility that a genome-wide transposition of ERVs rewired germline gene expression in a species-specific manner. Of note, independently evolved ERVs are associated with the expression of human-specific germline genes, demonstrating the prevalence of ERV-driven mechanisms in mammals. Together, we propose that ERVs fine-tune species-specific transcriptomes in the mammalian germline.

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

It has been hypothesized that one of the main reasons evolution has been able to produce such impressive adaptations is because it has improved its own ability to evolve -- "the evolution of evolvability". Rupert Riedl, for example, an early pioneer of evolutionary developmental biology, suggested that the evolution of complex adaptations is facilitated by a developmental organization that is itself shaped by past selection to facilitate evolutionary innovation. However, selection for characteristics that enable future innovation seems paradoxical: natural selection cannot favor structures for benefits they have not yet produced, and favoring characteristics for benefits that have already been produced does not constitute future innovation. Here we resolve this paradox by exploiting a formal equivalence between the evolution of evolvability and learning systems. We use the conditions that enable simple learning systems to generalize, i.e., to use past experience to improve performance on previously unseen, future test cases, to demonstrate conditions where natural selection can systematically favor developmental organizations that benefit future evolvability. Using numerical simulations of evolution on highly epistatic fitness landscapes, we illustrate how the structure of evolved gene regulation networks can result in increased evolvability capable of avoiding local fitness peaks and discovering higher fitness phenotypes. Our findings support Riedl's intuition: Developmental organizations that "mimic" the organization of constraints on phenotypes can be favored by short-term selection and also facilitate future innovation. Importantly, the conditions that enable the evolution of such surprising evolvability follow from the same non-mysterious conditions that permit generalization in learning systems.