Spermatogonial stem cells divide throughout life, maintaining their own population and giving rise to differentiated gametes. The unstable regulatory protein Geminin is thought to be one of the factors that determine whether stem cells continue to divide or terminally differentiate. Geminin regulates the extent of DNA replication and is thought to maintain cells in an undifferentiated state by inhibiting various transcription factors and chromatin remodeling proteins. To examine how Geminin might regulate spermatogenesis, we developed two conditional mouse models in which the Geminin gene (Gmnn) is deleted from either spermatogonia or meiotic spermatocytes. Deleting Geminin from spermatogonia causes complete sterility in male mice. Gmnn(-/-) spermatogonia disappear during the initial wave of mitotic proliferation that occurs during the first week of life. Gmnn(-/-) spermatogonia exhibit more double-stranded DNA breaks than control cells, consistent with a defect in DNA replication. They maintain expression of genes associated with the undifferentiated state and do not prematurely express genes characteristic of more differentiated spermatogonia. In contrast, deleting Geminin from spermatocytes does not disrupt meiosis or the differentiation of spermatids into mature sperm. In females, Geminin is not required for meiosis, oocyte differentiation, or fertility after the embryonic period of mitotic proliferation has ceased. We conclude that Geminin is absolutely required for mitotic proliferation of spermatogonia but does not regulate their differentiation. Our results suggest that Geminin maintains replication fidelity during the mitotic phase of spermatogenesis, ensuring the precise duplication of genetic information for transmission to the next generation.

In many organisms early development is under control of the maternal genome and zygotic gene expression is delayed until the mid-blastula transition (MBT). As zygotic transcription initiates, cell cycle checkpoints become activated and the tempo of cell division slows. The mechanisms that activate zygotic transcription at the MBT are incompletely understood, but they are of interest because they may resemble mechanisms that cause stem cells to stop dividing and terminally differentiate. The unstable regulatory protein Geminin is thought to coordinate cell division with cell differentiation. Geminin is a bi-functional protein. It prevents a second round of DNA replication during S and G2 phase by binding and inhibiting the essential replication factor Cdt1. Geminin also binds and inhibits a number of transcription factors and chromatin remodeling proteins and is thought to keep dividing cells in an undifferentiated state. We previously found that the cells of Geminin-deficient Xenopus embryos arrest in G2 phase just after the MBT then disintegrate at the onset of gastrulation. Here we report that they also fail to express most zygotic genes. The gene expression defect is cell-autonomous and is reproduced by over-expressing Cdt1 or by incubating the embryos in hydroxyurea. Geminin deficient and hydroxyurea-treated blastomeres accumulate DNA damage in the form of double stranded breaks. Bypassing the Chk1 pathway overcomes the cell cycle arrest caused by Geminin depletion but does not restore zygotic gene expression. In fact, bypassing the Chk1 pathway by itself induces double stranded breaks and abolishes zygotic transcription. We did not find evidence that Geminin has a replication-independent effect on transcription. We conclude that Geminin is required to maintain genome integrity during the rapid cleavage divisions, and that DNA damage disrupts zygotic gene transcription at the MBT, probably through activation of DNA damage checkpoint pathways.

Among populations of the three-spined stickleback fish in Alaska, females appear to show two forms of sterility tolerance to infection by the diphyllobothriidean cestode Schistocephalus solidus. In contrast to sticklebacks in other regions of the northern hemisphere, female fish are capable of producing clutches of eggs despite supporting large parasite burdens. Nonetheless, nutrient loss to the parasite, coupled with the energetic demands of host reproduction, eventually curtails spawning among infected females. Host females in Walby Lake experience 'fecundity reduction' resulting from nutrient theft as a side effect of infection. In Scout Lake, infected females show 'fecundity compensation', an adaptive, inducible response allowing them to increase current fecundity to compensate for reduction or loss of future reproduction. This multi-year study of sticklebacks from each lake addresses two empirical questions for a better understanding of the dynamic interplay between host and parasite. First, is there is any annual variation within the two responses to parasitism in each host population; and, if so, is it related to parasite burden? Second, do the two host responses show consistent differences between the populations of sticklebacks despite any yearly variation in them? We found annual, intra-population variation within the response shown by each population of stickleback which appears to have been influenced by the parasite : host mass ratio and possibly by unknown environmental conditions affecting the reproductive physiology of stickleback females. Moreover, the data support the hypothesis that ovum mass is more sensitive to parasitism (parasite burden) than clutch size in females from Walby Lake which exhibit fecundity reduction. Notwithstanding the intra-population variation within each host response, the responses to infection occurred consistently within each respective stickleback population and appear to reflect stable, fundamental characteristics of the populations.

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Gender and sex minorities have been declared a health disparity by the NIH and discussions pertaining to inclusiveness of LGBTQI+ in medical curricula have soared. This study aimed at analyzing the current presentation of sex, reproductive anatomy and sexual function within gross anatomy, histology, embryology and neuroanatomy textbooks. Content analyses were performed using grounded theory approaches to measure the ideas and concepts presented by the authors about male, female and intersex anatomy, and also male, female and intersex sexual function. The analyses included breadth of topics covered, for example, whether or not the clitoris was included in the female reproduction chapter or whether or not female sexual function was described. Also, inclusive language pertaining to the anatomic variation in sexual anatomy and sexual function was noted as well as the devotion of words spent to each topic within the textbook chapter. In text that presented intersex and anatomic variation topics, a second content analysis was performed to describe the “inclusiveness” of the language used and presentation style when discussing individuals with atypical sex and/or gender anatomy and functioning. Overall, 6 gross anatomy, 9 histology, 5 embryology and 3 neuroanatomy textbooks were analyzed, some in a retrospective fashion to highlight changes in editions. Results indicate that there are inconsistent patterns of addressing sexual anatomy and functioning within textbooks of the anatomic sciences, with different fields (i.e. embryology versus gross anatomy) employing a different subset of approaches.