Lamina-associated polypeptide 1 (LAP1) is a type II transmembrane protein of the inner nuclear membrane encoded by the human gene TOR1AIP1. LAP1 is involved in maintaining the nuclear envelope structure and appears be involved in the positioning of lamins and chromatin. To date, LAP1’s precise function has not been fully elucidated but analysis of its interacting proteins will permit unraveling putative associations to specific cellular pathways and cellular processes. By assessing public databases it was possible to identify the LAP1 interactome, and this was curated. In total, 41 interactions were identified. Several functionally relevant proteins, such as TRF2, TERF2IP, RIF1, ATM, MAD2L1 and MAD2L1BP were identified and these support the putative functions proposed for LAP1. Furthermore, by making use of the Ingenuity Pathways Analysis tool and submitting the LAP1 interactors, the top two canonical pathways were “Telomerase signalling” and “Telomere Extension by Telomerase” and the top functions “Cell Morphology”, “Cellular Assembly and Organization” and “DNA Replication, Recombination, and Repair”. Once again, putative LAP1 functions are reinforced but novel functions are emerging.

Spermatogenesis comprises highly complex differentiation processes. Nuclear envelope (NE) proteins have been associated with these processes, including lamins, lamina-associated polypeptide (LAP) 2 and the lamin B-receptor. LAP1 is an important NE protein whose function has not been fully elucidated, but several binding partners allow predicting putative LAP1 functions. To date, LAP1 had not been associated with spermatogenesis. In this study, LAP1 expression and cellular/subcellular localization during spermatogenesis in human and mouse testes is established for the first time. The fact that LAP1 is expressed during nuclear elongation in spermiogenesis and is located at the spermatids’ centriolar pole is singularly important. LAP1 binds to members of the protein phosphatase 1 (PP1) family. Similar localization of LAP1 and PP1γ2, a testis-specific PP1 isoform, suggests a shared function for both proteins during spermiogenesis. Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via interaction with acetylated α-tubulin and lamins, respectively. Taken together, the present results indicate that, by moving to the posterior pole in spermatids, LAP1 can contribute to the achievement of non-random, sperm-specific chromatin distribution, as well as modulate cellular remodeling during spermiogenesis. In addition, LAP1 seems to be associated with dynamic microtubule changes related to manchette formation and flagella development.

In medicine, safety and efficacy are the two pillars on which the implementation of novel treatments rest. To protect the patient from unnecessary or unsafe treatments, usually, a stringent path of (pre) clinical testing is followed before a treatment is introduced into routine patient care. However, in reproductive medicine several techniques have been clinically introduced without elaborate preclinical studies. Moreover, novel reproductive techniques may harbor safety risks not only for the patients undergoing treatment, but also for the offspring conceived through these techniques. If preclinical (animal) studies were performed, efficacy and functionality the upper hand. When a new medically assisted reproduction (MAR) treatment was proven effective (i.e. if it resulted in live birth) the treatment was often rapidly implemented in the clinic. For IVF, the first study on the long-term health of IVF children was published a decade after its clinical implementation. In more recent years, prospective follow-up studies have been conducted that provided the opportunity to study the health of large groups of children derived from different reproductive techniques. Although such studies have indicated differences between children conceived through MAR and children conceived naturally, results are often difficult to interpret due to the observational nature of these studies (and the associated risk of confounding factors, e.g. subfertility of the parents), differences in definitions of clinical outcome measures, lack of uniformity in assessment protocols and heterogeneity of the underlying reasons for fertility treatment. With more novel MARs waiting at the horizon, there is a need for a framework on how to assess safety of novel reproductive techniques in a preclinical (animal) setting before they are clinically implemented. In this article, we provide a blueprint for preclinical testing of safety and health of offspring generated by novel MARs using a mouse model involving an array of tests that comprise the entire lifespan. We urge scientists to perform the proposed extensive preclinical tests for novel reproductive techniques with the goal to acquire knowledge on efficacy and the possible health effects of to-be implemented reproductive techniques to safeguard quality of novel MARs.

The main form of intracellular protein glycosylation (O-GlcNAc) is reversible and has been mapped on thousands of cytoplasmic and nuclear proteins, including RNA polymerase II, transcription factors, and chromatin modifiers. The O-GlcNAc modification is catalyzed by a single enzyme known as O-GlcNAc Transferase, that is required for mammalian early development. Yet, neither the regulatory function of protein O-GlcNAcylation in the embryo nor the embryonic O-GlcNAc proteome have been documented. Here, we devised a strategy to enzymatically remove O-GlcNAc from preimplantation embryonic nuclei, where this modification accumulates coincidently with embryonic genome activation (EGA). Unexpectedly, the depletion of nuclear O-GlcNAc to undetectable levels has no impact on EGA, but dampens the transcriptional upregulation of the translational machinery, and triggers a spindle checkpoint response. These molecular alterations were phenotypically associated with a developmental delay starting from early cleavage stages and persisting after embryo implantation, establishing a link between nuclear glycosylation and the pace of embryonic development.