bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.05.01.651671

Fertility recovery after combined adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy in mice

Lu, X.·Turathum, B.·Chian, R.-C.·Liu, Y.
View original source ↗Export metadata ↓

Abstract

BackgroundWith combined adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy and radiotherapy, most of Hodgkin lymphoma (HL) patients were cured. The effect of ABVD treatment on ovarian reserve and fertility has not been fully characterized, and whether fertility preservation is required is controversial and not empirically known. MethodsEight-week-old female mice were injected intravenously with saline solution or ABVD for 4 weeks, respectively. Estrous cycles, level of serum anti-Mullerian hormone (AMH), body weight and ovary weight were recorded. Ovarian tissue structure and the number of follicles at each stage were analysed. IVF assay and natural mating trials were performed. Finally, transcriptome sequencing of ovarian tissue was conducted. ResultsMost mice completely lost their estrous cycle soon after ABVD injection. After 4 cycles of treatments, the body weight gain and gross ovarian weight were significantly lower than those of the control. However, estrous cycles were returned to normal at 4 weeks after ABVD discontinuation. Serum AMH and the numbers of primordial follicles were significantly increased compared to controls. ABVD withdrawal did not affect the rate of cleavage or blastocyst formation in IVF assays. Furthermore, the mice were fertile and there was no significant difference in offspring weight, but the number of offspring in the ABVD discontinuation group was smaller compared with the controls. Transcriptome analyses revealed that the JAK/STAT pathway, which is involved in the inhibition of primordial follicles activation and apoptosis, was upregulated in ABVD-treated ovaries, whereas few gene expressions were altered 4 weeks after ABVD withdrawal. ConclusionsThe ovarian reserve and reproductive function can be recovered after ABVD treatment, and combined ABVD treatment for a short time has a beneficial effect on the ovarian reserve, which can be used to provide a basis for guiding fertility preservation decision-making for HL patients. Statements and DeclarationsThe authors declare no competing interests.

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lu, X., Turathum, B., Chian, R.-C., Liu, Y.. 2025-05-07. Fertility recovery after combined adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy in mice. https://doi.org/10.1101/2025.05.01.651671

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Proteome-wide quantification of protein turnover in frog and fly embryos reveals divergent strategies of maternal inheritance

Every embryo inherits a maternal proteome that it must remodel with zygotic proteins to build its many cell types. The fate of the maternal proteome remains contested because indirect measurements cannot resolve it. Here, we combine 18O-water labeling with multiplexed proteomics to quantify protein turnover proteome-wide in frog and fly embryos. Through hatching, the frog preserves the bulk of its maternal proteome, confining rapid degradation to a small regulatory module. The fly cannot meet its synthesis demand from yolk alone and instead degrades nearly all maternal proteins, including housekeeping proteins long assumed stable, recycling them into new protein. Yet the turnover hierarchy is conserved, with disordered and regulatory proteins degrading fastest, while the fly rescales the whole proteome ~eightfold faster. These results recast the developmental proteome as both informational inheritance and metabolic reserve, establish 18O-water labeling as a turnover method for non-feeding organisms, and provide a resource of embryonic half-lives.

developmental biology↗
bioRxiv2026

The MAPK phosphatase VHP-1 buffers pharynx-to-body proportions against tissue-specific growth imbalance in C. elegans

Maintaining appropriate organ size ratios in the face of growth fluctuations is critical for the development of a reproducible body plan. Yet the mechanisms involved remain poorly understood. Here, we investigated how pharynx-to-body proportions are maintained in Caenorhabditis elegans, combining tissue-specific perturbations, genetic screening, and longitudinal live imaging. A genome-wide RNAi screen revealed that knock-down of the dual-specificity MAPK phosphatase VHP-1 turns animals hypersensitive to inter-tissue growth imbalance caused by pharyngeal or epidermal depletion of the mTORC1 activator RAGA-1 or the ribosomal protein RPL-22. In contrast, vhp-1 mutants tolerated global raga-1 loss, indicating a specific requirement for vhp-1 under tissue growth imbalance. Knock-down of the p38 pathway suppressed the imbalance-specific defects of vhp-1 mutants. In contrast, JNK knock-down effectively rescued the pleiotropic phenotypes of vhp-1 mutants but only weakly reduced their sensitivity to RAGA-1 imbalance, indicating that these two stress-MAPK pathways make distinct contributions to the response to growth imbalance. Finally, whole-animal VHP-1 levels increased upon epidermal RAGA-1 depletion, and epidermal VHP-1 depletion did not reproduce the sensitivity caused by global vhp-1 loss, consistent with a contribution from VHP-1 outside the growth-perturbed epidermis in buffering against local growth imbalance.

developmental biology↗
bioRxiv2026

Network topology reveals distinct forms of developmental leverage in the Drosophila wing

Developmental gene regulatory networks reliably transform positional information into complex multicellular form, yet the organizational principles linking network architecture to developmental mechanism remain poorly understood. Here, we analyzed the Drosophila melanogaster wing developmental network to determine whether network topology reflects the distribution of developmental leverage during organogenesis. Integration of curated wing-development genes with high-confidence STRING interactions revealed five Hierarchical Layers of Developmental Control (HLDCs) associated with distinct topological and developmental roles. Organizer Centers, Signaling Scaffolds, and Pattern Implementers formed a forward-specification axis in which connectivity progressively contracted as positional information was transformed into increasingly localized developmental programs. Interface Coordinators departed from this hierarchy through disproportionate brokerage, whereas Local Modulators retained connectivity despite localized developmental scope. We propose that these complementary signatures reflect two regulatory architectures: 1) hierarchical information propagation that generates developmental identity and 2) distributed homeostatic regulation that coordinates and refines developmental outputs. Within Character Identity Modules (ChiMOs), this architecture links conserved patterning systems, Hox-defined contexts, and organ-specific kernels to reproducible morphology, providing a mechanistic hypothesis for developmental canalization and experimentally testable predictions.

developmental biology↗