An increasing number of vertebrate species are under threat of extinction, and conservation efforts are vital to the survival of many species. Knowledge of reproductive processes across taxa, and how different factors can impact reproductive success, is essential for supporting conservation breeding and mitigating threats to reproductive success of wild populations. Although historically much of our knowledge came from model species and more invasive techniques, non-invasive monitoring of biomarkers related to reproduction can be invaluable to monitor individuals and populations over prolonged periods, crucial to gaining fundamental knowledge on reproductive physiology across a wider range of species and locations, and for evidence-based management of reproduction. Advances over the last few decades have increased the sample types that can be used and the potential biomarkers that can be investigated, but the proportion of vertebrates to which these techniques have been applied remains relatively low. The aim of this review is to highlight some of the hormones and other biomarkers that can inform on reproductive function, the sample types and considerations for non-invasive monitoring, and where efforts are required to further our understanding of reproduction in both individuals and populations of wild vertebrates. Increased application of these techniques across species could not only improve the success of conservation efforts but also help to assess the increasing threats to reproduction, such as by endocrine disruptors in natural environments, that have the potential to impact all species on the planet.
Endometrosis is a chronic degenerative condition of the mare endometrium characterized by progressive fibrosis and glandular alterations that impair uterine function and fertility. Its pathogenesis involves persistent inflammation, the activation of myofibroblasts, and the accumulation of extracellular matrix (ECM), leading to disrupted glandular secretion and compromised maintenance of pregnancy. While histopathological studies of endometrosis are well described, the underlying molecular mechanisms remain incompletely understood. Emerging evidence highlights the crucial role of epigenetic regulation, particularly DNA methylation, non-coding RNAs (ncRNA), and histone modifications in modulating the gene networks that drive fibrosis. Altered DNA methylation patterns in key profibrotic and antifibrotic genes modulate collagen deposition and ECM turnover, while specific ncRNAs regulate genes involved in fibrotic and inflammatory pathways. Recent studies suggest that endometrosis progression in mares is accompanied by dynamic changes in the epigenetic landscape of both the endometrium and myometrium, highlighting the role of epigenetic regulation in this condition. This review synthesizes current knowledge on the epigenetic mechanisms implicated in mare endometrosis, focusing on DNA methylation-mediated regulation of fibrosis-related genes, histone modification, and changes in ncRNA expression in endometrium and/or myometrium during the progression of fibrotic changes, and their impact on the pathogenesis of this condition. Understanding these molecular processes is essential for identifying novel diagnostic biomarkers and developing targeted therapies to improve reproductive outcomes in affected mares.
The quality of oocytes is crucial for embryonic development. The morphology of cumulus-oocyte complexes (COCs) and cumulus expansion are widely used indicators of oocyte quality; however, quantitative evidence is limited. We investigated the potential of assessing the quality of COCs based on their objective morphological characteristics and the impact of cumulus expansion on bovine in vitro-produced embryo development. COCs were graded before in vitro maturation (IVM) according to the International Embryo Technology Society (IETS) standards, and their morphological characteristics (area, perimeter, circularity, and solidity) were measured. The cumulus expansion rate and nuclear maturation were then evaluated after IVM. Decision tree models were developed based on COC morphology to classify COC grades and predict the cumulus expansion rate. In another experiment, COCs were divided into two groups based on a 100% cumulus expansion threshold, and embryonic development was assessed. The results revealed that the morphological characteristics of COCs were associated with the IETS grades and cumulus expansion rate but not with nuclear maturation. The predictive models for cumulus expansion capacity achieved an accuracy of 75.5%. COCs with greater cumulus expansion exhibited a significantly higher proportion of ≥ eight-cell-stage embryos on day 2 (14.0 ± 5.9%, P < 0.05). However, the blastocyst formation rate did not differ according to the extent of cumulus expansion. These findings indicate that an objective morphological assessment can predict cumulus expansion capacity and may provide a non-invasive and reproducible approach for selecting high-quality COCs before IVM, potentially indicating an association with the speed of early embryonic development.
Review of the primary literature was used to develop six propositions regarding the nature of actions of heat stress on fertility of the bovine female. The first two propositions are that the reduction in fertility caused by heat stress is due to 1) negative effects on the competence of the oocyte to be fertilized and 2) support embryonic development and death of the embryo when exposed to elevated temperature. The third proposition is that it remains unclear whether damage to the spermatozoa occurs after deposition in the reproductive tract of a heat-stressed female. Fourth, the embryo acquires resistance to heat stress after activation of the embryonic genome. Fifth, heat stress after the first few days of pregnancy usually has only slight effects on embryonic or fetal survival. Sixth, the magnitude of effects of heat stress on fertility is related to the degree of hyperthermia experienced by the female. Thus, physiological and environmental factors that control ability of an animal to regulate its body temperature during heat stress are important determinants of the magnitude of the impact of heat stress on fertility.
Buffalo is a vital livestock species in tropical and subtropical regions, contributing significantly to milk, meat, draught power, and rural livelihoods. Various reproductive biotechnologies have been explored to enhance the productivity and genetic merit of buffalo populations. Among these, somatic cell nuclear transfer (SCNT) has emerged as a promising tool for the multiplication of elite germplasm and the preservation of valuable genetic resources. Since the birth of the world's first cloned water buffalo in 2009, substantial progress has been made to improve the efficiency of SCNT through optimization of donor cell types, oocyte and embryo culture systems, and the application of epigenetic modifiers to overcome reprogramming barriers. India alone has reported the successful production of more than 30 cloned buffaloes, while other countries have also documented encouraging outcomes. The integration of SCNT with modern genome editing technologies offers a transformative opportunity for precision breeding in buffalo. Although studies in buffalo genome editing remain limited compared to cattle, recent breakthroughs-the first successful birth of a genome-edited (MSTN gene knockout) buffalo-demonstrate the feasibility and future potential of this combined approach. In conclusion, the convergence of SCNT and genome editing represents a powerful platform for advancing buffalo genetic improvement programs, with the potential to substantially strengthen buffalo husbandry and productivity in tropical nations.
'Beef-on-dairy' describes the strategic use of beef semen on dairy females that are not required to produce replacement heifers. Adoption of beef-on-dairy systems has increased rapidly in recent years, enabled by the growth in use of sex-sorted semen to generate replacement females. This shift presents both opportunities and challenges: the rate of genetic gain can be accelerated, but the supply of high genetic merit male dairy calves will need to be generated through alternative means, and there will be an increased requirement for beef sires specifically suited for mating with dairy females. Assisted reproductive technologies, including sex-sorted semen and embryo-based approaches, offer considerable potential to enhance the genetic merit of both dairy and beef sires. When applied strategically, these technologies can accelerate genetic progress in dairy herds and improve the beef value of surplus calves born. The implementation of these technologies is challenging in seasonal-calving systems, however, and use of sex-sorted semen and embryo technologies must be carefully managed. In addition, the availability of suitable donor and recipient animals for embryo production and transfer is inherently seasonal, creating logistical constraints. Despite these challenges, more effective integration of dairy and beef breeding strategies offers substantial benefits. These include improved biological and economic efficiency of pasture-based milk and beef production, reductions in waste and animal welfare concerns, and the delivery of higher-value beef products. Ultimately, the strategic alignment of dairy and beef breeding decisions represents a key opportunity to enhance the sustainability, resilience and societal value of modern livestock production systems.
The efficiency of reproductive technologies in buffalo is limited by the low number of competent oocytes and the reduced oocyte competence during the non-breeding season, impacting on embryo production costs. This review focuses on the factors influencing oocyte developmental competence in buffalo, emphasizing the role of season and its effects on the follicular environment. Studies integrating transcriptomic, miRNA and metabolomic analyses revealed that the decreased oocyte competence recorded during the non-breeding season is associated with altered expression of genes and miRNAs involved in energy metabolism, oxidative balance, homeostasis and inflammatory status, as well as in changes in the cargo of the extracellular vesicles within the follicular fluid, resulting in variations in the metabolites content of the follicle. These molecular shifts reflect a state of negative energy balance and oxidative stress that may affect oocyte competence and embryo development. Corrective strategies have been proposed to counteract these effects, including dietary supplementation with green tea extract, which enhances follicular growth, antioxidant capacity and oocyte competence and the in vitro addition of extracellular vesicles from the breeding season, which improves embryo yields from oocytes collected during the non-breeding season. These findings highlight that multiple factors play a role in the acquisition of oocyte competence and demonstrate that a multi-omic integrated approach may allow the identification of biomarkers and the design of in vivo and in vitro interventions to improve reproductive efficiency in buffalo.
Human activity is driving a biodiversity crisis marked not only by accelerating species extinctions but also by rapid erosion of genetic and phylogenetic diversity. De-extinction science has emerged in response. Here, we synthesize de-extinction as a conservation workflow that integrates ancient and museum genomics, comparative genome analysis, high-precision genome engineering, stem cell platforms, advanced assisted reproductive technologies (ART), emerging ex-utero gestation systems, and AI-enabled ecological modelling and monitoring. We frame three primary conservation applications: (i) reconstruction of lost ecological functions via engineered de-extinct species, (ii) genetic rescue and de-endangerment through restoration of lost diversity, repair of deleterious alleles, and enhancement of adaptive potential in living species, and (iii) acceleration of enabling technologies, particularly ART and stem cell capabilities, that remove reproductive bottlenecks in threatened taxa. Recent advances in sequencing and assembly now support high-quality genomes from extinct and archival material (e.g., thylacine, mammoth, dodo), enabling identification of functionally relevant variation, much of which resides in regulatory landscapes rather than coding sequence alone. In parallel, next-generation editing systems (base, prime, twinPE and large-fragment integration approaches) are shifting the field from single-variant correction to systematic rewriting of loci and regulatory modules, supported by long-read validation and stringent cell-line quality control. We discuss complementary cellular routes (somatic cells and pluripotent stem cells), the promise of in vitro gametogenesis and synthetic embryo models, and the potential of artificial gestation to overcome surrogate scarcity and interspecies incompatibility. Finally, we highlight rewilding as the decisive endpoint, requiring adaptive management, Indigenous partnership, and high-fidelity AI-assisted monitoring. Taken together, de-extinction is best understood as a technology engine for conservation, one that expands the actionable toolkit for preventing extinctions, restoring resilience, and rebuilding lost biodiversity.
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for normal reproductive function in mammals. GnRH pulses from the hypothalamus drive pulsatile gonadotropin release from the anterior pituitary, thereby regulating gonadal activity. Classic studies in rhesus monkeys have demonstrated that intermittent physiological GnRH administration maintains luteinizing hormone and follicle-stimulating hormone secretion, whereas continuous infusion suppresses pituitary responsiveness, establishing the necessity of pulsatile GnRH release. The neural mechanism governing this rhythmic secretion is termed the GnRH pulse generator, a master regulator of the hypothalamus-pituitary-gonadal axis. The debate over its origin was resolved following the discovery of kisspeptin. Evidence from goats and genetically modified rodents indicates that kisspeptin neurons in the arcuate nucleus-termed KNDy neurons because they co-express kisspeptin, neurokinin B (NKB), and dynorphin A (Dyn)-constitute the GnRH pulse generator. NKB exerts stimulatory effects, whereas Dyn exerts inhibitory effects; their coordinated actions generate rhythmic GnRH release. GnRH pulse generator activity integrates diverse internal and external cues. Nutritional deficiency, inflammatory stress, and seasonal photoperiod suppress pulse frequency, whereas pheromonal stimuli, such as the male effect in ruminants, activate it. Central metabolic and neuroendocrine signals, including neuropeptide Y, cholecystokinin, melanocortin pathways, and serotonin, further modulate generator activity, linking energy balance and reproduction. Targeting these regulatory pathways offers promising strategies for artificial reproductive control in livestock and potentially wildlife, highlighting the GnRH pulse generator as a critical therapeutic and management target.
Extensive DNA methylation and small non-coding RNA modifications occur during male germline differentiation, which are essential for normal spermatogenesis and sperm maturation. Recent evidence has underscored the role of these key regulators in male fertility. However, due to significant environmental and technical variations across the studies, the identification of epigenetic biomarkers relevant to fertility remains challenging. Nevertheless, recent studies using large cohorts and integrative approaches have highlighted sperm epigenetic signatures that improve fertility prediction. In addition, sperm-borne epigenetic marks have been proposed to influence early embryo development and offspring phenotype, supporting the concept of non-genetic inheritance across generations. In breeding sectors and particularly in cattle, while artificial insemination enables the dissemination of paternal genetics at the populational level, some of the broadly used reproductive biotechnologies may impact the sperm epigenetic profile. Therefore, deciphering sperm epigenetic mechanisms has become an important research topic for enhancing breeding efficiency. This review provides an overview of current knowledge on the bovine epigenetic dynamics in male germ cells, their association with fertility and their potential role in embryo development and offspring phenotype, with a focus on DNA methylation and small non-coding RNAs.
In this review, metabolic, endocrine and molecular dysregulation of canine pregnancy and parturition complications are discussed in a clinical context. The focus on metabolic and hormonal abnormalities of pregnancy includes gestational diabetes mellitus, pregnancy toxemia, hypocalcemia, luteal insufficiency and hypothyroidism, all with potential negative maternal and fetal outcomes. Gestational pseudo-Addisonian crisis, a rather infrequent but severe complication of canine pregnancy with yet unexplained pathophysiology is also presented. While most of these pregnancy complications have long been known, potential gaps in our understanding of their pathophysiology are shown. Complications during parturition affect 5-37% of all canine whelpings, posing a significant risk to the newborns and the mother. This review discusses recent advances about the pathophysiology of primary uterine inertia (PUI), which is the most frequently diagnosed type of dystocia in the bitch. A multifactorial origin of PUI is supported, although clear conclusions applicable to all cases cannot yet be drawn. Lower than normal maternal peripheral oxytocin and blood ionized calcium concentrations, as well as placental dysfunction resulting in decreased prostaglandin F2α production may be involved in its development. Furthermore, PUI has been linked to changes in the expression of several contractility-associated genes and proteins in the uterus, which may cause altered contractility, or alternatively and simultaneously reflect the time-dependent progression of labor. Future studies should focus on the interplay between the placenta, uterus, and the cervix to elucidate the underlying mechanical, endocrine and molecular mechanisms of PUI.
The preservation of chicken genetic resources is important to both backup commercial breeds that support egg and meat production worldwide and conserve the genetic diversity of indigenous breeds, which is essential for managing breeding according to future demands. Because chicken embryos are attached to a large yolk, cryopreservation is technically impossible. In chickens, a unique developmental engineering approach based on the manipulation of primordial germ cells (PGCs), the embryonic precursor cells of gametes, has been developed. Cryobanking of PGCs is an innovative strategy for efficiently maintaining chicken genetic resources without breeding live birds. Cryomedia containing dimethyl sulfoxide or propylene glycol (PG) as permeable cryoprotectants, combined with serum as a non-permeable cryoprotectant, have been widely used for the cryopreservation of chicken PGCs. However, because the serum composition varies greatly, performance differences arise between lots. Consequently, there is a demand for serum-free cryomedia with specific known compositions. Here, we investigated the cryoprotective effects of ovalbumin and sericin, as alternatives to serum, on chicken PGCs. Two cryomedia were designed: PO comprising 7.5% PG and 5% ovalbumin and PS comprising 7.5% PG and 2% sericin. Following the culture of PGCs cryopreserved in these cryomedia, viability and cell doubling times recovered to levels comparable to those of an unfrozen control group at 6 and 2 d post-culture, respectively. When frozen-thawed PGCs were transplanted, their gonadal migration ability was significantly lower immediately after thawing, but recovered to levels comparable to those of the unfrozen control group after 4 d of culture. We successfully revived viable offspring from Hinai-dori, designated as a natural monument of Japan, from PGCs cryopreserved in these cryomedia. In conclusion, we developed two serum-free cryomedia that achieved > 60% recovery of viable PGCs after thawing while maintaining germline competency.
Malnutrition often suppresses reproductive function by inhibiting the pulsatile secretion of gonadotropin-releasing hormone (GnRH)/gonadotropins in mammals. This study aimed to determine whether cocaine- and amphetamine-regulated transcript (CART) neurons mediate the suppression of GnRH/gonadotropin pulses under malnutrition, since CART neurons have been reported to project to kisspeptin/neurokinin B/dynorphin A neurons (also known as the GnRH pulse generator) and GnRH neurons in rats. Wistar-Imamichi female rats were ovariectomized (OVX), and some of these rats were immediately implanted with subcutaneous Silastic tubing containing estradiol-17β (OVX + low E2) to maintain a diestrous level of estrogen. Free-moving conscious OVX and OVX + low E2 rats were subjected to 1-h frequent blood sampling followed by brain sampling to examine whether acute glucoprivation by peripheral administration of 2-deoxy-D-glucose (2DG), a glucose utilization inhibitor, suppressed the secretion of luteinizing hormone (LH) and activated hypothalamic CART neurons. The other cohort of animals was subjected to 3-h frequent blood sampling to examine whether central CART administration suppresses pulsatile LH secretion. Peripheral 2DG administration suppressed LH secretion and activated CART neurons in the hypothalamic supraoptic nucleus (SON) and parvocellular paraventricular nucleus (PVN), but not in the magnocellular PVN-zona incerta-dorsomedial nucleus continuum and arcuate nucleus, in OVX and OVX + low E2 rats. In addition, central CART administration suppressed pulsatile LH secretion in OVX and OVX + low E2 rats. These results suggest the possible involvement of CART neurons in the SON and parvocellular PVN in malnutrition-induced suppression of pulsatile LH secretion in female rats.
Artificial insemination (AI) is widely used in sheep breeding; however, fertility obtained with frozen-thawed ram semen following cervical (vaginal) insemination remains markedly low compared with fresh semen. This limitation contrasts with the high fertility achieved after laparoscopic intrauterine insemination, highlighting the central role of the ewe cervix as a selective barrier for frozen spermatozoa. This review examines current knowledge on the mechanisms underlying reduced fertility after cervical AI with frozen semen and proposes research avenues to improve reproductive outcomes. Despite cryotolerance of ovine sperm comparable to other ruminants, cryopreservation induces molecular and functional alterations that impair interactions with the female reproductive tract. While advances in semen freezing-such as antioxidant supplementation, lipid incorporation, and manipulation of seminal plasma-enhance post-thaw survival, they do not fully restore fertility, emphasizing the importance of female-side factors. Cervical morphology, uterine contractions, immune responses, and particularly cervical mucus properties influence sperm transport. Variations in mucin composition, glycosylation patterns, metabolite profiles, and microbiota composition are associated with breed-dependent differences in sperm survival and passage through the cervix. Emerging evidence suggests that targeted modulation of cervical mucus-potentially through dietary, oral, or local interventions-may represent a novel strategy to enhance fertility. Recent advances in imaging, 3D reconstruction, microfluidics, and organ-on-chip technologies provide unprecedented opportunities to model sperm-cervix interactions under physiologically relevant conditions. Integrating these tools with optimized cryopreservation strategies and a deeper understanding of cervical physiology is essential to overcome current barriers and improve the efficiency of cervical AI with frozen semen in sheep.
The variability observed in bull field fertility cannot be fully explained by conventional semen analysis. Work by our group and others has shown that ejaculates are highly heterogeneous and contain distinct sperm subpopulations (SSPs) that differ in motility, functionality, and susceptibility to processes such as cryopreservation, with recent evidence indicating differential interactions within the female reproductive tract (FRT). Therefore, these SSPs have the potential to influence sperm survival and the uterine and oviductal environments, which not only influence fertilization but also early embryo development success. This review discusses key sperm-related processes within the FRT, including molecular changes, penetration into the uterine glands, sperm reservoir formation, and, in particular, the role of the immune response and endometrial priming in fertility. Comparative studies between high- and low-fertility bulls offer valuable models for the investigation of the mechanisms behind fertility variation, providing indications of the relevance of some SSPs. By summarizing the existing knowledge on SSPs, this review aims to provide a framework for understanding sperm behavior within the FRT and highlights the need to better understand sperm heterogeneity and its role in successful pregnancy establishment.
Buffaloes are integral to the agricultural economies of numerous countries, providing essential contributions to milk and meat production, as well as draught power. Fertility in buffaloes is a complex quantitative trait that significantly affects both production and economic efficiency. Therefore, elucidating the genetic architecture underlying reproductive traits in buffaloes is critical for the development of sustainable breeding programs aimed at enhancing reproductive performance. This review provides an overview of the genetic basis of buffalo reproduction, summarizing recent advances in the estimation of genetic parameters for reproductive traits. It also consolidates information on genomic regions and candidate genes associated with reproductive traits, identified through genome-wide association studies (GWAS), selection signature analysis, and transcriptome profiling. Additionally, this review discusses the functional enrichment analysis and molecular networks among these candidate genes.
Mammalian spermatozoa begin swimming after ejaculation. After spermatozoa enter the oviduct, they undergo capacitation, penetrate the oocyte envelope, and fertilize the oocytes. These processes occur spontaneously but are influenced by hormones and neurotransmitters. Serotonin [5-hydroxytryptamine (5-HT)] is a well-known neurotransmitter found in reproductive organs. In the female reproductive system, serotonin is synthesized in the cumulus cells and affects steroidogenesis, oocyte maturation, fertilization, and embryo development. Recent studies have suggested that serotonin is also synthesized in spermatozoa and can affect motility, hyperactivation, acrosome reaction, and the success of in vitro fertilization (IVF) in hamsters, humans, mice, and rats. Importantly, the effects of serotonin on sperm function are dose-dependent, at least in hamsters, and serotonin concentrations in the female reproductive tract fluctuate during ovulation. The effects of serotonin on sperm function are mediated by 5-HT receptors (mainly 5-HT2 and 5-HT4), which stimulate Ca2+ and cyclic AMP signaling, respectively. The 5-HT2 receptor is involved in regulating motility and hyperactivation in hamsters, humans, and mice, whereas the 5-HT4 receptor is involved in regulating hyperactivation, the acrosome reaction, and IVF success in hamsters, mice, and rats. Because the 5-HT4 receptor is a common receptor in rodents associated with capacitation and IVF success and is stimulated by serotonin synthesized in spermatozoa, current evidence indicates that the 5-HT4 receptor is especially important for the regulation of rodent spermatozoal functions regulated by serotonin.
The female reproductive biology of the domestic dog is distinct from that of other mammalian species. Notably, female dogs ovulate immature oocytes that require a prolonged period within the oviduct to complete maturation. As a result, developing an effective in vitro oocyte maturation system for this species has proven challenging. Research efforts have focused on elucidating the mechanisms that regulate dog oocyte maturation. Current findings indicate that factors present in the follicular and oviductal environments play critical roles in the acquisition of developmental competence of dog oocytes. This review explores potential mechanisms regulating dog folliculogenesis and oogenesis and highlights the contributions of the ovarian and oviductal environments to the developmental competence of the gamete.
The beta-nerve growth factor (β-NGF), a seminal plasma protein with established luteotrophic effects in camelids and cattle, has been proposed as a modulator of periovulatory follicular function. The optimization of the steroidogenic environment of the preovulatory follicle is critical for oocyte maturation, corpus luteum formation, and embryo quality. However, the molecular actions of β-NGF on granulosa cells (GCs) during the periovulatory period in dairy heifers remain poorly defined. This study evaluated the effects of systemic administration of heterologous β-NGF (purified from llama seminal plasma) on the expression of steroidogenic enzymes in GCs from preovulatory follicles in estrus-synchronized Holstein heifers. Animals received 1 mg of β-NGF intramuscularly on Day 9 (estradiol benzoate administration) or Day 10 (fixed-time artificial insemination) of a progesterone(P4)/estradiol (E2)-based synchronization protocol. The follicular fluid and GCs were collected via transvaginal ultrasound-guided aspiration for hormone quantification and gene expression analysis. β-NGF treatment on Day 9 significantly upregulated Lutenizing hormone/choriogonadotropin receptor (LHCGR) and key steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase (HSD3B), Cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 17β-hydroxysteroid dehydrogenase (HSD17B), and Cytochrome P450 family 19 subfamily A member 1 (CYP19A1), whereas no transcriptional effects were observed when NGF was administered on Day 10, indicating a timing-dependent regulation of GCs differentiation. In contrast, Growth hormone receptor GHR and Steroidogenic acute regulatory protein expression levels remained unaffected, supporting the selectivity of NGF-induced transcriptional modulation. The follicular fluid P4/E2 ratios were not significantly altered by NGF treatment. These findings indicate that β-NGF increased steroidogenic and LHCGR gene abundance of GCs in a timing-dependent manner, suggesting that NGF may represent a potential modulator of the preovulatory follicle function in dairy cattle.
Seminal plasma is a pivotal regulator of reproductive success that contributes to fertility and fecundity beyond its traditionally recognized function as a vehicle for spermatozoa. Rich in soluble and extracellular vesicle-encased signaling molecules, seminal plasma influences sperm integrity and function, whilst simultaneously driving profound physiological changes in the female reproductive tract. These functions are broadly conserved across vertebrate and invertebrate species and help to optimize fertilization and create an immunological environment that supports implantation and fetal development. Perturbation of seminal plasma composition or ablation of its effects can affect fertility, the progression of pregnancy and even the long-term health of offspring. Given these far‑reaching effects, the responsiveness of seminal plasma composition to environmental exposures and influences has become an important focus of research. Studies across species using a variety of different physiological perturbations or environmental exposures have shown modification to the abundance and activities of soluble and extracellular vesicle-derived seminal plasma signaling molecules. Exposures to toxins, nutritional deficiency, metabolic disturbance, and infection-associated inflammation have each been shown to affect seminal plasma components with consequences for sperm function, female reproductive tract responses, embryo development, and offspring health. Collectively, these findings position seminal plasma, in addition to spermatozoa, as an important mediator of paternal environmental influences, offering a biological means through which males convey information on their physiological state to their mates and influence reproductive success across generations.