DISCUSSION

Reproductive impact of FMD under field conditions

FMD is a highly contagious viral disease that spreads rapidly and remains a major challenge in many countries, including Indonesia, where the disease re-emerged in 2022 [35]. The incidence of FMD in Indonesia, particularly in Java during 2022–2023, reportedly reached 308,148 cases across multiple species, with 96.4% in cattle [36]. This situation contributed to reduced cattle populations, decreased milk production, increased livestock mortality [20], and higher rates of early embryonic loss [7]. Oktanella et al. [21] also reported decreased milk production following the outbreak. Consequently, mass vaccination has become the primary strategy for limiting transmission in susceptible cattle populations [37].

However, scientific evidence on the effects of FMD infection and vaccination on bovine fertility remains limited, although fertility is an important indicator of longer-term economic losses that may not be immediately apparent. Because reproductive performance is influenced by environmental and management factors, a robust evaluation requires before-and-after comparisons following exposure to the outbreak [38, 39]. In this study, a retrospective within-animal before-and-after approach was used to compare reproductive performance in HF heifers before-and-after natural FMD infection or vaccination. To the best of our knowledge, this is the first study to use this design to directly compare the reproductive consequences of natural FMD infection and vaccination in dairy heifers. It also represents one of the first detailed field-based assessments of reproductive performance following the 2022 re-emergence of FMD in Indonesia, after more than three decades free from the disease. Although this study was not designed to compare reproductive outcomes among different FMDV lineages, it provides field-based evidence of reproductive impairment following the 2022 Indonesian outbreak associated with the O/ME-SA/Ind-2001e lineage.

Effects of natural FMD infection on fertility

Heifers directly infected with FMD (Condition 1) showed marked reductions in reproductive performance after exposure, reflected by significantly lower FSCR and PR. This decline was plausibly related to reduced feed intake during the early phase of infection, due to painful lesions on the lips and tongue [3]. Nutritional deficiency can impair ovarian and uterine function, thereby compromising embryo development and implantation [40]. In addition, the decline in PR may reflect the more persistent adverse effects of FMD in cattle than in other species, where these effects are often more transient [41].

In cattle, FMD infection has been associated with heat intolerance syndrome, respiratory distress, and reproductive disorders that may persist after apparent clinical recovery, with residual effects reported for years after major outbreaks [10, 42]. The reduced reproductive performance observed after natural FMD infection is unlikely to be attributable to generalized immunosuppression. Experimental studies have shown that cattle remain immunocompetent during the acute phase of FMDV infection, maintaining stable leukocyte counts and intact T-cell responses, with only minimal systemic cytokine dysregulation [43]. Therefore, reproductive impairment in Condition 1 is more plausibly explained by indirect physiological effects of infection, particularly disruption of energy metabolism, which may subsequently reduce fertility [44]. Although reproductive hormones were not directly measured in this study, prior evidence suggests that FMDV infection may disrupt reproductive endocrine function [45]. This decline in fertility after natural FMD infection is consistent with previous evidence from Indonesia, as Syah et al. [7] reported changes in AI success rates in HF cows following the FMD outbreak in the same province.

Effects of FMD vaccination on fertility

Vaccination is a key strategy for protecting susceptible cattle populations against FMD transmission and mitigating the broader reproductive impacts of the disease. However, its effectiveness should also be evaluated in relation to reproductive performance [46]. Findings from Conditions 2 and 3 suggest that vaccination in heifers did not consistently produce marked adverse reproductive effects. In Condition 2, FSCR and PR did not differ significantly before-and-after vaccination, although PR was slightly lower after vaccination (p = 1.00 for FSCR and p = 0.57 for PR). In Condition 3, FSCR was not significantly altered (p = 0.72), whereas PR showed a modest but statistically significant decline after vaccination (p = 0.04). Importantly, the magnitude of this decline was smaller than that observed in heifers directly affected by natural FMD infection.

This difference is biologically plausible. Vaccination delivers a controlled dose of inactivated antigen [47], thereby limiting excessive immune activation and tissue damage [48, 49]. After vaccination with an inactivated FMDV vaccine, the immune system is primarily activated by the adjuvant and non-replicating viral antigens. This stimulation induces a controlled and localized innate immune response, resulting in mild systemic inflammation, such as transient fever and lethargy, and short-term physiological stress that typically resolves rapidly [50–52]. Unlike natural infection, vaccination induces a controlled immune response without viral replication, thereby avoiding the prolonged physiological stress associated with acute disease. This interpretation aligns with evidence that cattle do not experience immunosuppression during FMDV exposure [43], supporting the view that vaccination-related reproductive effects are transient and largely mediated by short-term inflammatory and metabolic adjustments rather than by immune dysfunction.

Timing of AI after FMD infection or vaccination

In addition to the main before-and-after comparison, an exploratory analysis evaluated whether the interval between FMD infection or vaccination and the first post-exposure AI was associated with first-service conception outcomes. Table 3 showed a consistent pattern across all three conditions, in which first AI performed >90 days after FMD infection or vaccination was associated with the most favorable reproductive performance. Although a similar numerical trend was observed in Condition 2, the differences were not statistically significant, dulikely toe of the limited sample size and the sparse number of conception events in this group.

These findings are consistent with Garcia-Pintos et al. [53], who showed that FMD vaccination administered close to breeding or early pregnancy was associated with a higher likelihood of pregnancy failure. Together, these results suggest that the early post-infection or post-vaccination period may represent a vulnerable reproductive window, during which residual inflammatory, febrile, metabolic, or endocrine disturbances may compromise fertilization, early embryonic development, or pregnancy establishment.

Conception interval and reproductive efficiency

The findings on the conception interval further support these interpretations. Heifers in Condition 1 showed delayed conception after exposure, indicating that the adverse reproductive effect of natural FMD extended beyond the first insemination and reduced overall reproductive efficiency during follow-up. Descriptively, S/C also tended to increase after exposure across all conditions, which was broadly consistent with the pattern of reduced fertility. However, because S/C was evaluated descriptively rather than inferentially, this finding should be interpreted cautiously.

Reproductive record exit after FMD exposure

Reproductive record exit after FMD infection or vaccination was also assessed. Because all animals were survivors and follow-up focused on the post-exposure reproductive period, this outcome should be interpreted as a proxy measure of reproductive record exit rather than a confirmed culling endpoint attributable solely to reproductive failure. The highest proportion of removals during the 180-day observation period was observed among heifers that experienced clinical FMD during the outbreak (Condition 1). However, the between-condition comparison was more complex than suggested by crude proportions alone because the hazard of removal varied over time.

In particular, the removal pattern in Condition 3 was time-dependent, with distinct risk profiles in the early and late post-exposure periods. This finding indicates that herd removal after vaccination or outbreak exposure cannot be interpreted exclusively as a direct reflection of fertility status. Rather, it likely also reflects management decisions made under outbreak conditions, including concerns regarding infection risk, economic pressure, herd restructuring, or precautionary removal of animals perceived to be at higher epidemiological risk [54, 55].

Overall implications

Overall, these results indicate that natural FMD infection had a substantially greater detrimental effect on reproductive performance in HF heifers than FMD vaccination, as reflected by clearer declines in conception outcomes and delayed pregnancy establishment. Although both naturally infected and vaccinated heifers showed reductions in FSCR and PR, these declines were 23% lower for FSCR and 26% lower for PR in vaccinated heifers. Given that FMD is among the most economically devastating livestock diseases, the overall benefits of vaccination for animal health, outbreak control, and economic protection likely outweigh the relatively limited reproductive effects observed after vaccination [53]. Therefore, vaccination programs remain essential for protecting cattle populations against infection and mitigating the broader reproductive consequences of FMD under field conditions.

Limitations

Several limitations should be considered. First, the retrospective design relied on cooperative reproductive records, and several potentially important confounders, such as body weight, body condition score, semen batch quality, and AI technician identity, were not consistently available. Nutritional status, previous health history, farm-level management practices, and indicators of energy balance, including non-esterified fatty acids and β-hydroxybutyrate, were also inconsistently recorded and could not be fully adjusted for in the statistical analyses. Although the within-animal before-and-after design reduced some between-animal variability, residual confounding may have influenced the observed associations among FMD exposure, vaccination, and reproductive outcomes.

Second, reproductive record exit was based on a proxy definition because complete farm-level records of culling, sale, transfer, and mortality were unavailable. Therefore, this outcome should not be interpreted as confirmed culling because of infertility. Some heifers may have been sold, transferred to other farms, or lost from reproductive recording. Accordingly, reproductive record exit was interpreted as an exploratory outcome and was de-emphasized relative to the main fertility outcomes.

Third, the study was conducted within a single dairy cooperative, which may restrict the generalizability of the findings to other dairy production systems. However, the relatively large sample size (n = 772) and the use of real-world smallholder field data enhance the external validity of the results for comparable dairy production systems in Southeast Asia and other developing tropical regions.