# Genetic and Environmental Architecture of Ram Fertility Traits: A Review

**Authors:** Kaiyue Zheng, Krishani Sinhalage, Guilherme Henrique Gebim Polizel, Ángela Cánovas

PMC · DOI: 10.3390/genes17020210 · Genes · 2026-02-09

## TL;DR

This review explores genetic and environmental factors affecting ram fertility, highlighting key genes and management strategies to improve sheep reproduction.

## Contribution

The paper identifies novel genetic markers and environmental interactions influencing ram fertility through synthesis of genomic and transcriptomic studies.

## Key findings

- Candidate genes like SLC2A8 and MAPK3 are linked to spermatogenesis and semen quality in rams.
- Y-linked SNPs such as ZFY16: g.146 C > T are associated with testicular development.
- Heat stress disrupts testicular thermoregulation, affecting spermatogenesis even in adapted breeds.

## Abstract

Background/Objectives: Ram fertility is essential for sheep production, influenced by genetic, physiological, behavioral, and environmental factors. This narrative review synthesizes findings from over 190 peer-reviewed publications to evaluate the phenotypic indicators, genetic architecture, molecular candidates, and management conditions influencing testicular development, semen quality, and reproductive performance in rams. Methods: A narrative synthesis of peer-reviewed studies was conducted, integrating findings from quantitative genetics, genome-wide association studies, transcriptomics, and controlled environmental and management experiments. Emphasis was placed on studies evaluating fertility-related traits across breeds, ages, and production systems. Results: Recent genomic and transcriptomic studies have identified potential biomarkers (e.g., IGF1, IGFALS, FOXO1) and gene networks linked to ram fertility, including semen quality, scrotal circumference, and endocrine regulation. For instance, genome-wide association studies (GWASs) have identified candidate genes such as SLC2A8 and MAPK3, which are associated with spermatogenesis and semen quality. Additionally, Y-linked SNPs such as ZFY16: g.146 C > T have been linked to testicular development. Genetic potential is heavily modulated by environmental constraints. Heat stress emerges as a disruptor of testicular thermoregulation, with recent evidence highlighting the vulnerability of spermatogenesis even in adapted breeds. Management interventions, specifically nutritional supplementation and hormonal modulation via melatonin, are discussed as effective strategies to mitigate environmental impacts. Conclusion: Improving ram fertility will require an approach that prioritizes phenotypic traits supported by candidate genes identified through transcriptomic analyses and GWASs. Integrating these genetic tools together with cost-effective nutritional and hormonal management strategies can further improve semen quality, libido, and testicular traits, thereby enhancing fertility gains while maintaining sheep breed adaptability across production systems.

## Linked entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479], IGFALS (insulin like growth factor binding protein acid labile subunit) [NCBI Gene 3483], FOXO1 (forkhead box O1) [NCBI Gene 2308], SLC2A8 (solute carrier family 2 member 8) [NCBI Gene 29988], MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595], ZFYVE16 (zinc finger FYVE-type containing 16) [NCBI Gene 122918119]

## Full-text entities

- **Genes:** KRT4 [NCBI Gene 101108902], ALDOA [NCBI Gene 443085], LH-R [NCBI Gene 101113228], PDYN [NCBI Gene 100294654], DDB1 [NCBI Gene 101106122], NOTCH2 [NCBI Gene 101112098], SOD2 [NCBI Gene 780457], CDK1 [NCBI Gene 100216432], IVL [NCBI Gene 101123427], TTC12 [NCBI Gene 101109209], PADI2 [NCBI Gene 101108464], FSH-beta [NCBI Gene 443387], FOXO1 [NCBI Gene 101107877], HMOX1 [NCBI Gene 101120910], KISS1 [NCBI Gene 101107719], LOC106991431 [NCBI Gene 106991431], GDF9 [NCBI Gene 100217402], GADD45A [NCBI Gene 101115240], FAM126B [NCBI Gene 101106405], SH2B1 [NCBI Gene 101112187], BMP2 [NCBI Gene 443173], LOC105609364 [NCBI Gene 105609364], LMBR1 [NCBI Gene 101117926], NOM1 [NCBI Gene 101118183], Growth Hormone [NCBI Gene 443329], RAB3B [NCBI Gene 101112608], RGS2 [NCBI Gene 443163], GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, LH-beta [NCBI Gene 443395], CCT4 [NCBI Gene 101119712], Smad5 [NCBI Gene 443172], CCDC39 [NCBI Gene 101105124], LAMB3 [NCBI Gene 101105176], INH-betaB [NCBI Gene 101119286], AK1 [NCBI Gene 100302085], RASIP1 [NCBI Gene 101107986], GNRHR [NCBI Gene 443413], Smad9 [NCBI Gene 101105084], EPHA7 [NCBI Gene 101107288], IGFALS [NCBI Gene 101111599], ROPN1 [NCBI Gene 101116109], GABRD [NCBI Gene 101122539], TEKT3 [NCBI Gene 101115807], GnRH [NCBI Gene 443529], MTNR1A [NCBI Gene 443022], TNP1 [NCBI Gene 101108026], MKLN1 [NCBI Gene 101119131], LEP [NCBI Gene 443534], AVP [NCBI Gene 443477], INH-alpha [NCBI Gene 101118082], SLC2A8 [NCBI Gene 443166], MCHR1 [NCBI Gene 101108822], SEPTIN2 [NCBI Gene 101123521], SYCP2 [NCBI Gene 101123486], NFKBIL1 [NCBI Gene 101104353], TSHB [NCBI Gene 101104284], SYCP3 [NCBI Gene 101108560], Akt [NCBI Gene 100294652], TAF9B [NCBI Gene 101117906], ITCH [NCBI Gene 101118041]
- **Diseases:** Infectious agents (MESH:D003141), oligospermia (MESH:D009845), parasitic infections (MESH:D010272), Fertility (MESH:D007246), infection (MESH:D007239), embryonic loss (MESH:D020964), azoospermia (MESH:D053713), Viral infections (MESH:D014777), undernutrition (MESH:D044342), hyperthermia (MESH:D005334), junctional epidermolysis bullosa (MESH:D016109), sperm abnormalities (MESH:C567467), head and acrosome abnormalities (MESH:D006258), fibrosis (MESH:D005355), injury to (MESH:D014947), epididymal inflammation (MESH:D007249), epididymitis (MESH:D004823), developmental abnormalities (MESH:D006130), hereditary disorders (MESH:D009386)
- **Chemicals:** LH (MESH:D007986), eosin (MESH:D004801), calcium (MESH:D002118), folic acid (MESH:D005492), ROS (MESH:D017382), glucose (MESH:D005947), Mn (MESH:D008345), Co (MESH:D003035), steroid hormone (MESH:D013256), ATP (MESH:D000255), I (MESH:D007455), Cloprostenol (MESH:D003008), amino acid (MESH:D000596), nigrosin (MESH:C002712), Se (MESH:D012643), malondialdehyde (MESH:D008315), Melatonin (MESH:D008550), SC (-), oxytocin (MESH:D010121), progesterone (MESH:D011374), Cu (MESH:D003300), L-citrulline (MESH:D002956), PGF2alpha (MESH:D015237), ketone body (MESH:D007657), vitamin A (MESH:D014801), Fe (MESH:D007501), testosterone (MESH:D013739), cortisol (MESH:D006854), PGs (MESH:D011453), adrenal (MESH:D004837), T (MESH:D014316), pyruvate (MESH:D019289), Zn (MESH:D015032), oxygen (MESH:D010100), FSH (MESH:D005640)
- **Species:** Capra hircus (domestic goat, species) [taxon 9925], Rattus norvegicus (brown rat, species) [taxon 10116], Actinobacillus seminis (species) [taxon 722], Homo sapiens (human, species) [taxon 9606], Mivirus boleense (species) [taxon 2845619], Brucella ovis (species) [taxon 236], Histophilus somni (species) [taxon 731], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090], Withania somnifera (ashwagandha, species) [taxon 126910], Pelophylax esculentus [taxon 8401]
- **Mutations:** g.170 G > A, c.3631C > G, g.146 C > T, g.332 G > A, c.937A > G, g.146 C > T, g.77 C > G, A113G, C893A

## Full text

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## Figures

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## References

198 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940677/full.md

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Source: https://tomesphere.com/paper/PMC12940677