# BDNF Promotes In Vitro Maturation of Sheep Oocytes by Alleviating Oxidative Stress and Endoplasmic Reticulum Stress

**Authors:** Ning Zhang, Yukun Song, Xitong Han, Nan Zhang, Jiaxin Zhang

PMC · DOI: 10.3390/antiox15020234 · Antioxidants · 2026-02-11

## TL;DR

Adding BDNF during sheep oocyte maturation reduces stress and improves embryo development.

## Contribution

Demonstrates BDNF's novel role in reducing oxidative and endoplasmic reticulum stress during sheep oocyte maturation.

## Key findings

- BDNF improved oocyte maturation by reducing ROS and endoplasmic reticulum stress.
- BDNF increased mitochondrial membrane potential and blastocyst formation rates.
- BDNF enhanced transzonal projections and gap junctions during maturation.

## Abstract

In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress response in oocytes, ultimately reducing the developmental potential of early embryos. Brain-derived neurotrophic factor (BDNF) is an ovarian endocrine factor that can enhance the function of follicular granulosa cells and promote oocyte maturation, but the specific pathways remain unclear. We supplemented IVM cultures of sheep oocytes with BDNF and examined aspects of oocyte nuclear and cytoplasmic maturation. The addition of 50 ng/mL BDNF promoted the expansion of cumulus cells and increased the rates of first polar body extrusion, cleavage, and blastocyst formation. Compared with untreated controls, BDNF-treated oocytes had improved Ca2+ homeostasis, enhanced expression of antioxidant genes, decreased ROS levels and expression of endoplasmic reticulum stress genes, and increased mitochondrial membrane potential, mitochondrial biogenesis, and numbers of cells with proper distributions of mitochondria and endoplasmic reticulum. Further analysis indicated that BDNF affected oocyte maturation by increasing the numbers of transzonal projections and gap junctions during the IVM process. In summary, the addition of BDNF during the IVM process improved sheep oocyte maturation and embryo development by reducing oxidative stress and endoplasmic reticulum stress. These findings deepen our understanding of the regulatory mechanisms of BDNF during IVM and provide experimental data to improve in vitro embryo production from sheep oocytes.

## Linked entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627]
- **Chemicals:** Ca2+ (PubChem CID 271)

## Full-text entities

- **Genes:** HAS2 [NCBI Gene 101110341], GJA1 (gap junction protein alpha 1) [NCBI Gene 2697] {aka AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL}, VCAN [NCBI Gene 100294605], SOD2 [NCBI Gene 780457], TNFAIP6 [NCBI Gene 101119185], GAPDH [NCBI Gene 443005], CREB [NCBI Gene 443118], GPX1 [NCBI Gene 100820742], NTRK2 [NCBI Gene 101116015], DUSP1 [NCBI Gene 101107632], ATF6 [NCBI Gene 541606], PRDX1 [NCBI Gene 101120966], PTGS2 [NCBI Gene 443460], NADH dehydrogenase subunit 5 [NCBI Gene 808258], BCL2 [NCBI Gene 101119602], BDNF [NCBI Gene 101117275], Caspase3 [NCBI Gene 443031], PTX3 [NCBI Gene 100034672], BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, CAT [NCBI Gene 100307035], Caspase9 [NCBI Gene 101110953], GJA4 (gap junction protein alpha 4) [NCBI Gene 2701] {aka CX37}, beta-actin [NCBI Gene 100885765]
- **Diseases:** development (MESH:D002658), ERS (MESH:D000079225), viral infection (MESH:D014777), polycystic ovary syndrome (MESH:D011085), hypoxia (MESH:D000860), inflammatory (MESH:D007249), injury to (MESH:D014947), premature ovarian insufficiency (MESH:D016649), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** heparin (MESH:D006493), LH (MESH:D007986), PBS (MESH:D007854), ROS (MESH:D017382), Calcium (MESH:D002118), CO2 (MESH:D002245), GSH (MESH:D005978), ATP (MESH:D000255), Rhodamine Phalloidin (MESH:C504731), Fluo-3 AM (MESH:C059715), paraformaldehyde (MESH:C003043), cysteine (MESH:D003545), lipid (MESH:D008055), Hoechst 33342 (MESH:C017807), TB Green (-), penicillin (MESH:D010406), JC-1 (MESH:C068624), essential amino acids (MESH:D000601), DCFH-DA (MESH:C029569), N2 (MESH:D009584), 17beta-estradiol (MESH:D004958), mineral oil (MESH:D008899), K252a (MESH:C049985), streptomycin (MESH:D013307), Rhod-2 AM (MESH:C068483), PVA (MESH:C063253), Triton X-100 (MESH:D017830), O2 (MESH:D010100)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Suidae (boars, family) [taxon 9821], Homo sapiens (human, species) [taxon 9606], Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** S1061M, S0033S

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12938486/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938486/full.md

## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938486/full.md

---
Source: https://tomesphere.com/paper/PMC12938486