What this means
5% of adults worldwide. Mitochondria are central to oocyte developmental competence, and a novel class of mitochondrial genome-encoded peptides, mitochondrial-derived peptides(MDPs) comprising MOTS-c, Humanin and small Humanin-like peptide2(SHLP2), regulates cellular metabolism, oxidative stress and apoptosis.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Earlier studies
- Kind of research
- A summary of earlier studies
The science
- Original title
- Mitochondrial-derived peptides in female reproduction: Emerging regulators of oocyte competence and novel therapeutic opportunities for infertility.
- Authors
- Rostami Z, Galeshi M, Mosapour A
- Journal
- Tissue & cell
- Published
- Oct 15, 2026
- Study type
- Review
- PMID
- 42880137 ↗
Abstract
Female infertility affects approximately 17.5% of adults worldwide. Mitochondria are central to oocyte developmental competence, and a novel class of mitochondrial genome-encoded peptides, mitochondrial-derived peptides(MDPs) comprising MOTS-c, Humanin and small Humanin-like peptide2(SHLP2), regulates cellular metabolism, oxidative stress and apoptosis. This hypothesis-driven perspective aims to:(i) synthesize indirect evidence to construct a mechanistic framework for MDP involvement in oocyte physiology and female infertility;(ii) propose prioritized research questions; and(iii) delineate translational paths toward MDP-based biomarkers and therapeutics in assisted reproductive technology(ART). PubMed, Scopus and Web of Science were searched up to May 2025 using terms related to MDPs, oocytes, follicular fluid, ovarian aging and IVF. Bibliographies were hand-searched. The search yielded 312 records, of which 87 were retained. The three principal MDPs decline with age in humans, mirroring the age-related deterioration of oocyte quality. The reduced MOTS-c in polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome, PCOS) (a 56% reduction in serum concentration versus controls, P < 0.001), provides preliminary evidence, albeit unreplicated and without ovarian sampling. Mechanistically, MDPs activate AMPK(MOTS-c), sequester pro-apoptotic Bax(Humanin), and reduce mitochondrial ROS while enhancing electron transport chain activity(SHLP2). Humanin is already known to be present in human follicular fluid and to associate with ovarian reserve and PMOS-related insulin resistance; we propose that this extends to MOTS-c and SHLP2, that composite MDP levels correlate with oocyte-specific quality parameters, and that a composite biomarker panel could improve IVF outcome prediction beyond AMH alone. MDPs(MOTS-c,Humanin,SHLP2) decline with age, regulate AMPK, suppress oxidative stress and inhibit apoptosis; processes that drive oocyte quality decline. Reduced MOTS-c in PMOS provides an initial, unreplicated clinical link. Convergent biology positions MDPs as promising candidates to improve IVF outcomes. Direct empirical testing, starting with quantification of MDPs in human follicular fluid and granulosa cells, is now warranted.
Rostami Z, Galeshi M, Mosapour A Mitochondrial-derived peptides in female reproduction: Emerging regulators of oocyte competence and novel therapeutic opportunities for infertility. Tissue & cell. 2026. doi:10.1016/j.tice.2026.104044. PMID: 42880137. https://pubmed.ncbi.nlm.nih.gov/42880137/
Related research
Humanin treatment eased heart damage in diabetic mice
Mice with diabetes that got daily humanin for 15 days had less stress, inflammation, and cell death in the heart. This was tested in mice only, so it does not show the same would happen in people.
Humanin protein family may help steer cell stress responses
Researchers mapped how Humanin-related proteins connect to other proteins in a computer network. They suggest these proteins may guide stress responses, not just act alone. This is a model, so it does not show these proteins work this way in people.
Humanin, a small mitochondrial peptide, protected ovary cells from oxidative damage in lab tests
Researchers found that humanin helped human ovary cells and rat ovary tissue survive damage from oxidative stress. This was tested in cells and tissue, not people, so it does not show effects in humans.
AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition.
Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction.
A humanin analog eased kidney damage in diabetic mice and cells
Researchers found a treated protein reduced kidney damage and cell death in diabetic mice. This work was in mice and cells, so it does not show the same effect in people.
Emerging regulators of human physiology and disease; sORF-encoded microproteins.
The human genome contains hundreds of thousands of short open reading frames (sORFs), yet their translational products, hereafter referred to as sORF-encoded microproteins (also historically termed micropeptides), have…