bims-ovagas 2026-03-29 papers

J Assist Reprod Genet. 2026 Mar 28.

Ovarian reserve testing: assessing oocyte quantity and quality.

David Frankfurter, Seth Barishansky, David B Seifer.

The oocyte provides the cellular architecture and molecular machinery for human development. Oocyte quality is closely tied to reproductive success; however, there is no consensus on how to measure it. As it stands, maternal age remains as the primary predictor of oocyte quality. Ovarian reserve, which conceptually reflects oocyte quantity and quality, is primarily assessed and expressed in terms of oocyte quantity. Ovarian reserve tests (ORT) serve as predictors of a patient's oocyte quantity and response to ovarian stimulation during in vitro fertilization (IVF). The question is not simply whether both oocyte quantity and quality decline with age-they do-but whether current ORTs, particularly anti-Müllerian hormone (AMH), can reliably predict both. An unresolved question is whether oocyte quality and quantity are inherently linked or are independent of one another. Oocyte quality has been described as a fertilized oocyte's ability to yield a live birth. With aging, oocyte aneuploidy rates increase and the likelihood of live birth declines. Yet, it remains unclear as to whether current markers of ovarian reserve can predict oocyte aneuploidy or IVF success. To gain deeper insight into the relationship between ORTs and reproductive potential requires a review of ovarian aging, contemporary ORT, and current evidence. Currently used ovarian reserve markers are reasonable predictors of relative oocyte quantity. AMH may also serve as a marker of egg quality. This review aims to provide a better understanding of the relationship between ovarian reserve tests, particularly AMH, and oocyte quantity and quality.

Keywords: Anti mullerian hormone; Diminished ovarian reserve; Follicle stimulating hormone; Ovarian reserve; Ovarian reserve testing; Pre-implantation genetic testing

DOI: https://doi.org/10.1007/s10815-026-03864-8

bioRxiv. 2026 Mar 03. pii: 2026.02.28.708733. [Epub ahead of print]

Macrophages regulate meiotic initiation and germ cell clearance in the developing ovary.

Xiaowei Gu, Satoko Matsuyama, Shu-Yun Li, Tony DeFalco.

Tissue-resident macrophages are increasingly recognized for their roles in promoting organogenesis, yet how macrophages are involved in fetal ovarian development remains unclear. In particular, little is known about ovarian macrophage ontogeny and how it relates to germ cell entry into meiosis and establishment of the oocyte reserve. Here we combine temporally-controlled lineage tracing of yolk-sac erythro-myeloid progenitors, fetal HSC-derived progenitors, and postnatal monocytes to map multi-wave seeding and remodeling of ovarian macrophages across fetal and early postnatal life. We identify three major resident subsets defined by MHCII and CSF1R that display distinct expansion kinetics and persistence, and we show that CCR2-dependent monocyte recruitment is required for efficient maturation of postnatal macrophage populations. Functionally, transient or sustained depletion of CSF1R+ fetal macrophages perturbs ovarian vascular growth and triggers precocious meiotic initiation without overt loss of germ cells, leading to persistent, premature meiotic progression. Extending macrophage depletion into late gestation disrupts perinatal physiological germ cell attrition despite rapid postnatal macrophage repopulation. Together, our findings establish ovarian macrophages as stage-specific regulators that couple immune ontogeny to ovarian morphogenesis and germ cell quality control during establishment of the oocyte reserve.

Keywords: germ cell; macrophage; macrophage ontogeny; meiotic initiation; monocyte; oocyte; oocyte reserve; ovarian development; ovarian follicle; ovary

DOI: https://doi.org/10.64898/2026.02.28.708733

MedScience. 2026 Mar 27.

Advances in multi-omics and aging clock research for female reproductive health and aging.

Rui Wang, Yaqian Li, Lan Zhu.

With the global increase in life expectancy, the aging of the female reproductive system has become a critical area of focus due to its profound implications for overall health and quality of life. Advances in multiomics technologies, encompassing epigenetics, transcriptomics, proteomics, metabolomics, and microbiomics, have provided transformative insights into the complex biology of female reproductive health and aging. Computational models called aging clocks, based on these approaches, enable the precise assessment of biological age, identification of tissue-specific vulnerabilities, and elucidation of systemic aging patterns. While multi-omics and aging clock research in the female reproductive tract remains an evolving field, the growing availability of high-quality studies and resources offers promising opportunities to advance our understanding of reproductive aging and other significant issues in female reproductive health, such as infertility and pregnancy complications.

Keywords: aging; aging clocks; female reproductive health; female reproductive tract; multi-omics

DOI: https://doi.org/10.1007/s11684-026-1207-1

J Reprod Immunol. 2026 Mar 18. pii: S0165-0378(26)00044-6. [Epub ahead of print]175 104875

Investigating autoimmunity in the etiology of premature ovarian insufficiency in a mouse model.

Nilay Kuscu, Ruth Appeltant, Sergej Petrovic, Suzannah A Williams.

Premature ovarian insufficiency (POI) is a major cause of infertility, yet its underlying mechanisms remain poorly understood. The double-mutant (DM) mouse, featuring oocyte-specific deletion of mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (Mgat1) and core 1 β-1,3-galactosyltransferase (C1galt1), develops early-onset POI and offers a valuable system to investigate causes. This study explored whether autoimmunity leads to POI in DM mice. We transplanted control and DM neonatal ovaries into immunocompromised hosts. Three months post-transplantation, follicular development was assessed. While both DM and control ovarian grafts contained follicles, only control ovaries showed healthy progression through to the antral stage. In contrast, DM ovaries exhibited a marked developmental block at the primary stage. In DM follicles, oocytes were smaller, and granulosa cell (GC) number and area were reduced at all follicular stages present. There was a strong correlation between oocyte growth and GC proliferation in controls, but was weaker in DM, suggesting disrupted oocyte-somatic cell communication. Analyses showed strong anti-Müllerian hormone (AMH) in Control GCs, whilst DM levels were less than half of the control, indicating compromised GC function in DM ovaries. Forkhead box L2 (FOXL2) was also reduced in DM follicles compared to control GCs. The persistence of follicular defects, including reduced AMH and FOXL2 levels, in DM ovaries even in severe combined immunodeficient mice reveals that POI is not due to autoimmunity and the phenotype results from intrinsic defects in follicular development caused by the oocyte-specific mutation. These findings underscore the role of oocyte-GC interactions in follicle development and contribute to our understanding of POI pathogenesis.

Keywords: Autoimmunity; Follicle development; Ovary; Premature ovarian insufficiency

DOI: https://doi.org/10.1016/j.jri.2026.104875

Hum Reprod. 2026 Mar 24. pii: deag053. [Epub ahead of print]

The World Health Organization infertility guidelines: "Presumption of ovulation".

Mohan S Kamath.

Keywords: female infertility; follicle development; ovarian function; ovulation; polycystic ovaries; progesterone

DOI: https://doi.org/10.1093/humrep/deag053

Hum Reprod. 2026 Mar 26. pii: deag051. [Epub ahead of print]

Spatial transcriptomics in the human adult ovary: insights into key signalling pathways during follicular atresia.

Hanne Vlieghe, Fu Wei, Hui Cheng, Tessa H R Stolk, Judith A Huirne, Norah M van Mello, Christiani A Amorim, Susana M Chuva de Sousa Lopes.

STUDY QUESTION: Are key signalling pathways WNT, TGFβ/BMP, NOTCH, and HH involved in follicular atresia in the human adult ovary?
SUMMARY ANSWER: In this study, we used spatial transcriptomics to investigate the progression of follicular atresia, focusing on genes of interest associated with steroidogenesis and key signalling pathways WNT, TGFβ/BMP, NOTCH, and HH.
WHAT IS KNOWN ALREADY: While extensive research has focused on the mechanisms driving follicular growth, much less is known about the process of follicular atresia, despite its relevance for ovarian aging and reproductive longevity. Follicular atresia is characterized by complex molecular and cellular changes, that lead to the degeneration of granulosa and theca cells.
STUDY DESIGN, SIZE, DURATION: Spatial transcriptomics was conducted on 16 regions of human ovarian tissue from different donors (N = 6) containing 21 small antral follicles (diameter 0.5-4 mm) healthy and at different stages of atresia.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We selected 80 genes to facilitate cell type identification in the ovary and to investigate the key signalling pathways WNT, TGFβ/BMP, NOTCH, and HH. Haematoxylin and eosin staining was used to manually select different follicle types for spatial transcriptomics. The Molecular Cartography platform (Resolve BioSciences) multiplexing single-molecule fluorescence in situ hybridization on cryo-sections was used for spatial transcriptomics. The cell segmentation masks were obtained from Resolve BioSciences and transcripts for each gene were assigned to individual cells based on the segmentation mask. Downstream visualization and quantification were performed using AnnData and Python.
MAIN RESULTS AND THE ROLE OF CHANCE: By comparing the molecular signature of cell types present in healthy small antral follicles to those observed during the progression of atresia, we revealed a profound cellular and molecular shift. Key signalling pathways exhibited a general downregulation in granulosa cells, whereas expression in internal theca cells increased transiently at the onset of atresia, in line with ongoing cellular degeneration and follicular remodelling.
LARGE SCALE DATA: N/A.
LIMITATIONS, REASONS FOR CAUTION: This study was conducted on ovarian tissue from transmasculine donors. We cannot exclude that testosterone therapy impacts follicular dynamics.
WIDER IMPLICATIONS OF THE FINDINGS: Our study provides novel insights into the spatial and molecular mechanisms of follicular atresia, contributing to a deeper understanding of the ovarian biology in humans.
STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Fonds National de la Recherche Scientifique de Belgique (T.0004.20 to H.V. and C.A.A.), the Novo Nordisk Foundation (NNF21CC0073729, reNEW to F.W., H.C., and S.M.C.S.L.), the Dutch Organization for Health Research and Development (ZonMW PSIDER-2021-10250022120001 to S.M.C.S.L.), and the China Scholarship Council (CSC 202008450034 to F.W., CSC 202008320362 to H.C.). The authors have no conflicts of interest to declare.

Keywords: adult; follicular atresia; folliculogenesis; human; ovary; signalling pathways; spatial transcriptomics; steroidogenesis

DOI: https://doi.org/10.1093/humrep/deag051