Single-cell and spatiotemporal profile of ovulation in the mouse ovary
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ABSTRACT:
PROVIDER: PRJNA1250453 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33132538.fastq.gz | Fastqsanger.gz | |||
| SRR33132539.fastq.gz | Fastqsanger.gz | |||
| SRR33132540.fastq.gz | Fastqsanger.gz | |||
| SRR33132541.fastq.gz | Fastqsanger.gz | |||
| SRR33132542.fastq.gz | Fastqsanger.gz |
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Project description:Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.
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Project description:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. The disturbance of ovarian immune microenvironment contributes to the disorders of follicle development and ovulation, and the mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with the oocyte fertilization rate and the high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells, indicating that IL-22 acted through IL-22R1 and STAT3 signalling pathway to promote follicle development and ovulation in PCOS. In summary, this study elucidated the vital role of ovarian immune microenvironment in follicle development and ovulation, the application of IL-22 may provide new insights into the treatment of PCOS patients.
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Project description:Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2) in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here we show that the PGR plays an additional essential role; attenuate ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the NF-κB, a transcription factor required for Ptgs2 expression. When the expression of PGR was ablated in the granulosa cells, the ovary undergoes hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. Despite the ovary undergoes ovulations dozens or hundreds of times in one’s lifetime, the repetitive ovulatory inflammations do not leave significant tissue damage in the ovary. The PGR-driven termination of PTGS2 expression may protect ovary from the ovulatory inflammation.
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Project description:Unraveling the composition and regulation of the oviduct fluid (OF) is crucial to understand the microenvironment in which sperm capacitation, fertilization and early embryo development take place. Therefore, our aim was to determine the spatiotemporal changes in the OF proteome according to the anatomical region of the oviduct (ampulla vs. isthmus), the proximity of the ovulating ovary (ipsilateral vs. contralateral side) and the peri-ovulatory stage (pre-ovulatory or Pre-ov vs. post-ovulatory or Post-ov). Oviducts from adult cyclic cows were collected at a local slaughterhouse and pools of OF were analyzed by nanoLC-MS/MS and label-free protein quantification (n=32 OF pools for all region stage side conditions). A total of 3,760 proteins were identified in the OF, of which 37% were predicted to be secreted. The oviduct region was the major source of variation in protein abundance, followed by the proximity of the ovulating ovary and finally the peri-ovulatory stage. Differentially abundant proteins between regions, stages and sides were involved in a broad variety of biological functions, including protein binding, response to stress, cell-to-cell adhesion, calcium homeostasis and the immune system. This work highlights the dynamic regulation of oviduct secretions and provides new protein candidates for interactions between the maternal environment, the gametes and the early embryo.
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