Dataset Information

Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility.

ABSTRACT: Multiple labs have reported that mammalian ovaries contain oogonial stem cells (OSCs), which can differentiate into oocytes that fertilize to produce offspring. However, the physiological relevance of these observations to adult ovarian function is unknown. Here we performed targeted and reversible ablation of premeiotic germ cells undergoing differentiation into oocytes in transgenic mice expressing the suicide gene, herpes simplex virus thymidine kinase (HSVtk), driven by the promoter of stimulated by retinoic acid gene 8 (Stra8), a germ cell-specific gene activated during meiotic commitment. Over a 21-day ablation phase induced by the HSVtk pro-drug, ganciclovir (GCV), oocyte numbers declined due to a disruption of new oocyte input. However, germ cell differentiation resumed after ceasing the ablation protocol, enabling complete regeneration of the oocyte pool. We next employed inducible lineage tracing to fate map, through Cre recombinase-mediated fluorescent reporter gene activation only in Stra8-expressing cells, newly-formed oocytes. Induction of the system during adulthood yielded a mosaic pool of unmarked (pre-existing) and marked (newly-formed) oocytes. Marked oocytes matured and fertilized to produce offspring, which grew normally to adulthood and transmitted the reporter to second-generation offspring. These findings establish that oocytes generated during adulthood contribute directly to ovarian function and natural fertility in mammals.

SUBMITTER: Wang N

PROVIDER: S-EPMC5577229 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility.

Wang Ning N Satirapod Chonthicha C Ohguchi Yasuyo Y Park Eun-Sil ES Woods Dori C DC Tilly Jonathan L JL

Scientific reports 20170830 1

Multiple labs have reported that mammalian ovaries contain oogonial stem cells (OSCs), which can differentiate into oocytes that fertilize to produce offspring. However, the physiological relevance of these observations to adult ovarian function is unknown. Here we performed targeted and reversible ablation of premeiotic germ cells undergoing differentiation into oocytes in transgenic mice expressing the suicide gene, herpes simplex virus thymidine kinase (HSVtk), driven by the promoter of stimu ...[more]

PMID: 28855574

Similar Datasets

Project description:BackgroundPremature ovarian insufficiency (POI) is a refractory disease that seriously affects the reproductive health of women and is increasing in incidence and prevalence globally. There is enormous demand to improve fertility in women with POI, while there is still lack of effective therapeutic methods in clinic. Cell-free fat extract (CEFFE) has been reported to contain thousands of active proteins which possess the ability to promote tissue repair in other diseases. In our study, we aimed to observe the efficacy and biosecurity of CEFFE on the repair of ovarian function and fertility of mice with POI and further explore the underlying mechanism.MethodsIn vivo, POI mice model, established by cyclophosphamide (CTX, 120 mg/kg) and busulfan (BUS, 12 mg/kg), was treated with CEFFE via the tail vein every two days for 2 weeks. Then, the weight of ovaries, estrous cycle and follicle count by H&E staining were measured. The content of AMH, E2 and FSH in serum was measured by Enzyme-linked immunosorbent assay. Fertility was evaluated by the number of oocytes retrieved, the development of embryos in vitro and the litter size. Biosecurity of parent mice and their pups were examined by body mass and visceral index. The proliferation and apoptosis of cells in ovaries were examined by immunohistochemistry and transmission electron microscopy. Furthermore, the mRNA-Seq of mouse ovarian granulosa cells was performed to explore underlying mechanism of CEFFE. In vitro, KGN cell line and human primary ovarian granulosa cells (hGCs) were treated with 250 μM CTX for 48 h with/without CEFFE. The proliferative ability of cells was detected by cell counting kit-8 assay (CCK-8) and EDU test; the apoptosis of cells was detected by TUNEL and flow cytometry.ResultsCEFFE recovered the content of AMH, E2 and FSH in serum, increased the number of follicles and the retrieved oocytes of POI mice (P < 0.05). CEFFE contributed to the development of embryos and improved the litter size of POI mice (P < 0.05). There was no side effect of CEFFE on parent mice and their pups. CEFFE contributed to the proliferation and inhibited the apoptosis of mouse granulosa cells in ovary, as well as in human ovarian granulosa cells (including KGN cell line and hGCs) (P < 0.05).ConclusionsThe treatment of CEFFE inhibited the apoptosis of granulosa cells and contributed to the recovery of ovarian function, as well as the fertility of mice with POI.

Dataset Information

Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility.

Publications

Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets