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Updated: Feb 23, 2026
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility
Ning Wang1,2, Chonthicha Satirapod1,2, Yasuyo Ohguchi1,2
1Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA.
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.
Insights
Mammalian ovaries regenerate oocytes from stem cells, even in adulthood. These newly formed oocytes contribute to fertility and offspring, confirming their physiological relevance in adult ovarian function.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Genetics
Background:
- Mammalian ovaries are thought to have a finite oocyte pool established before birth.
- The existence and function of oogonial stem cells (OSCs) in adult ovaries remain debated.
- Previous studies suggested the presence of OSCs, but their physiological relevance to adult ovarian function was unclear.
Purpose of the Study:
- To investigate the functional contribution of newly generated oocytes in adult mammalian ovaries.
- To determine if oocytes formed postnatally can support natural fertility.
- To clarify the role of oogonial stem cells in maintaining ovarian function throughout reproductive life.
Main Methods:
- Used transgenic mice with a suicide gene (HSVtk) under the control of a germ cell-specific promoter (Stra8) for targeted ablation of differentiating germ cells.
- Administered ganciclovir (GCV) to induce reversible ablation of oocyte precursors.
- Employed inducible lineage tracing (Cre-lox system) to mark newly formed oocytes in adult mice.
- Assessed oocyte regeneration, maturation, fertilization, and offspring viability.
Main Results:
- Targeted ablation of differentiating germ cells temporarily reduced oocyte numbers but allowed for complete regeneration of the oocyte pool after cessation of the treatment.
- Inducible lineage tracing confirmed the generation of new oocytes in adult mice.
- These newly formed oocytes were capable of maturation, fertilization, and producing viable offspring that were fertile and transmitted the genetic marker to subsequent generations.
Conclusions:
- Oocytes generated during adulthood contribute directly to the ovarian reserve and natural fertility in mammals.
- The study provides strong evidence for the physiological relevance and functionality of oogonial stem cells in adult ovaries.
- Mammalian ovaries possess a regenerative capacity for oocyte production throughout reproductive lifespan.
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