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Ovulation defect and its restoration by bone marrow transplantation in osteopetrotic mutant mice of Mitf(mi)/Mitf(mi)
H Watanabe1, K Tatsumi, H Yokoi
1Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Japan.
Abstract:
Mutation within the Mitf gene causes, in microphthalmic Mitf(mi)/Mitf(mi) (mi/mi) mice, multiple defects, including white coat color and functional defects in macrophages and osteoclasts. Our previous mating experiments have demonstrated that the mi mutation reduces the numbers of newborns and induces uterine inversion at delivery. The present study was designed to determine the causes of these pregnancy defects. The histology and number of F4/80-positive macrophages were not different between the ovaries of 23-day-old mi/mi and +/+ mice given eCG 48 h earlier. When ovulation was induced in these mice by hCG, the number of ovulated ova was significantly smaller in mi/mi mice than in wild-type (+/+) mice (p < 0.05). When bone marrow cells from +/+ mice were transplanted i.p. into 42 mi/mi female newborns, successful transplantation was observed in 16 of them at 20 days after birth. In one of these, the upper incisors had erupted. The mean number of tubal ova in mi/mi mice significantly increased after transplantation (p < 0.05) and was almost equal to that of +/+ mice. No uterine inversion occurred at 6 deliveries in 5 mi/mi females after bone marrow transplantation, while it occurred at 4 of 5 deliveries in mi/mi females during the same observation period (p < 0.05). These results indicate that bone marrow-derived cells, defective in mi/mi mice, are necessary for normal ovulation and delivery; the findings are consistent with the notion that macrophages play major roles in ovulation.
Insights
The Mitf gene mutation in mice causes infertility and delivery complications. Bone marrow transplantation corrected ovulation and delivery issues, suggesting a crucial role for bone marrow-derived cells, particularly macrophages, in reproductive success.
Area of Science:
- Genetics and Developmental Biology
- Reproductive Biology
- Immunology
Background:
- The Mitf gene mutation (mi/mi) in mice leads to defects in coat color, macrophages, and osteoclasts.
- Previous studies indicated that the mi mutation negatively impacts newborn numbers and causes uterine inversion during delivery.
Purpose of the Study:
- To investigate the underlying causes of pregnancy defects associated with the Mitf gene mutation.
- To determine the role of bone marrow-derived cells in ovulation and delivery in mi/mi mice.
Main Methods:
- Compared ovulation rates in mi/mi and wild-type mice after hCG induction.
- Transplanted wild-type bone marrow cells into newborn mi/mi female mice.
- Monitored pregnancy outcomes, including ovulation, delivery, and uterine inversion, post-transplantation.
Main Results:
- mi/mi mice exhibited significantly lower ovulation rates compared to wild-type mice.
- Bone marrow transplantation in mi/mi mice restored ovulation rates to near wild-type levels.
- Uterine inversion was significantly reduced in mi/mi mice following bone marrow transplantation.
Conclusions:
- Bone marrow-derived cells, which are defective in mi/mi mice, are essential for normal ovulation and successful delivery.
- Macrophages, derived from bone marrow, appear to play a critical role in the ovulatory process.