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Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice
Mara Sandrock1, Angela Schulz, Claudia Merkwitz
1Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany. mara.sandrock@medizin.uni-leipzig.de
Abstract:
Obese melanocortin-4-receptor-deficient (MC4R-/-) male mice are reported to have erectile dysfunction, while homozygous MC4R-/- female mice are apparently fertile. A recently established obese mouse strain, carrying an inactivating mutation in the MC4R gene, revealed difficulties in breeding for the homozygous female mice. This prompted us to determine the presence of follicles and corpora lutea (CL) in ovaries of MC4R-/- mice aged 3-6 months in comparison to wild type (MC4R+/+) littermates. Serial sections of formaldehyde-fixed ovaries of mice with vaginal signs of estrus and metestrus were assessed for the number of healthy and regressing follicles and CL. The number of CL, as an estimate for the ovulation rate, decreased to zero during aging in MC4R-/- mice. The number of small- (diameter 100-200 micrometer) and large-sized follicles namely antral follicles (diameter >200 micrometer) were slightly increased in MC4R-/- compared to MC4R+/+ mice. Greater differences were found in very large to cystic follicles, which were more numerous in MC4R-/- mice. The number of regressing antral follicles was higher in the MC4R-/- group compared to the MC4R+/+ group. This was associated with a wide range in the number of collapsed zonae pellucidae as the last remnants of regressed follicles. A conspicuous hypertrophy of the interstitial cells was noted in 6-month-old MC4R-/- mice. In conclusion, cystic follicles and the reduction in CL number point to a decreased ovulation rate in obese MC4R-/- mice.
Insights
Obese melanocortin-4-receptor-deficient (MC4R-/-) female mice exhibit impaired fertility due to a reduced ovulation rate. Their ovaries show fewer corpora lutea (CL) and more cystic follicles, indicating reproductive challenges in these mice.
Area of Science:
- Reproductive biology
- Endocrinology
- Obesity research
Background:
- Obesity is linked to reproductive dysfunction.
- Melanocortin-4-receptor (MC4R) deficiency causes obesity.
- MC4R-/- female mice are reportedly fertile, but breeding difficulties suggest otherwise.
Purpose of the Study:
- To investigate ovarian function in MC4R-/- mice.
- To compare follicle and corpora lutea (CL) counts in MC4R-/- and wild-type mice.
- To determine the impact of MC4R deficiency on ovulation rate.
Main Methods:
- Ovarian tissue from MC4R-/- and MC4R+/+ mice (3-6 months old) was analyzed.
- Histological assessment of follicles and CL in serial ovarian sections.
- Quantification of healthy, regressing follicles, and CL.
Main Results:
- Corpora lutea (CL) count decreased to zero with age in MC4R-/- mice.
- MC4R-/- mice showed increased numbers of large, cystic follicles.
- Higher rates of regressing antral follicles and interstitial cell hypertrophy were observed in MC4R-/- mice.
Conclusions:
- MC4R deficiency in mice leads to a decreased ovulation rate.
- Cystic follicle development and reduced CL formation indicate impaired fertility.
- MC4R signaling is crucial for normal ovarian function and ovulation.
