The naturally occurring luteinizing hormone surge is diminished in mice lacking estrogen receptor Beta in the ovary
Friederike L Jayes1, Katherine A Burns, Karina F Rodriguez
1Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
Abstract:
Female ESR2-null mice (betaERKO) display defects in ovarian function and are subfertile. Follicular maturation is impaired and explains smaller litters, but betaERKO also produce fewer litters, which may be partially due to inadequate ovulatory signals. To test this, the amplitude and timing of the naturally occurring luteinizing hormone (LH) surge was measured in individual intact betaERKO and wild-type (WT) mice. Vaginal cytology was evaluated daily, and blood samples were taken from mice in proestrus. The amplitude of the LH surge was severely blunted in betaERKO mice compared to WT, but pituitary LH levels revealed no differences. The betaERKO mice did not produce a preovulatory estradiol surge. To determine if the smaller LH surges and the reduced number of litters in betaERKO were due to the lack of ESR2 in the hypothalamic-pituitary axis or due to the absence of ESR2 in the ovary, ovaries were transplanted from WT into betaERKO mice and vice versa. The size of the LH surge was reduced only in mice lacking ESR2 within the ovary, and these mice had fewer litters. Fertility and size of the LH surge were rescued in betaERKO mice receiving a WT ovary. These data provide the first experimental evidence that the LH surge is impaired in betaERKO females and may contribute to their reduced fertility. ESR2 is not necessary within the pituitary and hypothalamus for the generation of a normal LH surge and for normal fertility, but ESR2 is essential within the ovary to provide proper signals.
Insights
Estrogen receptor 2 (ESR2) is essential in the ovary for signaling that triggers ovulation. Lack of ESR2 in the ovary impairs the luteinizing hormone (LH) surge, reducing fertility in female mice.
Area of Science:
- Reproductive biology
- Endocrinology
- Genetics
Background:
- Female mice lacking estrogen receptor 2 (ESR2), known as betaERKO mice, exhibit ovarian dysfunction and subfertility.
- While impaired follicular maturation contributes to smaller litter sizes, reduced litter frequency suggests additional factors like inadequate ovulatory signals may be involved.
Purpose of the Study:
- To investigate the role of estrogen receptor 2 (ESR2) in regulating the luteinizing hormone (LH) surge and its impact on fertility in female mice.
- To determine whether ESR2's function in the hypothalamic-pituitary axis or the ovary is critical for normal ovulatory signaling and reproductive success.
Main Methods:
- Measured the amplitude and timing of the LH surge in intact betaERKO and wild-type (WT) mice.
- Utilized ovarian transplantation between betaERKO and WT mice to dissect the site of ESR2 action.
- Assessed fertility and monitored vaginal cytology for estrous cycle evaluation.
Main Results:
- BetaERKO mice exhibited a significantly blunted LH surge amplitude compared to WT mice, without differences in pituitary LH levels.
- BetaERKO mice failed to produce a preovulatory estradiol surge.
- Ovarian ESR2 deficiency, not hypothalamic or pituitary ESR2 deficiency, was linked to reduced LH surge amplitude and fewer litters.
- Ovarian transplantation restored LH surge amplitude and fertility in betaERKO mice receiving a WT ovary.
Conclusions:
- Estrogen receptor 2 (ESR2) is crucial within the ovary for generating the proper signals that elicit a normal LH surge.
- The impairment of the LH surge in ESR2-deficient mice contributes to their reduced fertility.
- ESR2 is not required in the pituitary or hypothalamus for normal LH surge generation and fertility, but is essential in the ovary for reproductive signaling.
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