Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor beta knockout mice

Objective: To study the role of estrogen receptor beta in follicle development and maturation and in the response to gonadotropin stimulation aiming at superovulation. Animals: Healthy wild-type and estrogen receptor beta (ERβ) knockout female mice aged 4 weeks, 7 weeks, and 6 months. analysis. Main Outcomes: Oocyte yield after superovulation, transcriptomic profiling of cumulus cells and oocytes and immunohistochemical analyses. Results: Superovulation of ERβ knockout (Esr2-KO) mice results in reduced oocyte yield at 6-months of age compared to wild-type (WT) mice. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERβ in bipotential granulosa cell cluster. Loss of ERβ increased expression of the other estrogen receptors Esr1 and Gper1. Conclusion: Our results show that ERβ has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors supports a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.