cAMP responsiveness determines follicular ovulatory fate downstream of the LH receptor in the cloudy catshark

The number of offspring produced per reproductive cycle is generally explained by a luteinizing hormone receptor (LHR)-threshold model, in which only follicles expressing sufficient levels of LHR respond to the LH surge and proceed to ovulation. Using the cloudy catshark as a model, we reveal a distinct mechanism that determines the fate of ovulatory (F1) and non-ovulatory (F2) follicles independently of LHR abundance. The cloudy catshark produces only two eggs per reproductive cycle by ovulating a pair of F1 follicles from its single ovary. Both F1 and F2 follicles express comparable levels of lhr, indicating that both retain the capacity to receive the LH signal. Nevertheless, LH stimulation selectively activated ovulation-associated responses in F1 follicles. These included progesterone production via star2 upregulation, as well as transcriptional programs including RUNX transcription factors, prostaglandin signaling (ptgs2, ptger1), and matrix metalloproteinases. Moreover, direct activation of cAMP pathway, bypassing LHR activation, induced progesterone production in F1 but not F2 follicles, indicating that the critical difference in ovulatory responsiveness lies downstream of cAMP. These results demonstrate that follicular ovulatory fate is determined, at least in part, by follicle-specific transcriptional responses to cAMP, rather than by LHR abundance alone, challenging the prevailing LHR-threshold model of ovulatory regulation in vertebrates.