Selective activation of LH-dependent transcriptional pathways determines ovulatory follicles in the hierarchical ovary of cloudy catshark

The number of offspring produced per reproductive cycle varies widely across animals and is constrained by the number of ovarian follicles that proceed to ovulation. In vertebrates, this phenomenon has been 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. Here we propose a novel mechanism that explains the difference between ovulatory (F1) and non-ovulatory (F2) follicles using the cloudy catshark as a model. The cloudy catshark possesses a hierarchical ovary and produces only two eggs per reproductive cycle. Both F1 and F2 follicles are capable of receiving and responding to LH, as evidenced by their comparable expression of lhr and the downregulation of lhr following LH surge. Nevertheless, LH stimulation selectively activates transcriptional programs associated with the ovulatory process exclusively in F1 follicles. These include progesterone production via star2 upregulation, as well as cancer-associated transcriptional pathways, including transcription factors runxs, prostaglandin-related genes (ptgs2 and ptger1), and matrix metalloproteinases. These results indicate that ovulatory and non-ovulatory follicles may exhibit qualitatively distinct transcriptional responses to the LH surge, potentially challenging the prevailing LHR-threshold model in vertebrates, in which LHR expression is considered a key determinant of ovulatory competence.