Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge

For 3.5 billion years before electric light was invented in 1879, life on Earth evolved under the pattern of light during the day and darkness during the night. Through evolution, nearly all organisms internalized the temporal rhythm of Earth’s 24-hour rotation and evolved self-sustaining biological clocks with a ~24-hour rhythm. These internal rhythms are called circadian rhythms, and the molecular constituents that generate them are called molecular circadian clocks. Alignment of molecular clocks with the environmental light-dark rhythms optimizes physiology and behavior. This is particularly true for reproductive function, in which seasonal breeders use day-length information to time yearly changes in fertility. However, it is becoming increasingly clear that light-induced disruption of circadian rhythms can negatively impact fertility in non-seasonal breeders as well. In particular, the luteinizing hormone surge promoting ovulation, is sensitive to circadian disruption. In this review, we will summarize our current understanding of the neuronal networks that underlie circadian rhythms and the luteinizing hormone surge.

To assess ovulation in infertile women using urinary luteinizing hormone surge kits versus transvaginal ultrasonography

Background: The study was conducted to evaluate the efficacy of urinary LH surge kits and TVS to detect ovulation in induced cycles and to compare the ovulation rates by both methods.Methods: Prospective experimental randomized control trial on 72 women with an ovulatory infertility aged 18-35 years, fulfilling the inclusion criteria were given letrozole for ovulation induction. All were randomly divided in two groups. Group 1 woman were asked to check ovulation by urinary LH surge kits and group 2 women were called for follicle monitoring by TVS.Results: Letrozole has no negative effect on endometrium; induced cycle has larger diameter of follicle (median: 22 mm). In induced cycle ovulation occurs later compared to normal cycle (D-16) and half of the women had a BMI more than the recommended WHO criteria (average was 25.28 kg/m2). Number of letrozole cycles (p=0.2642), dose requirement (p=0.0812) and pregnancy rates (10.26% versus 18.19%) were comparable in both groups.Conclusions: TVS is objective, accurate and thus standard modality for ovulation detection. LH surge kit is subjective, having more chances of error but can be used as a good alternative in certain settings like woman of remote area, woman having fear of invasive modality and COVID era woman who are afraid to visit hospital repeatedly.

Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish

The luteinizing hormone surge is essential for fertility as it triggers ovulation in females and sperm release in males. We previously reported that secretoneurin-a, a neuropeptide derived from the processing of secretogranin-2a (Scg2a), stimulates luteinizing hormone release, suggesting a role in reproduction. Here we provide evidence that mutation of thescg2aandscg2bgenes using TALENs in zebrafish reduces sexual behavior, ovulation, oviposition, and fertility. Large-scale spawning within-line crossings (n= 82 to 101) were conducted. Wild-type (WT) males paired with WT females successfully spawned in 62% of the breeding trials. Spawning success was reduced to 37% (P= 0.006), 44% (P= 0.0169), and 6% (P< 0.0001) forscg2a−/−,scg2b−/−, andscg2a−/−;scg2b−/−mutants, respectively. Comprehensive video analysis indicates thatscg2a−/−;scg2b−/−mutation reduces all male courtship behaviors. Spawning success was 47% in saline-injected WT controls compared to 11% in saline-injectedscg2a−/−;scg2b−/−double mutants. For these mutants, spawning success increased 3-fold following a single intraperitoneal (i.p.) injection of synthetic secretoneurin-a (P= 0.0403) and increased 3.5-fold with injection of human chorionic gonadotropin (hCG). Embryonic survival at 24 h remained on average lower inscg2a−/−;scg2b−/−fish compared to WT injected with secretoneurin-a (P< 0.001). Significant reductions in the expression of gonadotropin-releasing hormone 3 in the hypothalamus, and luteinizing hormone beta and glycoprotein alpha subunits in the pituitary provide evidence for disrupted hypothalamo-pituitary function inscg2aandscg2bmutant fish. Our results indicate that secretogranin-2 is required for optimal reproductive function and support the hypothesis that secretoneurin is a reproductive hormone.