CARTPT and FSH Signaling in Ovarian Follicle Development as an Emerging Link to Oocyte Quality and Female Infertility

Abstract

Not all ovarian follicles respond to follicle-stimulating hormone (FSH) in the same way. This difference is usually attributed to FSH receptor expression and local ovarian factors, but the role of CARTPT has received far less attention. Studies in granulosa cells have shown that cocaine- and amphetamine-regulated transcript (CART) can reduce FSH-induced cAMP production, aromatase expression, and estradiol synthesis. CARTPT expression has also been found to be higher in subordinate and atretic follicles in several animal models. Its regulation by leptin suggests a possible connection between metabolic status and follicular function. Early human findings have linked follicular CART expression with ovarian response and oocyte yield. In cattle and buffalo, CART suppressed FSH-stimulated cAMP production, aromatase expression, and estradiol output in granulosa cells and marked follicles destined for atresia, a pattern not confirmed in the one available porcine study. The receptor mediating these effects in the ovary remains unidentified, though a CART receptor was recently confirmed in another endocrine tissue. Human evidence linking CARTPT to ovarian response and oocyte quality remains preliminary and correlative. CARTPT therefore emerges as a mechanistically well-supported but clinically unproven contributor to FSH resistance and impaired oocyte quality, and this review outlines the loss-of-function and prospective human studies needed to establish its clinical relevance.