Nanodelivery System for Ovsynch Protocol Improves Ovarian Response, Ovarian Blood Flow Doppler Velocities, and Hormonal Profile of Goats

SIMPLE SUMMARY: Drug delivery systems depending on nanotechnology have been recently created to improve biological activity of drugs including hormones. Nanoformulated drugs have different pharmacokinetic properties in biological systems compared to their conventional forms due to the acquired new physicochemical properties such as lesser size, high size-to-weight ratio, and different surface charges and shapes. These properties enable them to efficiently deliver into target sites coping with existing biological barriers. Ovsynch protocol, GPG, is one of the most important estrous synchronization protocols due to the possibility of applying timed insemination with this protocol. This protocol is commonly used in many farm animals, as it aids in herd management and eliminates the need for the detection of estrus. However, there are still some shortcomings that restrict the outcomes of this protocol, such as scattering ovulation time, short luteal phase and inadequate luteal function, and low conception rates. Therefore, this study aims to evaluate ovarian response, blood flow of the ovarian and luteal arteries, and hormonal profile of goats receiving either a standard Ovsynch protocol or an Ovsynch protocol delivered via a nanodelivery system with different dosages of hormones. The present study is the first one that poses the idea that the nanodelivery system for the Ovsynch protocol enables lower hormone dose administration and improves the results of the protocol by inducing tighter synchrony of ovulation and better luteal function of synchronized goats. ABSTRACT: Fifteen cyclic, multiparous goats were equally stratified and received the common Ovsynch protocol (GPG: intramuscular, IM, injection of 50 mg gonadorelin, followed by an IM injection of 125 µg cloprostenol 7 days later, and a further IM injection of 50 mg gonadorelin 2 days later) or the Ovsynch protocol using nanofabricated hormones with the same dosages (NGPG) or half dosages (HNGPG) of each hormone. The ovarian structures and ovarian and luteal artery hemodynamic indices after each injection of the Ovsynch protocol using B-mode, color, and spectral Doppler scanning were monitored. Levels of blood serum progesterone (P(4)), estradiol (E(2)), and nitric oxide (NO) were determined. After the first gonadotrophin-releasing hormone (GnRH) injection, the number of large follicles decreased (p = 0.02) in NGPG and HNGPG, compared with GPG. HNGPG resulted in larger corpus luteum (CL) diameters (p = 0.001), and improved ovarian and luteal blood flow, compared with GPG and NGPG. Both NGPG and HNGPG significantly increased E(2) and NO levels compared with GPG. HNGPG increased (p < 0.001) P(4) levels compared with GPG, whereas NGPG resulted in an intermediate value. After prostaglandin F(2α) (PGF(2α)) injection, HNGPG had the largest diameter of CLs (p = 0.001) and significantly improved ovarian blood flow compared with GPG and NGPG. Both NGPG and HNGPG increased (p = 0.007) NO levels, compared with GPG. E(2) level was increased (p = 0.028) in HNGPG, compared with GPG, whereas NGPG resulted in an intermediate value. During the follicular phase, HNGPG increased (p = 0.043) the number of medium follicles, shortened (p = 0.04) the interval to ovulation, and increased (p < 0.001) ovarian artery blood flow and levels (p < 0.001) of blood serum P(4), E(2), and NO, compared with GPG and NGPG. During the luteal phase, the numbers of CLs were similar among different experimental groups, whereas the diameter of CLs, luteal blood flow, and levels of blood serum P(4) and NO increased (p < 0.001) in HNGPG, compared with GPG and NGPG. Conclusively, the nanodelivery system for the Ovsynch protocol could be recommended as a new strategy for improving estrous synchronization outcomes of goats while enabling lower hormone dose administration.