Administration of a long-term release GnRH superagonist during the canine postnatal critical window

FAYA, M.; PRIOTTO, M.; MARCHETTI, C.; GRISOLIA, M.

Boston

Simposio; Contraception and Fertility Control in Dogs and Cats; 2018

Contraception and Fertility Control in Dogs and Cats

The blockade of the pituitary-gonadal axis in the postnatal critical window has shown anegative impact on the development of the genital tract and subsequent reproductive function inseveral species. GnRH analogs have been used as endocrine disruptors during the criticalpostnatal time window in rodents, primates and felids. The objective of this study was to assessthe efficiency and clinical safety of the early postnatal administration of a high dose of deslorelinacetate on canine puberty postponement. Secondly, sexual steroids and histological gonadalchanges were also described. Twenty- four littermate, postnatal, mongrel dogs were randomlyassigned to implants of deslorelin acetate (Suprelorin,Virbac, France) 18.8 mg SC (DESLO;n = 12) or placebo (PLACE; n = 12) within the first 24h after birth. The dogs were seriallyfollowed up (behavioral and libido observation, physical examination, vaginal cytology,spermograms, and testosterone [T] and estradiol-17β [E2] serum determinations) up to pubertywhen they were spayed/ castrated. After surgery the gonads were grossly and microscopicallyexamined. At the time of writing, all PLACE (median 259 days) and 9/12 DESLO (median 574days) dogs have already attained puberty (P 0.1) and body weight (P > 0.1) did not differ throughout thetrial. Both groups of dogs finished growing at similar age (P> 0.05) independently of the pubertalstatus. No clinical side effect including the ?flare up effect? appeared in any animal (P > 0.1). Atpuberty, libido appeared normal in all the dogs (p>0.1) and all the bitches ovulated duringestrous cycle (P>0.1). In the females that were mated, gestations were confirmed in 2/2 and 5/6(P>0.1) of the DESLO and PLACE groups, respectively. In male dogs, serum T remained low(< 0.2 ng/mL) up to weeks 57.3±5.6 and 16.8±1.8 in DESLO and PLACE groups, respectively(P < 0.05). From those weeks on, T gradually began to increase up to puberty. In all the females,E2 concentrations remained low (< 5 pg/mL) throughout the trial except in peripubertal andpubertal determinations in which the values were > 12 pg/mL. The histomorphometrical study ofthe gonads revealed no differences for the ovaries (P > 0.1) and a decrease in the germinalepithelium (P< 0.01) and Sertoli cells (P < 0.05). It was concluded that 18.8 mg of deslorelinacetate at the early neonatal period decreased sexual steroids postponing puberty without side effects.