Fig. 1: Profound hypogonadotropic hypogonadism in adult KiDKO mice.

Representative images of the gonads (testes and ovaries) and sex organs (epididymis and uterus) for adult control and KiDKO mice of both sexes are presented in (a; males) and (f; females). For the latter, individual profiles of ovarian cyclicity, monitored by vaginal cytology, are also shown in (g). In addition, representative histological sections of the testis (b) and ovary (h) are presented for control and KiDKO mice. Control mice showed complete spermatogenesis in the lumen of seminiferous tubules, denoted by the presence abundant elongated spermatids (ES) and prominent Leydig cells (LC; inset) in the interstitium. In contrast, KO mice showed atrophic seminiferous tubules with spermatogenic arrest at the primary spermatocyte (PS) or round spermatid (RS) level, as well as poorly differentiated Leydig cells (LC; inset). In the case of the ovary, while control females showed cycling ovaries with abundant growing follicles and corpora lutea (CL), in KiDKO females, large antral follicles and corpora lutea were absent in KO mice, while preantral (PAF; see inset) or early antral follicles were the most advanced healthy growing follicles. In addition, testicular weight and tubular diameter in males (c; control n = 13, KiDKO n = 14 for testis weigh and control n = 5, KiDKO n = 5 for tubular diameter), and ovarian and uterus weight in females (i; control n = 7, KiDKO n = 16) are presented for control and KiDKO mice, for which serum LH and FSH levels are also shown (d; LH: control n = 6, KiDKO n = 5; and FSH: control n = 7, KiDKO n = 8; j; control n = 7, KiDKO n = 17 for LH levels and control n = 5, KiDKO = 18 for FSH levels). Finally, pulsatile secretory profiles of LH over a 180-min period were assessed in control and KiDKO animals (e; males: control n = 14, KiDKO n = 12; k; females: control n = 8, KiDKO n = 7); only representative profiles of male and female mice from both genotypes are shown. Note that results for LH pulsatility in KiDKO mice are also presented at a magnified scale in the insets. The values are represented as the mean ±  SEM. *P < 0.05; ***P < 0.001 vs. corresponding control groups.