Sexual differentiation of reproductive neuroendocrine function in sheep

Abstract

Puberty, the transition from a sexually immature state to one of full reproductive activity, is timed by signals acting in the brain to increase activity of the hypothalamo-pituitary axis which stimulates the production of mature gametes. There are profound sex differences in the timing of puberty in many species. This occurs by sexual differentiation of the neuroendocrine control of pituitary gonadotrophin secretion. Studies using sheep as an experimental model have defined some of the factors responsible for this developmental difference in reproductive neuroendocrine function. We have studied the prenatal organizers (prenatal steroids), postnatal cues (growth and photoperiod responses) and the effectors (GnRH neurones) that time the pubertal process. Our experimental strategy has been to conduct complementary anatomical and physiological investigations to link form and function in the sexual differentiation of reproductive neuroendocrine function. Reproductive strategies in males and femalesTo ensure that sexual activity will ultimately be successful, males and females respond to cues from both their internal and external environments. Mating is timed so that young are born when somatic conditions are appropriate and seasonal conditions are favourable. However, the differences in reproductive strategies between males and females can often be as wide as those between different species (Bronson, 1989). These differences arise because the time course of gametogenesis and the metabolic investments in reproduction can be quite different in the two sexes.The typical female mammal gives birth to relatively few offspring during her lifespan, but expends considerable energy in their growth and early development (for review, see Bronson, 1989). Thus, most of her reproductive effort is invested after mating. The metabolic demands of pregnancy and lactation are considerable, and can compromise the chances of survival of the female if begun at an inappropriate time. However, the gametic cycle of females is relatively short, and only a few days are required to develop a preovulatory follicle. Together, these factors encourage the immature female to delay sexual maturation until conditions are optimal. After puberty, the typical adult female living in natural conditions may have only a few fertile cycles in 1 year. For much of the year, she is reproductively suppressed as a result of pregnancy and lactation, seasonal anovulation or, possibly, inadequate food intake. Nonetheless, once internal and external cues are favourable, reproductive activity can be initiated rapidly.The male uses an entirely different strategy to time sexual activity. The typical polygynous male produces large numbers of offspring, but does little to ensure their survival. Thus, most of the energy for his reproductive effort is expended before mating, primarily in competition for females (Bronson, 1985). Even though the energetic demands for production of spermatozoa and seminal fluid are comparatively small, spermatogenesis takes weeks to months to c...

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

“…T exposure within a narrower window around the normal T peak will masculinize sexual behavior and the brain regions that control it 94 , 95 In contrast, low doses of T throughout this critical window will have no effect on genitalia, behavior, or adult basal LH release, but will partially impair LH surges. 96 …”

Profiling γ-Aminobutyric Acid (GABA_A) Receptor Subunit mRNA Expression in Postnatal Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mouse with Single Cell RT-PCR

“…The secretory activity of GnRH neurons is sexually differentiated with the two most robust sexual dimorphisms being the presence of the GnRH/LH surge in the female and the more rapid increase in LH secretion following gonadectomy in the male [1, 2, 3, 4, 5, 6, 7, 8, 9]. Whole animal studies have indicated a role for GABA, acting through the GABA A receptor, in the generation of the LH surge as well as the negative feedback influence of estrogen on GnRH neurons [11, 19, 20, 21, 23].…”

“…Although GnRH is secreted in a pulsatile fashion in both males and females, it is clear that major sex differences exist in the postnatal development and precise patterning of GnRH and gonadotropin release [1]. Most dramatically, the occurrence of the preovulatory estrogen-induced GnRH surge is restricted to the female in many species [1, 2, 3, 4, 5, 6], although sex differences are also encountered in terms of the ‘negative feedback’ effects of gonadal steroid hormones [7, 8, 9]. …”

“…It is thought that the sexually dimorphic nature of the GnRH neurons arises through classical ‘organizational’ mechanisms [10]in which embryonic or perinatal exposure of the male brain to testosterone masculinizes the GnRH network [1, 11]. However, the molecular and cellular impact of this steroid exposure upon the GnRH neurons remains unclear.…”

Steroidogenic versus Metabolic Programming of Reproductive Neuroendocrine, Ovarian and Metabolic Dysfunctions

“…Nevertheless, pregnancy rate in GD60–90 females was only 40% compared with controls that presented a 90% pregnancy rate [16]. Fertility testing is not possible in GD30–90 females, which are phenotypically virilized [17]. Studies carried out to determine the impact of metabolic status and adiposity found that postnatal overfeeding amplifies the severity of the reproductive phenotype in GD30–90 females with majority becoming anovulatory in the first breeding season [18].…”