The “ram effect”: new insights into neural modulation of the gonadotropic axis by male odors and socio-sexual interactions

Abstract

Reproduction in mammals is controlled by the hypothalamo-pituitary-gonadal (HPG) axis under the influence of external and internal factors such as photoperiod, stress, nutrition, and social interactions. Sheep are seasonal breeders and stop mating when day length is increasing (anestrus). However, interactions with a sexually active ram during this period can override the steroid negative feedback responsible for the anoestrus state, stimulate luteinizing hormone (LH) secretion and eventually reinstate cyclicity. This is known as the “ram effect” and research into the mechanisms underlying it is shedding new light on HPG axis regulation. The first step in the ram effect is increased LH pulsatile secretion in anestrus ewes exposed to a sexually active male or only to its fleece, the latter finding indicating a “pheromone-like” effect. Estradiol secretion increases in all ewes and this eventually induces a LH surge and ovulation, just as during the breeding season. An exception is a minority of ewes that exhibit a precocious LH surge (within 4 h) with no prior increase in estradiol. The main olfactory system and the cortical nucleus of the amygdala are critical brain structures in mediating the ram effect since it is blocked by their inactivation. Sexual experience is also important since activation (increased c-fos expression) in these and other regions is greatly reduced in sexually naïve ewes. In adult ewes kisspeptin neurons in both arcuate and preoptic regions and some preoptic GnRH neurons are activated 2 h after exposure to a ram. Exposure to rams also activates noradrenergic neurons in the locus coeruleus and A1 nucleus and increased noradrenalin release occurs in the posterior preoptic area. Pharmacological modulation of this system modifies LH secretion in response to the male or his odor. Together these results show that the ram effect can be a fruitful model to promote both a better understanding of the neural and hormonal regulation of the HPG axis in general and also the specific mechanisms by which male cues can overcome negative steroid feedback and trigger LH release and ovulatory cycles.

Progesterone (P4), luteinizing hormone (LH) levels and ovarian activity in postpartum Santa Inês ewes subject to a male effect

“…This similarity between results is in agreement with similar incidences of short estrus cycles and the number of ovulations between groups. Due to these facts, the determination of LH levels at 4 h intervals was efficient to capture the preovulatory peak as described in other reports (Chanvallon et al, 2011;Fabre-Nys et al, 2015).…”

“…Three ewes from each group were randomly chosen for LH analysis after the introduction of rams. Blood sampling for LH analysis was at 4 h intervals and performed during a period of 4 days after the introduction of rams, as described by Chanvallon et al (2011) and Fabre-Nys et al (2015. Moreover, ewes used for LH evaluation were excluded from further analysis in order to avoid any effect of excessive handling on estrus and pregnancy rates.…”

Reproductive performance of postpartum ewes treated with insulin or progesterone hormones in association with ram effect

“…Blood sampling for LH analysis was performed during a period of four days after introduction of ram in four‐hour intervals, as described by Chanvallon et al. () and Fabre‐Nys, Kendrick, and Scaramuzzi (), Fabre‐Nys et al. ().…”

“…Ewes under postpartum anoestrus are directly dependent upon P4 and indirectly on insulin for preovulatory synthesis of GnRH and LH (Evans et al, 2004;Fabre-Nys et al, 2016;Peclaris et al, 1999;Umberger, Jabbar, & Lewis, 1994;Ungerfeld, Forsberg, & Rubianes, 2004). Moreover, the association between these compounds and the ram effect may increase the reproductive efficiency in sheep.…”

Effect of Nutrition, Lactation and Gonadotropin Stimulation on Ram-Induced LH Surge and Subsequent Fertility in Early Post-Partum Ewes during Seasonal Anestrous

“…The third wave of ovulation will then be accompanied by estrous behavior around 22-28 days after ram introduction. Ewes that have normal luteal phase which last for about 10 days after the first silent ovulation can exhibit sexual behavior around 17-20 days after initial introduction of rams (Fabre-Nys et al, 2015).…”