Understanding the trade-off between the environment and fertility in cows and ewes

Abstract

The environment contributes to production diseases that in turn badly affect cow performance, fertility and culling. Oestrus intensity is lower in lame cows, and in all cows 26% potential oestrus events are not expressed (to avoid getting pregnant). To understand these trade-offs, we need to know how animals react to their environment and how the environment influences hypothalamus-pituitary-adrenal axis (HPA) interactions with the hypothalamus-pituitary-ovarian axis (HPO). Neurotransmitters control secretion of GnRH into hypophyseal portal blood. GnRH/LH pulse amplitude and frequency drive oestradiol production, culminating in oestrus behaviour and a precisely-timed GnRH/LH surge, all of which are disrupted by poor environments. Responses to peripheral neuronal agents give clues about mechanisms, but do these drugs alter perception of stimuli, or suppress consequent responses? In vitro studies confirm some neuronal interactions between the HPA and HPO; and immuno-histochemistry clarifies the location and sequence of inter-neurone activity within the brain. In both species, exogenous corticoids, ACTH and/or CRH act at the pituitary (reduce LH release by GnRH), and hypothalamus (lower GnRH pulse frequency and delay surge release). This requires inter-neurones as GnRH cells do not have receptors for HPA compounds. There are two (simultaneous, therefore fail-safe?) pathways for CRH suppression of GnRH release via CRH-Receptors: one being the regulation of kisspeptin/dynorphin and other cell types in the hypothalamus, and the other being the direct contact between CRH and GnRH cell terminals in the median eminence. When we domesticate animals, we must provide the best possible environment otherwise animals trade-off with lower production, less intense oestrus behaviour, and impaired fertility. Avoiding life-time peri-parturient problems by managing persistent lactations in cows may be a worthy trade-off on both welfare and economic terms - better than the camouflage use of drugs/hormones/feed additives/intricate technologies? In the long term, getting animals and environment in a more harmonious balance is the ultimate strategy.

Keywords: GnRH; adrenal; behaviour; neurotransmitters; oestrus.

Figure 1. (a) Days from calving to pregnancy after AI in cows with different clinical production diseases (RFM retained fetal membranes; BCS body condition score). Adapted from Dobson et al. (2008); reproduced with permission; (b) Mean percentage of total embryos recovered (±SEM) representing cleaved embryos, live embryos (quality Grades 1-3) and high quality embryos (Grades 1 and 2) obtained from donors without (open bars) or with prior non-uterine disease (black bar). Adapted from Ribeiro et al. (2016); reproduced with permission.

Figure 2. Endocrine events during the follicular phase of the oestrous cycle of ewes. Left, peripheral hormone patterns; right, sequence of regulatory steps; top, theoretical model of neuroendocrine processes involved in generating the GnRH/LH surge (timings as in lower panel). The numbers (1-4) represent steps for which there is evidence of interruption during adverse environmental stimuli (see text). Adapted from Battaglia et al. (1998, 2000) and Dobson et al. (2012); reproduced with permission.

Figure 3. Daily plasma concentrations of (a) progesterone (○) and oestradiol (●), and (b) internal diameters of dominant follicles (●, ○) and subordinate follicles (other symbols) in cows from the last observed oestrus. The horizontal bar indicates presence of half a progesterone releasing intravaginal device (0.5 PRID). RO: right ovary, LO: left ovary. Note the presence of dominant follicle (●) for 50 days, but functionally producing oestradiol for only ~ 25 days; then replaced by a second functional dominant follicle (○) from 55 days onward. Adapted from Noble et al. (2000); reproduced with permission.

Figure 4. Mean (± SEM) diameter of the largest follicle, peripheral plasma concentrations of LH, and ovarian secretion rates of androstenedione and oestradiol, in ewes treated with GnRH antagonist and hourly injections of LH. The latter were continued for 10 days or stopped on Day 6 (right panels). Adapted from Dobson et al. (1997); reproduced with permission.

Figure 5. Ewe hypothalamus-pituitary-adrenal responses (mean ± SEM) to 2 h transport (left panels) or insulin injection (right panels). Note different vertical axis between left and right panels; inverse proportions of AVP and CRH after transport or insulin; and decreases in ACTH and cortisol while the stimuli continue. Adapted from Dobson and Smith (2000b); reproduced with permission.

Figure 6. Location of neuronal nuclei in the ewe brain that regulate GnRH and corticotrophin-releasing hormone and arginine vasopressin secretion, indicating the spatial relationship between regions of the hypothalamus (medial preoptic area (mPOA), ventral medial nucleus (VMN) and arcuate nucleus (ARC) of the medial basal hypothalamus)) and the brain stem (A1 and A2 regions, the area postrema (AP) and the locus coeruleus (LC)). PVN: paraventricular nucleus. Adapted from Dobson et al. (2003); reproduced with permission.

Figure 7. Diagram indicating possible inter-action between neurones involved in GnRH/behaviour disruption following adverse stimuli imposed in the late follicular phase of the ewe. Noradrenergic cells in the brain stem project to both the paraventricular nucleus (PVN) and the medial preoptic area (mPOA). Adverse stimuli activate CRH/AVP neurones in the PVN. Changes in activity of beta-endorphin and dynorphin neurones in the arcuate nucleus (ARC) influence PVN and mPOA output. In the ARC, the activities of oestradiol receptor (ER) neurones (probably kisspeptin/dynorphin/neurokinin B; KNDy cells) are altered by adverse stimuli, as are ER cells in the ventromedial nucleus (VMN). In the median eminence, CRH, but not AVP, terminals and KNDy terminals are in close contact with GnRH terminals providing another site for the disruption of GnRH release. Positive or negative effects at cell bodies are circled. Adapted from original drawing by SPS Ghuman (Dobson et al. (2012); reproduced with permission).

Figure 8. Diagram of neurotransmitter cell influence (i.e., % cells c-Fos activated) in the hypothalamic arcuate nucleus (ARC), medial pro-optic area (mPOA) and ventro-medial nucleus (VMN) at different times during follicular phase of intact ewes with (dotted line) or without treatment with lipopolysaccharide toxin (LPS) at 28 hours; LH surge occurs at 40 hours. No dotted line indicates no difference from controls. Adapted from Fergani et al. (2014b, 2017); and Robinson et al. (1991).

Figure 9. Mean (± SEM) hours from first to last display of different oestrus behaviours after progesterone withdrawal in 22 control ewes, 21 ewes injected with 4 IU/kg insulin (non-delayed n=10, delayed n=11) at 28 and 30 h, and 10 ewes injected with 100 ng/kg LPS at 28 h after progesterone withdrawal. Also shown: mean plasma oestradiol concentrations (red line) and timing of the LH surge (with onset indicated by dashed vertical line). Within each panel, differences between the onsets of each behaviour are indicated by different letters at each end of each bar, respectively (P<0.05); differences between the duration of each behaviour are also indicated by the letters at the end of each bar (P<0.02). Differences in the timing of onset between panels are indicated with asterisks. Time of treatment is indicated with the arrows. *P<0.05 compared to controls and insulin-non-delayed groups, **P<0.001 compared to control and both insulin groups, ***P<0.001 compared to controls and insulin-non-delayed groups. ****P<0.05 compared to controls and insulin subgroups. Adapted from Fergani et al. (2012); reproduced with permission.

Figure 10. In the ewe at luteolysis, plasma progesterone decreases and oestradiol increases. Oestrus behaviour is initiated (1) when oestradiol reaches a threshold and remains high for 6–10 h. Simultaneously, oestradiol also induces a surge of GnRH in portal blood (2), and LH in the periphery (3). Co-incident with the LH surge, oestradiol declines to basal concentrations while GnRH secretion stays high for an additional 24–36 h, while oestrus behaviour continues (4). One role of progesterone priming (P) is to increase the magnitude of the GnRH surge (broken arrow). Ovulation (black arrow) is precisely timed occurring 22–26 h after the LH surge. Adapted from Caraty et al. (2002); reproduced with permission.