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Title: The Impact of Dietary Protein on Reproductive Performance in Rodents (Rats and Mice)
Contributor(s): Ajuogu, Peter Kelechi  (author); Smart, Neil  (supervisor)orcid ; McFarlane, James Robert  (supervisor)orcid ; Hart, Robert  (supervisor)orcid 
Conferred Date: 2020-02-07
Copyright Date: 2019-08
Thesis Restriction Date until: 2025-02-07
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Related DOI: 10.1093/jas/skz380

Good nutrition is essential for optimal growth and reproduction in both animals and man and dietary protein balance in the diet is an important component of adequate nutrition. Several research efforts in the last decade, have been developed to determine on whether high-protein and or low protein diets have a significant impact on reproduction in the dams and her offspring, however several studies have led to contradictory results and conclusions. In this study we tested the hypothesis that dietary protein levels are related to changes in morphofunctional parameters associated with reproductive successes in rodents.

From the results, we found protein dietary levels to influence the reproductive outcomes in rats and low protein diet as one of the root causes of male factor infertility affecting both the gonad and its endocrine status directly on the males and indirectly on the male offspring. We also deduce that maternal low protein diet leads to fetal programming of metabolic and reproductive dysfunction in both the male and female offspring later in life.

In chapter 2, we systematically reviewed and meta-analysed 12 published articles searched from that met the eligibility criteria to evaluate the effect of low protein in the diet on the fertility potentials of male rats. The outcome of the analysis revealed that low protein in the diet significant reduction (P<0.05) on the testis, epididymis and seminal vesicles and body weights, serum testosterone, and follicle-stimulating hormone (FSH) concentrations when compared with the control except luteinizing hormones (LH) that was not significantly affected (P>0.05) by the protein treatments. These implies a negative association with the reproductive axis (hypothalamicpituitary-gonadal axis). We infer, therefore, that sub-optimal protein diet is associated with male factor infertility in rats.

To determine whether low or high protein diet will alter reproductive outcomes: we utilized a systematic review and meta-analysis of controlled trials in rats in chapter 3. Data on the outcome measures were extracted and pooled across trials using random-effects model and expressed as mean differences (MD) at a 95% confidence interval (Cl). We found low protein diets to significantly reduce litter weight (P=0.00001) and gestational weight gain (P=0.0001) but did not influence litter size (p=0.66) or gestational feed intake (P=0.29). In contrast, high protein diets reduced gestational feed intake (p=0.04) but did not influence litter size (P=0.71), litter weight (P=0.18) and gestational weight gain. From the results, we confirm that low and high gestational protein diets alter reproductive outcomes at birth in rats. These also emphasize the importance of exercising caution when manipulating gestational diets to achieve enhanced reproductive outcomes and weight management during gestation.

In chapter 4, we synthesized 29 published studies that met our selection criteria to determine whether gestational low protein in the diet during pregnancy influence placental development and alters endocrine profile in pregnant rats. Data were pooled across studies by the generic inverse variance method and expressed as mean differences at 95% confidence intervals. The results indicate maternal low protein diet detrimentally reduced placental weight (P=0.00001) and progesterone concentration (P=0.02). Also, plasma prolactin concentration was significantly increased (P=0.01) in the maternal low protein treated group compared with the control indicating negative maternal adaptations. We infer that low dietary protein in gestational rats is associated with reduced placental weight and alteration in the reproductive endocrine profile. Experimental studies are necessary to elucidate the mechanisms that caused these changes.

In chapter 5, we conducted a systematic review and meta-analysis to determine whether in utero low protein dietary exposure during fetal/neonatal development will significantly impact on the classical markers of fertility in the adult male rats. Eleven studies met our inclusion criteria and were used for the analysis using random effect models and expressed as mean differences (MDs) at 95% CIs for each study. We found detrimental alterations in form of reduction in the testis weight (P=0.00001), sperm count (P=0.0007), number of Sertoli cells (P=0.004) and testosterone (T) concentration (P=0.0003), in comparison with controls. In contrast, follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations were different between groups. These implies a detrimental associations with classical male fertility markers (the testicular weight, and Sertoli cell number, serum testosterone and sperm count) and are consistent with thrifty phenotype hypothesis which state that subjecting an individual either excess or poor nutrition in utero can lead to an adaptation of fetal metabolism and can programming susceptibility of the fetus to developmental programming of adult diseases later in life. The mechanisms of action responsible for these phenomena need further investigation.

In the same vain, in chapter 6, we synthesized 14 studies to determine whether low protein diet will alter the reproductive phenotype of female offspring born to maternal low protein restricted dams. The ovarian weight (P=0.04), estrogen (P=0.004) and leptin (P=0.03) concentrations were significantly reduced in our analyses these implies a negative association with fertility potentials. The decreased ovarian weight and reduced estrogen and leptin concentration indicates a link between gestational low protein diet and compromised hypothalamic-pituitary-gonadal axis. The outcome of this analyses presents relevant data for health and nutritional professionals to establish appropriate nutritional intervention to prevent transgenerational adult reproductive diseases.

In the experimental chapter (Chapter 7), we assessed whether high or low protein diet during the periconceptional period will significantly impact on the plasma biochemistry and reproductive performance in mice dams over an 8-week period. Adult virgin fertile female (n=60), were randomly distributed equally to three experimental groups, according to their diets, which contained different dietary protein levels; low (8%); high protein (35%) or adequate protein diet (control, 22%) for 6 weeks before mating and until day 10 of pregnancy. Body weights were not different between groups, but the conception rate for the low protein group was significantly lower than either the control or high protein groups. The embryo numbers were significantly lower in the low protein group compared to the control and high protein groups. Blood urea nitrogen and glucose were significantly lower and cholesterol higher in the low protein group. These results suggest that diets low in protein have a negative impact on fertility and although blood glucose levels are low, cholesterol levels are elevated.

This thesis has provided novel insights that low protein diet directly or indirectly impairs fertility in males affecting both the gonads and its endocrine status as reflected in the reduction of the gonadal weight and alteration of the endocrine profile directly on the males and indirectly on the male offspring. The offspring of protein restricted dams can adjust on the short term the detrimental intra uterine environment, to ensure survival, however, on the long run, predisposes it to feature reproductive dysfunctions and infertility. The novel finding of low plasma glucose levels precipitated by the periconceptional low protein diet is an insight into the mechanism by which poor quality diets impact the offspring. This study supports the notion that global burden of reproductive pathologies can be prevented through adequate nutritional counselling and updating the global dietary guidelines for effective reproductive programme. Future research and collaboration across relevant stakeholders are required to drive this programme.

Publication Type: Thesis Doctoral
Fields of Research (FoR) 2008: 110306 Endocrinology
Fields of Research (FoR) 2020: 310910 Animal physiology - systems
300305 Animal reproduction and breeding
320208 Endocrinology
Socio-Economic Objective (SEO) 2008: 920106 Endocrine Organs and Diseases (excl. Diabetes)
920114 Reproductive System and Disorders
Socio-Economic Objective (SEO) 2020: 100412 Sheep for meat
HERDC Category Description: T2 Thesis - Doctorate by Research
Description: Please contact if you require access to this thesis for the purpose of research or study.
Appears in Collections:School of Science and Technology
Thesis Doctoral

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