Physiological and molecular aspects of ovarian follicular developmental competence in sows

Natasja G.J. Costermans

Research output: Thesisinternal PhD, WU

Abstract

Modern sow lines have been genetically selected for increased litter size. This increase in litter size, however, is also associated with higher piglet mortality. This piglet mortality can be partly explained by lower piglet birth weights and higher within-litter variation in birth weight. The main hypothesis of this thesis is that these factors, the lower piglet birth weights and the higher within-litter variation, are (at least partly) explained by impaired follicular development of sows during and after lactation, as this is the period in which antral follicles develop that contain the oocytes that will give rise to the next litter. Increased litter size also results in increased metabolic demands of modern sows during lactation, due to the necessary higher milk production. As the metabolic state highly influences follicular development, the increased metabolic demands may therefore impair follicular development and contribute to lower piglet birth weights and higher within-litter variation in piglet birth weight. It is not clear, however, which metabolic processes play the most significant roles in influencing follicular developmental competence in modern sows.

Increased understanding of the origin of lower piglet birth weights in modern sows may be achieved by identification of molecular physiological characteristics which determine follicular developmental competence and how these are influenced by metabolism. Therefore, the aims of this thesis were: 1) To establish physiological and molecular characteristics of follicular developmental competence in sows and 2) To better understand physiological relations between the metabolic state of sows and follicular developmental competence.

This thesis describes results from two pig studies. In the first study, follicular development and oocyte quality were assessed in multiparous sows at the onset of the follicular phase (at weaning), while in the second study, follicular development and oocyte quality were assessed in primiparous sows at the mid-follicular phase (48 after weaning). In both studies, the metabolic state of the sows was assessed to investigate physiological relations between metabolism during lactation and follicular developmental competence. In the first study, multiparous sows were all full-fed during lactation, while in the second study, half of the primiparous sows were restricted-fed during the last two weeks of lactation.

In Chapter 2 of this thesis, I aimed to identify possible follicular causes of piglet birth weight variation by studying follicular development of multiparous sows at weaning in sows that differ in their estimated breeding value (EBV) for piglet birth weight variation (Study 1). In addition, relations between the metabolic state of these sows during lactation and follicular development were assessed. No significant relations between EBV for birth weight variation and any of the measured follicular or metabolic parameters were found. We did, however, find relations between metabolic losses and subsequent follicle development and –quality.  For example, average follicle size of the 15 largest follicles (the presumptive ovulatory follicle pool) was negatively related to serum creatinine levels, a marker for protein breakdown, and this follicle size was surprisingly, positively related to a higher backfat depth loss during lactation. As sows with a high backfat loss also had higher backfat levels at the start of lactation, it was hypothesised that modern sows with more backfat at the start of lactation are able to mobilise more energy from backfat during lactation to support follicular development thereby sparing protein reserves. To conclude, although unfortunately no relations between EBV and follicular development have been found, our study does show that energy mobilization from different sources during lactation, adipose tissues or muscle reflecting fat or lean mass, respectively, could have divergent effects on follicular development at weaning.

Identification of molecular physiological characteristics which determine follicular developmental competence, may provide new insights in the origin of lower piglet birth weights in sows. Therefore, follicular granulosa cell gene and protein expression and follicular fluid composition were assessed in relation to two follicular competence markers, average follicle size (Chapter 3) and cumulus-oocyte complex (COC) morphology (Chapter 4) in the sows of Study 1. 

In Chapter 3, I investigated granulosa cell processes in large and small follicles of the pool of 15 largest follicles (the presumptive ovulatory follicle pool). Granulosa cells of smaller antral follicles showed increased cell proliferation, which was accompanied by a metabolic shift towards aerobic glycolysis, similar to other highly proliferating cells. High granulosa cell proliferation rates in smaller follicles may be regulated via increased expression of receptors for locally produced mitogens, such as androgen receptor (AR) and epidermal growth factor receptor (EGFR). While granulosa cells of smaller follicles in the pool were more proliferative, granulosa cells of larger follicles expressed more maturation markers, such as insulin-like growth factor 1 (IGF1) and angiopoietin 1. Thus, in this chapter, granulosa cell processes and key genes were identified which may determine antral follicular developmental competence at the onset of the follicular phase.

In Chapter 4, I studied follicular developmental competence, by studying relations between follicular fluid steroid profiles and oocyte health of the presumptive ovulatory follicle pool. Sows with a high compared to a low percentage healthy COCs (<70% vs. ≥70% healthy), had higher 17β-estradiol, 19-norandrostenedione, progesterone and α-testosterone levels, while cortisol levels were lower. In addition, a larger average follicle size of the 15 largest follicles was related to higher 17β-estradiol levels. Transcriptome and selective protein analysis of granulosa cells of healthy follicles of sows with a high percentage healthy COCs showed increased expression of genes involved in steroidogenesis and follicular maturation, and a differential expression of genes regulating granulosa cell apoptosis. Also the metabolic state of the sows affected the level of COC health, as sows with a high percentage healthy COCs lost less weight during lactation and had higher serum IGF1 levels at weaning. The level of COC health at the onset of the follicular phase was thus highly related to follicular steroidogenesis.

Both follicle size and percentage healthy COCs, two follicular competence markers, were found to be related to follicular fluid steroid levels. If relations between follicular and serum steroid levels could be established, serum steroid profiles may be used to monitor follicular development. This was investigated in Chapter 5, using samples of Study 1 and 2. I identified serum steroids that reflect follicular development in the early stages of the follicular phase and established whether follicular fluid steroid levels correspond to those in serum. Serum steroid levels were never related to average follicle size of the pool. Moreover, no difference in serum steroid levels was observed when levels at the onset of the follicular phase were compared to levels in the mid-follicular phase. Serum steroid levels therefore poorly reflect the developmental stage of the follicle pool in the first half of the follicular phase of the estrous cycle and can therefore unfortunately not be used to monitor follicular development.

Another way to identify possible follicular causes of piglet birth weight and within-litter variation in birth weight, is by reducing lactational feed intake in sows. A low lactational feed intake increases mobilization of energy from body tissues which has been found to negatively influence piglet birth weight and variation in piglet birth weight of the next litter. Studying effects of lactational feed restriction on follicular and oocyte developmental competence, may therefore elucidate follicular characteristics that finally influence piglet birth weight and variation in piglet birth weight. Chapter 6 describes effects of feed restriction during the last two weeks of a 24-day lactation on follicular developmental competence at the mid-follicular phase, in primiparous sows (Study 2). Feed restriction impaired follicular developmental competence, as shown by a smaller average size of the 15 largest follicles and reduced cumulus-oocyte complex expansion after 22h in vitro maturation. Feed restriction also impaired oocyte quality, which was shown by a delayed zygote development 24h after in vitro fertilization and a higher incidence of polyspermy. This reduced follicular and oocyte developmental competence may be influenced by the lower IGF1 and steroid levels detected in the follicular fluid of restricted-fed sows. Together, these results implicate that lactational feed restriction impairs follicular steroid and growth factor production which reduces oocyte developmental competence. These impairments may at least partly explain lower piglet birth weights.

Lactational feed intake does not only affect sow performance, but also affects piglet performance by changing sow milk production, as described in Chapter 7 (Study 2). A higher feed intake during lactation resulted in a higher milk fat percentage at weaning and a higher total milk fat and protein production in the last week of lactation. Both a better body condition (higher body weight, loin muscle depth and backfat depth) at parturition and more body tissue mobilization (backfat depth loss and loin muscle depth loss) were related to a higher milk fat and/or protein production in the last week of lactation. Together, findings from Chapter 6 and 7 suggest that a higher lactational feed intake benefits both sow performance, by supporting follicular development during lactation, as well as piglet performance, by increasing sow milk production. However, more tissue mobilization during lactation impairs follicular developmental competence while it may be beneficial for milk production which supports litter weight gain. It therefore remains a challenge to design optimal feeding strategies that benefit both the current litter (sustained milk production) as well as the next litter (supporting follicular development).

In conclusion, this thesis shows that follicular developmental competence of the presumptive ovulatory follicle pool is associated with more granulosa cell differentiation and less proliferation, more steroidogenesis and a higher IGF1 production. In Chapter 8, it is argued that these identified processes may also be important for subsequent embryo and foetal survival and development, and finally, piglet birth weight and survival. The metabolic state of modern sows during lactation highly influences follicular developmental competence, already from the first half of the follicular phase onward. In addition, in primiparous modern sows, lactational weight loss influenced litter characteristics of the next litter. This provides further evidence for the hypothesis of this thesis that impairments in follicular developmental competence as established during lactation may at least partially explain the reduced reproductive performance in the next cycle and lower piglet birth weights. The degree and type of body tissue mobilization i.e. adipose tissue or lean mass, highly influences follicular development during lactation as well as milk production and composition, which are both important factors for sow performance. It seems that especially mobilization of energy from lean mass in sows with low adipose tissue reserves, negatively impacts follicular developmental competence, while mobilization of protein from lean mass may be beneficial for milk protein production to support piglet growth. It therefore remains a challenge to optimize current sow management strategies benefit sow- and piglet performance.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Keijer, Jaap, Promotor
  • Kemp, Bas, Promotor
  • Soede, Nicoline, Co-promotor
  • Teerds, Katja, Co-promotor
Award date25 Mar 2020
Place of PublicationWageningen
Publisher
Print ISBNs9789463951616
DOIs
Publication statusPublished - 2020

Keywords

  • Cum laude

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