Physiological and molecular aspects of ovarian follicular developmental competence in sows

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 (