A meta-analysis: Effect of androgens on reproduction in sows

Abstract

Introduction: The mechanisms by which male hormones affect the development of ovaries and follicles has been studied by injecting exogenous androgens into sows. This may provide a reference for human polycystic ovary syndrome (PCOS), and can also provide guidance for improving the litter size of sows.

Methods: We present a meta-analysis of studies published in the past 30 years on the effect of androgens on the ovulation rate of sows. A total of 517 papers were analyzed.

Results: The results showed that both testosterone (T) and dihydrotestosterone (DHT) injected into sows were positively related to the ovulation rate. T did not have a relevant effect on swine in vivo blastocyst survival rate. DHT had a negative phase with respect to blastocyst survival rate. Pig T-androgen receiver affinity was higher than the analogous affinity for DHT; this is different in humans. This suggests that sows are not suitable as human PCOS experimental animal models.

Discussion: To improve the litter size of sows, future research should focus on the mixed use of T and DHT, and the timing of use should be consistent with the periodic changes in androgen levels in sows. In addition, the welfare of experimental sows should be considered with reference to the clinical symptoms of PCOS.

Keywords: dihydrotestosterone; oocyte; ovulation; swine; testosterone.

Figure 1

PRISMA diagram of the study selection process. The search time range was the past 30 years (1992–2022). We searched four databases: PubMed, ProQuest, ScienceDirect, and Scopus. A total of 517 relevant studies were found. The studies were divided into in vivo and in vitro categories for searching and screening. A total of 10 studies were selected for inclusion in this meta-analysis study.

Figure 2

In vivo androgen effects on sow ovary. (A) Forest plot of androgen effects on swine ovulation rate (blue) and blastocyst survival rate (white). Subgroup analysis was performed based on testosterone (T) and dihydrotestosterone (DHT). Injection of T or DHT into sows was positively related to ovulation rate. DHT was negatively correlated with blastocyst survival rate. (B) Funnel plot of androgen effects on the swine ovulation rate. The dotted vertical line is the estimated common effect. The points of the selected study representatives are concentrated at the top of the line, and there is no potential bias. (C) Trial Sequential Analysis Viewer (TSA) of androgen effects on the swine ovulation rate. The research results exceeded the conventional boundary (orange line) and monitoring boundary, indicating that the meta-analysis results are reliable. (D) Forest plot of androgen effects on the swine estrous cycle (blue) and estradiol (white). T is negatively correlated with the estrous cycle.

Figure 3

Forest plot of in vitro androgen effects on swine oocytes. The area of the green square in the figure represents the weight of each data set of the meta-analysis. The upper blue part shows the CEOs (COCs, cumulus–oocyte complexes) are negatively correlated with oocyte maturation in vitro. Denuded oocytes (DOs) are positively related to oocyte maturation. The lower white part shows that androgen (total SMD = –0.46, 95% CI= –0.70 to –0.21; p < 0.001) is negatively correlated with the in vitro swine blastocyst rate.

Figure 4

Androgen receptor protein tertiary structure and ligand docking. (A) Swine androgen receptor protein tertiary structure. The figure shows that 352 N > H, 410 P > S has no effect on NP_999479.2 (896aa) and XP_013841681.1 (896aa) tertiary structure. XP_020935172.1 (800aa) lost 96 amino acids, and the tertiary structure was altered. (B) T/DHT docking to the androgen receptor protein. The upper part shows that T and DHT docking to swine androgen receptor ligand-binding domain (sARLBD) is the same. To show the connecting bridges, the observation direction has been adjusted. The middle part is the local amplification of the ligand-binding pocket (LBP). The lower part shows the binding affinity.

Figure 5

Proposed mode of androgens effect on sow reproduction. The green arrow indicates improvement. The red flat-end segment represents a decrease. The left side indicates that T/DHT promotes pig ovulation in vivo. T/DHT inhibits COCs in vitro maturation and promotes DOs maturation. The right side shows that human T inhibits the development of antral follicles to mature follicles.