Factors controlling epidermal growth factor (EGF) gene expression in the endometrium of the mare.

The research investigates how the hormones of pregnancy might influence the expression of the EGF gene in the endometrium of mares. The study found that progesterone can alone induce EGF expression in the endometrium, particularly after prolonged exposure.

Research Context and Methodology

• The initial observations of the research were based on EGF gene expression in pregnant mares’ endometrial glands, which was noted to increase dramatically around 40 days after ovulation.
• This study aimed to break down how the steroid hormones of pregnancy might regulate this expression thus, used in situ hybridization to monitor EGF mRNA levels in endometrial biopsies.
• These biopsies were obtained from mares during diverse hormonal states addition to different pregnancy and non-pregnancy stages and conditions: seasonally anoestrous or ovariectomised mares given exogenous progesterone and oestrogen, alone or in combination; the non-pregnant cycle; during normal pregnancies and pregnancies compromised by endometrial pathology or extraspecific embryo transfers.

Observations and Findings

• EGF expression was weak or non-existent during the late luteal phase of the oestrous cycle. However, during normal pregnancy, EGF expression was confirmed to increase dramatically after day 40 of gestation, aligning with previous observations.
• Interestingly, older mares with endometriosis and mares carrying an extraspecific donkey fetus showed the same increase in EGF mRNA in normal glands. However, this elevated EGF mRNA expression was virtually absent from glands compromised by inflammatory or fibrotic changes.

Role of Progesterone and Oestrogen in EGF Expression

• The administration of varying doses and combinations of progesterone and oestrogen for less than 35 days resulted in negative or only weakly positive EGF expression results. An interesting finding was the upregulation of EGF expression due to progesterone alone for more than or equal to 40 days which was unaffected by additional treatment with oestrogen.
• This indicates that the hormone progesterone alone can induce EGF expression, and this becomes pronounced with prolonged progesterone priming. This finding is a novelty in the field – as it presents the first experimental evidence of such influence by progesterone.
• The requirement for prolonged progesterone exposure for increased EGF expression is particularly intriguing in the context of equids, where placental attachment in pregnancy commences unusually late in the gestation period.