Ultrastructural effects of mestranol and norethindrone on guinea pig endometrial stromal cell

The effect of exogenous contraceptive steroids on the ultrstructural features of the endometrial stromal cells was studied in 64 guinea pigs allotted to 4 treatment groups. Four guinea pigs from each group were killed 14, 28, 56, and 84 days after treatment with mestranol (0.01 mg/day in 1 ml of oil) or with norethindrone (0.2 mg/day in 1 ml of oil) or with a combination of both (0.001 mg of mestranol/day and 0.02 mg of norethindrone/day in 1 ml of oil) or with 1 ml of vegetable oil (oil-treated controls). An additional 12 normal guinea pigs (nontreated controls) were killed during the follicular and luteal phases of the estrous cycle, and uterine specimens were immediately collected to determine base line characteristics. During estrus, the stromal cells of these 12 guinea pigs had abundant dilated rough endoplasmic reticulum. The interstitium was filled with collagen. During the luteal phase. the cytoplasm of the stromal cells of the 12 guinea pigs contained a prominent nucleus and rough endoplasmic reticulum with undilated cisterns. The interstitium contained sparse amounts of collagen. The stromal cells of the oil-treated control guinea pigs seemed similar in ultrastructure to the stromal cells of the 12 nontreated control guinea pigs at the luteal phase. Mestranol-fed guinea pigs had dilated rough endoplasmic reticulum and well-developed Golgi apparatus within 2 weeks of initial treatment. The interstitium of mestranol-treated guinea pigs had more collagen than that of the oil-treated controls and nontreated controls during the luteal phase. Prolonged treatment with mestranol caused extensive dilation of the cisternae of the endoplasmic reticulum. The interstitium was filled with abundant collagen. Pronounced alterations in the cytoplasmic organelles or extracellular connective tissue were not ovserved in guinea pigs given norethindrone alone or norethindrone in combination with mestranol for 14 days. The stromal cells closely resembled the cells of the mature animal at luteal phase. However, the dilated rough endoplasmic reticulum that occurred in cells after mestranol treatment was not seen in stromal cells after 84 days of treatment with norethindrone. Dilation of rough endoplasmic reticulum was also observed when both the contraceptive steroids were given simultaneously for 84 days. The increased and extensively dilated rough endoplasmic reticulum seen during the follicular phase and after mestranol administration or after 84 days of treatment with mestranol and norethindrone probably indicates increased protein synthesis by the endometrial stromal cells.